DK2348827T3 - Immunkompromitterede hovdyr - Google Patents
Immunkompromitterede hovdyr Download PDFInfo
- Publication number
- DK2348827T3 DK2348827T3 DK09824080.7T DK09824080T DK2348827T3 DK 2348827 T3 DK2348827 T3 DK 2348827T3 DK 09824080 T DK09824080 T DK 09824080T DK 2348827 T3 DK2348827 T3 DK 2348827T3
- Authority
- DK
- Denmark
- Prior art keywords
- cells
- gene
- pig
- cell
- vol
- Prior art date
Links
- 241001465754 Metazoa Species 0.000 claims description 243
- 108090000623 proteins and genes Proteins 0.000 claims description 208
- 241000282887 Suidae Species 0.000 claims description 114
- 108060003951 Immunoglobulin Proteins 0.000 claims description 109
- 102000018358 immunoglobulin Human genes 0.000 claims description 109
- 238000000034 method Methods 0.000 claims description 108
- 210000003719 b-lymphocyte Anatomy 0.000 claims description 94
- 241000282898 Sus scrofa Species 0.000 claims description 86
- 230000014509 gene expression Effects 0.000 claims description 69
- 108700005091 Immunoglobulin Genes Proteins 0.000 claims description 59
- 239000000427 antigen Substances 0.000 claims description 41
- 108091007433 antigens Proteins 0.000 claims description 41
- 102000036639 antigens Human genes 0.000 claims description 41
- 239000012634 fragment Substances 0.000 claims description 39
- 238000004519 manufacturing process Methods 0.000 claims description 38
- 208000015181 infectious disease Diseases 0.000 claims description 37
- 108700028369 Alleles Proteins 0.000 claims description 34
- 239000003814 drug Substances 0.000 claims description 24
- 102000004169 proteins and genes Human genes 0.000 claims description 24
- 230000004044 response Effects 0.000 claims description 20
- 230000028993 immune response Effects 0.000 claims description 19
- 229960005486 vaccine Drugs 0.000 claims description 18
- 238000012217 deletion Methods 0.000 claims description 17
- 230000037430 deletion Effects 0.000 claims description 17
- 239000012678 infectious agent Substances 0.000 claims description 14
- 241000700605 Viruses Species 0.000 claims description 12
- 108700019146 Transgenes Proteins 0.000 claims description 11
- 230000002829 reductive effect Effects 0.000 claims description 11
- 230000024932 T cell mediated immunity Effects 0.000 claims description 7
- 230000000903 blocking effect Effects 0.000 claims description 7
- 230000000069 prophylactic effect Effects 0.000 claims description 7
- 230000007812 deficiency Effects 0.000 claims description 6
- 238000010998 test method Methods 0.000 claims description 6
- 230000000139 costimulatory effect Effects 0.000 claims description 5
- 229940045513 CTLA4 antagonist Drugs 0.000 claims description 4
- 230000036755 cellular response Effects 0.000 claims description 4
- 230000008348 humoral response Effects 0.000 claims description 4
- 229940124597 therapeutic agent Drugs 0.000 claims description 4
- 102100039498 Cytotoxic T-lymphocyte protein 4 Human genes 0.000 claims 3
- 101000889276 Homo sapiens Cytotoxic T-lymphocyte protein 4 Proteins 0.000 claims 3
- 210000004027 cell Anatomy 0.000 description 263
- 210000004507 artificial chromosome Anatomy 0.000 description 82
- 108020004414 DNA Proteins 0.000 description 74
- 239000013598 vector Substances 0.000 description 65
- 210000001744 T-lymphocyte Anatomy 0.000 description 57
- 230000002950 deficient Effects 0.000 description 54
- 210000000349 chromosome Anatomy 0.000 description 52
- 210000000287 oocyte Anatomy 0.000 description 52
- 230000008685 targeting Effects 0.000 description 51
- 238000012546 transfer Methods 0.000 description 48
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 40
- 230000006798 recombination Effects 0.000 description 40
- 238000005215 recombination Methods 0.000 description 40
- 230000009261 transgenic effect Effects 0.000 description 37
- 241000699666 Mus <mouse, genus> Species 0.000 description 36
- 241000699670 Mus sp. Species 0.000 description 36
- 241000282412 Homo Species 0.000 description 32
- 201000010099 disease Diseases 0.000 description 29
- 238000010171 animal model Methods 0.000 description 28
- 150000007523 nucleic acids Chemical class 0.000 description 28
- 238000011160 research Methods 0.000 description 28
- 230000008707 rearrangement Effects 0.000 description 27
- 102000039446 nucleic acids Human genes 0.000 description 25
- 108020004707 nucleic acids Proteins 0.000 description 25
- 238000004458 analytical method Methods 0.000 description 24
- 238000012239 gene modification Methods 0.000 description 24
- 230000005017 genetic modification Effects 0.000 description 24
- 235000013617 genetically modified food Nutrition 0.000 description 24
- 238000011161 development Methods 0.000 description 23
- 230000018109 developmental process Effects 0.000 description 23
- 230000035772 mutation Effects 0.000 description 23
- 238000011282 treatment Methods 0.000 description 23
- 210000002966 serum Anatomy 0.000 description 22
- 241000894007 species Species 0.000 description 22
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 21
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 21
- 210000002950 fibroblast Anatomy 0.000 description 21
- 238000005304 joining Methods 0.000 description 21
- 210000001165 lymph node Anatomy 0.000 description 21
- 238000003752 polymerase chain reaction Methods 0.000 description 21
- 210000001519 tissue Anatomy 0.000 description 21
- 238000002744 homologous recombination Methods 0.000 description 20
- 230000006801 homologous recombination Effects 0.000 description 20
- 210000004698 lymphocyte Anatomy 0.000 description 20
- 230000010354 integration Effects 0.000 description 19
- 101100454807 Caenorhabditis elegans lgg-1 gene Proteins 0.000 description 18
- 239000003550 marker Substances 0.000 description 18
- 230000001717 pathogenic effect Effects 0.000 description 18
- 102000008203 CTLA-4 Antigen Human genes 0.000 description 16
- 108010021064 CTLA-4 Antigen Proteins 0.000 description 16
- 230000007246 mechanism Effects 0.000 description 16
- 244000052769 pathogen Species 0.000 description 16
- 239000003795 chemical substances by application Substances 0.000 description 15
- 230000036039 immunity Effects 0.000 description 15
- 238000012360 testing method Methods 0.000 description 15
- 241000283973 Oryctolagus cuniculus Species 0.000 description 14
- 108010052160 Site-specific recombinase Proteins 0.000 description 14
- 238000010367 cloning Methods 0.000 description 14
- 210000001161 mammalian embryo Anatomy 0.000 description 14
- 230000001404 mediated effect Effects 0.000 description 14
- 108090000765 processed proteins & peptides Proteins 0.000 description 14
- 238000010186 staining Methods 0.000 description 14
- 108010091086 Recombinases Proteins 0.000 description 13
- 102000018120 Recombinases Human genes 0.000 description 13
- 230000004913 activation Effects 0.000 description 13
- 210000002230 centromere Anatomy 0.000 description 13
- 230000001605 fetal effect Effects 0.000 description 13
- 238000010363 gene targeting Methods 0.000 description 13
- 210000004602 germ cell Anatomy 0.000 description 13
- 210000001280 germinal center Anatomy 0.000 description 13
- 230000004048 modification Effects 0.000 description 13
- 238000012986 modification Methods 0.000 description 13
- 241000283690 Bos taurus Species 0.000 description 12
- 238000002105 Southern blotting Methods 0.000 description 12
- 210000001671 embryonic stem cell Anatomy 0.000 description 12
- 210000003754 fetus Anatomy 0.000 description 12
- 210000003917 human chromosome Anatomy 0.000 description 12
- 229940072221 immunoglobulins Drugs 0.000 description 12
- 238000002347 injection Methods 0.000 description 12
- 239000007924 injection Substances 0.000 description 12
- 210000000056 organ Anatomy 0.000 description 12
- 239000013612 plasmid Substances 0.000 description 12
- 108091028043 Nucleic acid sequence Proteins 0.000 description 11
- 208000035475 disorder Diseases 0.000 description 11
- 230000004927 fusion Effects 0.000 description 11
- 238000012872 hydroxylapatite chromatography Methods 0.000 description 11
- 238000003780 insertion Methods 0.000 description 11
- 210000000265 leukocyte Anatomy 0.000 description 11
- 230000007170 pathology Effects 0.000 description 11
- 238000010374 somatic cell nuclear transfer Methods 0.000 description 11
- 230000001225 therapeutic effect Effects 0.000 description 11
- 208000035473 Communicable disease Diseases 0.000 description 10
- 102100023371 Forkhead box protein N1 Human genes 0.000 description 10
- 101000907576 Homo sapiens Forkhead box protein N1 Proteins 0.000 description 10
- 238000000338 in vitro Methods 0.000 description 10
- 230000010076 replication Effects 0.000 description 10
- 238000013518 transcription Methods 0.000 description 10
- 230000035897 transcription Effects 0.000 description 10
- 102000011022 Chorionic Gonadotropin Human genes 0.000 description 9
- 108010062540 Chorionic Gonadotropin Proteins 0.000 description 9
- 201000003883 Cystic fibrosis Diseases 0.000 description 9
- 241000283984 Rodentia Species 0.000 description 9
- 108700022368 Whn Proteins 0.000 description 9
- 210000004436 artificial bacterial chromosome Anatomy 0.000 description 9
- 238000009395 breeding Methods 0.000 description 9
- 230000001488 breeding effect Effects 0.000 description 9
- 229940079593 drug Drugs 0.000 description 9
- 210000002257 embryonic structure Anatomy 0.000 description 9
- 210000002919 epithelial cell Anatomy 0.000 description 9
- 229940084986 human chorionic gonadotropin Drugs 0.000 description 9
- 230000001900 immune effect Effects 0.000 description 9
- 230000037431 insertion Effects 0.000 description 9
- 210000004962 mammalian cell Anatomy 0.000 description 9
- 239000002609 medium Substances 0.000 description 9
- 230000035935 pregnancy Effects 0.000 description 9
- 230000008569 process Effects 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- 230000003612 virological effect Effects 0.000 description 9
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 description 8
- 206010061598 Immunodeficiency Diseases 0.000 description 8
- 101100067103 Mus musculus Foxn1 gene Proteins 0.000 description 8
- 102000001183 RAG-1 Human genes 0.000 description 8
- 108060006897 RAG1 Proteins 0.000 description 8
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 description 8
- 230000004075 alteration Effects 0.000 description 8
- 230000027455 binding Effects 0.000 description 8
- 230000001413 cellular effect Effects 0.000 description 8
- 238000000684 flow cytometry Methods 0.000 description 8
- 230000028996 humoral immune response Effects 0.000 description 8
- 208000024191 minimally invasive lung adenocarcinoma Diseases 0.000 description 8
- 238000003757 reverse transcription PCR Methods 0.000 description 8
- 238000001890 transfection Methods 0.000 description 8
- 241000894006 Bacteria Species 0.000 description 7
- 241000283707 Capra Species 0.000 description 7
- 241000287828 Gallus gallus Species 0.000 description 7
- 101150008942 J gene Proteins 0.000 description 7
- 230000005867 T cell response Effects 0.000 description 7
- 210000000612 antigen-presenting cell Anatomy 0.000 description 7
- 235000013330 chicken meat Nutrition 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 230000003325 follicular Effects 0.000 description 7
- 238000001727 in vivo Methods 0.000 description 7
- 230000031864 metaphase Effects 0.000 description 7
- 238000012216 screening Methods 0.000 description 7
- 238000002054 transplantation Methods 0.000 description 7
- 102000004190 Enzymes Human genes 0.000 description 6
- 108090000790 Enzymes Proteins 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 241001494479 Pecora Species 0.000 description 6
- 208000005342 Porcine Reproductive and Respiratory Syndrome Diseases 0.000 description 6
- 241001135989 Porcine reproductive and respiratory syndrome virus Species 0.000 description 6
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 6
- 206010042602 Supraventricular extrasystoles Diseases 0.000 description 6
- 101150117115 V gene Proteins 0.000 description 6
- 108010032099 V(D)J recombination activating protein 2 Proteins 0.000 description 6
- 208000035472 Zoonoses Diseases 0.000 description 6
- 230000003321 amplification Effects 0.000 description 6
- 238000013459 approach Methods 0.000 description 6
- 238000012512 characterization method Methods 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 230000000295 complement effect Effects 0.000 description 6
- 238000012258 culturing Methods 0.000 description 6
- 238000010790 dilution Methods 0.000 description 6
- 239000012895 dilution Substances 0.000 description 6
- 230000007159 enucleation Effects 0.000 description 6
- 229940088598 enzyme Drugs 0.000 description 6
- 238000012423 maintenance Methods 0.000 description 6
- 230000035800 maturation Effects 0.000 description 6
- 238000003199 nucleic acid amplification method Methods 0.000 description 6
- 239000002773 nucleotide Substances 0.000 description 6
- 125000003729 nucleotide group Chemical group 0.000 description 6
- 210000004940 nucleus Anatomy 0.000 description 6
- 108020003175 receptors Proteins 0.000 description 6
- 102000005962 receptors Human genes 0.000 description 6
- 229940050570 regu-mate Drugs 0.000 description 6
- 238000012552 review Methods 0.000 description 6
- 239000000523 sample Substances 0.000 description 6
- 210000000952 spleen Anatomy 0.000 description 6
- 206010048282 zoonosis Diseases 0.000 description 6
- 208000035143 Bacterial infection Diseases 0.000 description 5
- 108091026890 Coding region Proteins 0.000 description 5
- 101100193633 Danio rerio rag2 gene Proteins 0.000 description 5
- 238000002965 ELISA Methods 0.000 description 5
- 241000588724 Escherichia coli Species 0.000 description 5
- 102000006496 Immunoglobulin Heavy Chains Human genes 0.000 description 5
- 108010019476 Immunoglobulin Heavy Chains Proteins 0.000 description 5
- 241000699660 Mus musculus Species 0.000 description 5
- 101100193635 Mus musculus Rag2 gene Proteins 0.000 description 5
- 238000011887 Necropsy Methods 0.000 description 5
- 241001429055 Nora virus Species 0.000 description 5
- 241000700159 Rattus Species 0.000 description 5
- 241000702670 Rotavirus Species 0.000 description 5
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 5
- 108091023040 Transcription factor Proteins 0.000 description 5
- 102000040945 Transcription factor Human genes 0.000 description 5
- 230000003115 biocidal effect Effects 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 210000002459 blastocyst Anatomy 0.000 description 5
- 210000004369 blood Anatomy 0.000 description 5
- 239000008280 blood Substances 0.000 description 5
- 239000002299 complementary DNA Substances 0.000 description 5
- 238000010276 construction Methods 0.000 description 5
- 239000012636 effector Substances 0.000 description 5
- 230000006870 function Effects 0.000 description 5
- 230000002068 genetic effect Effects 0.000 description 5
- 210000002216 heart Anatomy 0.000 description 5
- 230000000977 initiatory effect Effects 0.000 description 5
- 239000012528 membrane Substances 0.000 description 5
- 230000011278 mitosis Effects 0.000 description 5
- 238000010172 mouse model Methods 0.000 description 5
- 230000008520 organization Effects 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 210000001082 somatic cell Anatomy 0.000 description 5
- 230000000392 somatic effect Effects 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 108091035539 telomere Proteins 0.000 description 5
- 210000003411 telomere Anatomy 0.000 description 5
- 102000055501 telomere Human genes 0.000 description 5
- 238000002689 xenotransplantation Methods 0.000 description 5
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 4
- 108010013423 CMPacetylneuraminate monooxygenase Proteins 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 108010051219 Cre recombinase Proteins 0.000 description 4
- 101150097493 D gene Proteins 0.000 description 4
- 108010067770 Endopeptidase K Proteins 0.000 description 4
- 241000283074 Equus asinus Species 0.000 description 4
- 241000702191 Escherichia virus P1 Species 0.000 description 4
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 4
- 108060003306 Galactosyltransferase Proteins 0.000 description 4
- 102000030902 Galactosyltransferase Human genes 0.000 description 4
- 108010091714 Globoside alpha-N-acetylgalactosaminyltransferase Proteins 0.000 description 4
- 101000897400 Homo sapiens CD59 glycoprotein Proteins 0.000 description 4
- 241000617996 Human rotavirus Species 0.000 description 4
- 102000013463 Immunoglobulin Light Chains Human genes 0.000 description 4
- 108010065825 Immunoglobulin Light Chains Proteins 0.000 description 4
- 241000124008 Mammalia Species 0.000 description 4
- 241000255969 Pieris brassicae Species 0.000 description 4
- 241000288906 Primates Species 0.000 description 4
- 108091034057 RNA (poly(A)) Proteins 0.000 description 4
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 4
- 210000004102 animal cell Anatomy 0.000 description 4
- 210000003022 colostrum Anatomy 0.000 description 4
- 235000021277 colostrum Nutrition 0.000 description 4
- 210000000805 cytoplasm Anatomy 0.000 description 4
- 238000004520 electroporation Methods 0.000 description 4
- 210000003743 erythrocyte Anatomy 0.000 description 4
- 239000012894 fetal calf serum Substances 0.000 description 4
- 210000001035 gastrointestinal tract Anatomy 0.000 description 4
- 239000001963 growth medium Substances 0.000 description 4
- 210000003128 head Anatomy 0.000 description 4
- 238000003125 immunofluorescent labeling Methods 0.000 description 4
- 230000002998 immunogenetic effect Effects 0.000 description 4
- 210000003563 lymphoid tissue Anatomy 0.000 description 4
- 210000002540 macrophage Anatomy 0.000 description 4
- 230000008774 maternal effect Effects 0.000 description 4
- 108020004999 messenger RNA Proteins 0.000 description 4
- 238000000520 microinjection Methods 0.000 description 4
- 238000010369 molecular cloning Methods 0.000 description 4
- 210000001616 monocyte Anatomy 0.000 description 4
- 238000011580 nude mouse model Methods 0.000 description 4
- 210000000496 pancreas Anatomy 0.000 description 4
- 238000013310 pig model Methods 0.000 description 4
- 239000002243 precursor Substances 0.000 description 4
- 102000004196 processed proteins & peptides Human genes 0.000 description 4
- 230000001681 protective effect Effects 0.000 description 4
- 238000010561 standard procedure Methods 0.000 description 4
- 239000000758 substrate Substances 0.000 description 4
- 201000010740 swine influenza Diseases 0.000 description 4
- 241001515965 unidentified phage Species 0.000 description 4
- 238000011144 upstream manufacturing Methods 0.000 description 4
- 230000001018 virulence Effects 0.000 description 4
- 238000001262 western blot Methods 0.000 description 4
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 4
- 206010069754 Acquired gene mutation Diseases 0.000 description 3
- 206010003445 Ascites Diseases 0.000 description 3
- 208000023275 Autoimmune disease Diseases 0.000 description 3
- 102100022002 CD59 glycoprotein Human genes 0.000 description 3
- 241001550206 Colla Species 0.000 description 3
- 102000004127 Cytokines Human genes 0.000 description 3
- 108090000695 Cytokines Proteins 0.000 description 3
- -1 DAF Proteins 0.000 description 3
- 230000004568 DNA-binding Effects 0.000 description 3
- 108010046276 FLP recombinase Proteins 0.000 description 3
- 108010019236 Fucosyltransferases Proteins 0.000 description 3
- 102000006471 Fucosyltransferases Human genes 0.000 description 3
- 108700028146 Genetic Enhancer Elements Proteins 0.000 description 3
- 101100067102 Homo sapiens FOXN1 gene Proteins 0.000 description 3
- 101000961414 Homo sapiens Membrane cofactor protein Proteins 0.000 description 3
- 206010020751 Hypersensitivity Diseases 0.000 description 3
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 3
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- 108700018351 Major Histocompatibility Complex Proteins 0.000 description 3
- 102100039373 Membrane cofactor protein Human genes 0.000 description 3
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 3
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 3
- 102000003838 Sialyltransferases Human genes 0.000 description 3
- 108090000141 Sialyltransferases Proteins 0.000 description 3
- 230000006044 T cell activation Effects 0.000 description 3
- 108091008874 T cell receptors Proteins 0.000 description 3
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 3
- 239000007983 Tris buffer Substances 0.000 description 3
- 108010078334 UDP-galactose beta-D-galactosyl-1,4-glycosylceramide alpha-1,3-galactosyltransferase Proteins 0.000 description 3
- 102100029591 V(D)J recombination-activating protein 2 Human genes 0.000 description 3
- 230000001154 acute effect Effects 0.000 description 3
- 230000007815 allergy Effects 0.000 description 3
- 150000001413 amino acids Chemical group 0.000 description 3
- 239000003242 anti bacterial agent Substances 0.000 description 3
- 230000001580 bacterial effect Effects 0.000 description 3
- 208000022362 bacterial infectious disease Diseases 0.000 description 3
- 244000052616 bacterial pathogen Species 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 210000004413 cardiac myocyte Anatomy 0.000 description 3
- 230000015556 catabolic process Effects 0.000 description 3
- 150000001768 cations Chemical class 0.000 description 3
- 210000001612 chondrocyte Anatomy 0.000 description 3
- 210000001771 cumulus cell Anatomy 0.000 description 3
- 230000009089 cytolysis Effects 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- 238000013461 design Methods 0.000 description 3
- 238000001962 electrophoresis Methods 0.000 description 3
- 210000002889 endothelial cell Anatomy 0.000 description 3
- 239000003623 enhancer Substances 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 239000013604 expression vector Substances 0.000 description 3
- 230000004720 fertilization Effects 0.000 description 3
- 210000000285 follicular dendritic cell Anatomy 0.000 description 3
- 230000008217 follicular development Effects 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- 239000003102 growth factor Substances 0.000 description 3
- 229940088597 hormone Drugs 0.000 description 3
- 239000005556 hormone Substances 0.000 description 3
- 230000004727 humoral immunity Effects 0.000 description 3
- 210000000987 immune system Anatomy 0.000 description 3
- 238000010166 immunofluorescence Methods 0.000 description 3
- 230000016784 immunoglobulin production Effects 0.000 description 3
- 206010022000 influenza Diseases 0.000 description 3
- 230000000968 intestinal effect Effects 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 238000002955 isolation Methods 0.000 description 3
- 210000002510 keratinocyte Anatomy 0.000 description 3
- 210000003734 kidney Anatomy 0.000 description 3
- 239000003446 ligand Substances 0.000 description 3
- 210000004185 liver Anatomy 0.000 description 3
- 210000004072 lung Anatomy 0.000 description 3
- 206010025135 lupus erythematosus Diseases 0.000 description 3
- 239000006166 lysate Substances 0.000 description 3
- 201000004792 malaria Diseases 0.000 description 3
- 230000008219 male gametogenesis Effects 0.000 description 3
- 210000004379 membrane Anatomy 0.000 description 3
- 230000000813 microbial effect Effects 0.000 description 3
- 230000000394 mitotic effect Effects 0.000 description 3
- 210000000663 muscle cell Anatomy 0.000 description 3
- 210000001672 ovary Anatomy 0.000 description 3
- 210000003101 oviduct Anatomy 0.000 description 3
- 230000026731 phosphorylation Effects 0.000 description 3
- 238000006366 phosphorylation reaction Methods 0.000 description 3
- 210000004508 polar body Anatomy 0.000 description 3
- 238000011084 recovery Methods 0.000 description 3
- 108091008146 restriction endonucleases Proteins 0.000 description 3
- 238000011808 rodent model Methods 0.000 description 3
- 238000012163 sequencing technique Methods 0.000 description 3
- 230000035939 shock Effects 0.000 description 3
- 210000003491 skin Anatomy 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 230000037439 somatic mutation Effects 0.000 description 3
- 210000000130 stem cell Anatomy 0.000 description 3
- 230000000638 stimulation Effects 0.000 description 3
- 230000020382 suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I Effects 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 238000011830 transgenic mouse model Methods 0.000 description 3
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 3
- 244000052613 viral pathogen Species 0.000 description 3
- 210000005253 yeast cell Anatomy 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 2
- VWAUPFMBXBWEQY-ANULTFPQSA-N Altrenogest Chemical compound C1CC(=O)C=C2CC[C@@H]([C@H]3[C@@](C)([C@](CC3)(O)CC=C)C=C3)C3=C21 VWAUPFMBXBWEQY-ANULTFPQSA-N 0.000 description 2
- 230000003844 B-cell-activation Effects 0.000 description 2
- 241000282817 Bovidae Species 0.000 description 2
- 108010067225 Cell Adhesion Molecules Proteins 0.000 description 2
- 241000282994 Cervidae Species 0.000 description 2
- 208000037088 Chromosome Breakage Diseases 0.000 description 2
- 241000699800 Cricetinae Species 0.000 description 2
- 102000053602 DNA Human genes 0.000 description 2
- 230000004543 DNA replication Effects 0.000 description 2
- 206010012735 Diarrhoea Diseases 0.000 description 2
- SHIBSTMRCDJXLN-UHFFFAOYSA-N Digoxigenin Natural products C1CC(C2C(C3(C)CCC(O)CC3CC2)CC2O)(O)C2(C)C1C1=CC(=O)OC1 SHIBSTMRCDJXLN-UHFFFAOYSA-N 0.000 description 2
- 241001397104 Dima Species 0.000 description 2
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- 238000012286 ELISA Assay Methods 0.000 description 2
- 108091029865 Exogenous DNA Proteins 0.000 description 2
- 108700024394 Exon Proteins 0.000 description 2
- 102000003974 Fibroblast growth factor 2 Human genes 0.000 description 2
- 108090000379 Fibroblast growth factor 2 Proteins 0.000 description 2
- 102000051366 Glycosyltransferases Human genes 0.000 description 2
- 108700023372 Glycosyltransferases Proteins 0.000 description 2
- 206010069767 H1N1 influenza Diseases 0.000 description 2
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 2
- 101100246753 Halobacterium salinarum (strain ATCC 700922 / JCM 11081 / NRC-1) pyrF gene Proteins 0.000 description 2
- 239000012981 Hank's balanced salt solution Substances 0.000 description 2
- 241000238631 Hexapoda Species 0.000 description 2
- 101000914484 Homo sapiens T-lymphocyte activation antigen CD80 Proteins 0.000 description 2
- 108010003272 Hyaluronate lyase Proteins 0.000 description 2
- 102000001974 Hyaluronidases Human genes 0.000 description 2
- 241000712431 Influenza A virus Species 0.000 description 2
- 108010061833 Integrases Proteins 0.000 description 2
- 108090001090 Lectins Proteins 0.000 description 2
- 102000004856 Lectins Human genes 0.000 description 2
- 241000222722 Leishmania <genus> Species 0.000 description 2
- 101100343701 Mus musculus Loxl1 gene Proteins 0.000 description 2
- BVIAOQMSVZHOJM-UHFFFAOYSA-N N(6),N(6)-dimethyladenine Chemical compound CN(C)C1=NC=NC2=C1N=CN2 BVIAOQMSVZHOJM-UHFFFAOYSA-N 0.000 description 2
- 108091061960 Naked DNA Proteins 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 238000010222 PCR analysis Methods 0.000 description 2
- 208000030852 Parasitic disease Diseases 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 101710186910 Putative pterin-4-alpha-carbinolamine dehydratase 2 Proteins 0.000 description 2
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 2
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 2
- 238000011579 SCID mouse model Methods 0.000 description 2
- 241000607142 Salmonella Species 0.000 description 2
- 241001138501 Salmonella enterica Species 0.000 description 2
- 241000293869 Salmonella enterica subsp. enterica serovar Typhimurium Species 0.000 description 2
- 241000369757 Sapovirus Species 0.000 description 2
- 206010040047 Sepsis Diseases 0.000 description 2
- 201000003176 Severe Acute Respiratory Syndrome Diseases 0.000 description 2
- 241000607762 Shigella flexneri Species 0.000 description 2
- 108010090804 Streptavidin Proteins 0.000 description 2
- 239000004098 Tetracycline Substances 0.000 description 2
- 108010020764 Transposases Proteins 0.000 description 2
- 102000008579 Transposases Human genes 0.000 description 2
- 101150050575 URA3 gene Proteins 0.000 description 2
- 241000700647 Variola virus Species 0.000 description 2
- 208000036142 Viral infection Diseases 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 208000026935 allergic disease Diseases 0.000 description 2
- 229960000971 altrenogest Drugs 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- 210000000628 antibody-producing cell Anatomy 0.000 description 2
- 230000000890 antigenic effect Effects 0.000 description 2
- 210000001106 artificial yeast chromosome Anatomy 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000005540 biological transmission Effects 0.000 description 2
- 229960002685 biotin Drugs 0.000 description 2
- 239000011616 biotin Substances 0.000 description 2
- 239000010836 blood and blood product Substances 0.000 description 2
- 210000000601 blood cell Anatomy 0.000 description 2
- 210000001772 blood platelet Anatomy 0.000 description 2
- 229940125691 blood product Drugs 0.000 description 2
- 210000004204 blood vessel Anatomy 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 230000018486 cell cycle phase Effects 0.000 description 2
- 210000000170 cell membrane Anatomy 0.000 description 2
- 210000003855 cell nucleus Anatomy 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000013611 chromosomal DNA Substances 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 230000001010 compromised effect Effects 0.000 description 2
- 230000004940 costimulation Effects 0.000 description 2
- 101150036876 cre gene Proteins 0.000 description 2
- 238000012864 cross contamination Methods 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 230000000779 depleting effect Effects 0.000 description 2
- 230000000994 depressogenic effect Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- 229910003460 diamond Inorganic materials 0.000 description 2
- 239000010432 diamond Substances 0.000 description 2
- 235000005911 diet Nutrition 0.000 description 2
- 230000000378 dietary effect Effects 0.000 description 2
- 235000020930 dietary requirements Nutrition 0.000 description 2
- QONQRTHLHBTMGP-UHFFFAOYSA-N digitoxigenin Natural products CC12CCC(C3(CCC(O)CC3CC3)C)C3C11OC1CC2C1=CC(=O)OC1 QONQRTHLHBTMGP-UHFFFAOYSA-N 0.000 description 2
- SHIBSTMRCDJXLN-KCZCNTNESA-N digoxigenin Chemical compound C1([C@@H]2[C@@]3([C@@](CC2)(O)[C@H]2[C@@H]([C@@]4(C)CC[C@H](O)C[C@H]4CC2)C[C@H]3O)C)=CC(=O)OC1 SHIBSTMRCDJXLN-KCZCNTNESA-N 0.000 description 2
- 230000003292 diminished effect Effects 0.000 description 2
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 2
- 231100000676 disease causative agent Toxicity 0.000 description 2
- 230000003828 downregulation Effects 0.000 description 2
- 235000013601 eggs Nutrition 0.000 description 2
- 238000001493 electron microscopy Methods 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 108010048367 enhanced green fluorescent protein Proteins 0.000 description 2
- 210000001339 epidermal cell Anatomy 0.000 description 2
- 230000012173 estrus Effects 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 230000035558 fertility Effects 0.000 description 2
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 2
- 230000036397 gastrointestinal physiology Effects 0.000 description 2
- 238000003205 genotyping method Methods 0.000 description 2
- 102000018146 globin Human genes 0.000 description 2
- 108060003196 globin Proteins 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 2
- 201000010284 hepatitis E Diseases 0.000 description 2
- 210000000688 human artificial chromosome Anatomy 0.000 description 2
- 244000052637 human pathogen Species 0.000 description 2
- 229960002773 hyaluronidase Drugs 0.000 description 2
- 230000036737 immune function Effects 0.000 description 2
- 238000003364 immunohistochemistry Methods 0.000 description 2
- 230000001771 impaired effect Effects 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 230000002458 infectious effect Effects 0.000 description 2
- 208000027866 inflammatory disease Diseases 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 239000012212 insulator Substances 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 210000000936 intestine Anatomy 0.000 description 2
- 210000004153 islets of langerhan Anatomy 0.000 description 2
- 229940043355 kinase inhibitor Drugs 0.000 description 2
- 101150066555 lacZ gene Proteins 0.000 description 2
- 239000002523 lectin Substances 0.000 description 2
- 231100000518 lethal Toxicity 0.000 description 2
- 230000001665 lethal effect Effects 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- 210000000723 mammalian artificial chromosome Anatomy 0.000 description 2
- 210000003519 mature b lymphocyte Anatomy 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 210000002752 melanocyte Anatomy 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 210000005087 mononuclear cell Anatomy 0.000 description 2
- 210000000822 natural killer cell Anatomy 0.000 description 2
- 229960004927 neomycin Drugs 0.000 description 2
- 210000003061 neural cell Anatomy 0.000 description 2
- 229940035567 orencia Drugs 0.000 description 2
- 230000002018 overexpression Effects 0.000 description 2
- 230000008506 pathogenesis Effects 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- 210000001986 peyer's patch Anatomy 0.000 description 2
- 239000002953 phosphate buffered saline Substances 0.000 description 2
- 239000003757 phosphotransferase inhibitor Substances 0.000 description 2
- 230000006461 physiological response Effects 0.000 description 2
- 230000000644 propagated effect Effects 0.000 description 2
- 238000011321 prophylaxis Methods 0.000 description 2
- 230000005180 public health Effects 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- RXWNCPJZOCPEPQ-NVWDDTSBSA-N puromycin Chemical compound C1=CC(OC)=CC=C1C[C@H](N)C(=O)N[C@H]1[C@@H](O)[C@H](N2C3=NC=NC(=C3N=C2)N(C)C)O[C@@H]1CO RXWNCPJZOCPEPQ-NVWDDTSBSA-N 0.000 description 2
- 230000003362 replicative effect Effects 0.000 description 2
- 230000001850 reproductive effect Effects 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 208000013223 septicemia Diseases 0.000 description 2
- BAZAXWOYCMUHIX-UHFFFAOYSA-M sodium perchlorate Chemical compound [Na+].[O-]Cl(=O)(=O)=O BAZAXWOYCMUHIX-UHFFFAOYSA-M 0.000 description 2
- 229910001488 sodium perchlorate Inorganic materials 0.000 description 2
- DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 2
- 230000003393 splenic effect Effects 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 230000001360 synchronised effect Effects 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 229960002180 tetracycline Drugs 0.000 description 2
- 229930101283 tetracycline Natural products 0.000 description 2
- 235000019364 tetracycline Nutrition 0.000 description 2
- 150000003522 tetracyclines Chemical class 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 239000003053 toxin Substances 0.000 description 2
- 231100000765 toxin Toxicity 0.000 description 2
- 108700012359 toxins Proteins 0.000 description 2
- 238000010361 transduction Methods 0.000 description 2
- 230000026683 transduction Effects 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- 230000001052 transient effect Effects 0.000 description 2
- 210000003708 urethra Anatomy 0.000 description 2
- 210000003932 urinary bladder Anatomy 0.000 description 2
- 210000004291 uterus Anatomy 0.000 description 2
- 238000002255 vaccination Methods 0.000 description 2
- 230000009385 viral infection Effects 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 244000000023 zoonotic pathogen Species 0.000 description 2
- WWUZIQQURGPMPG-UHFFFAOYSA-N (-)-D-erythro-Sphingosine Natural products CCCCCCCCCCCCCC=CC(O)C(N)CO WWUZIQQURGPMPG-UHFFFAOYSA-N 0.000 description 1
- AYIRNRDRBQJXIF-NXEZZACHSA-N (-)-Florfenicol Chemical compound CS(=O)(=O)C1=CC=C([C@@H](O)[C@@H](CF)NC(=O)C(Cl)Cl)C=C1 AYIRNRDRBQJXIF-NXEZZACHSA-N 0.000 description 1
- BHNQPLPANNDEGL-UHFFFAOYSA-N 2-(4-octylphenoxy)ethanol Chemical compound CCCCCCCCC1=CC=C(OCCO)C=C1 BHNQPLPANNDEGL-UHFFFAOYSA-N 0.000 description 1
- MWBWWFOAEOYUST-UHFFFAOYSA-N 2-aminopurine Chemical compound NC1=NC=C2N=CNC2=N1 MWBWWFOAEOYUST-UHFFFAOYSA-N 0.000 description 1
- 101150098072 20 gene Proteins 0.000 description 1
- 108020005065 3' Flanking Region Proteins 0.000 description 1
- 238000013030 3-step procedure Methods 0.000 description 1
- FWBHETKCLVMNFS-UHFFFAOYSA-N 4',6-Diamino-2-phenylindol Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC2=CC=C(C(N)=N)C=C2N1 FWBHETKCLVMNFS-UHFFFAOYSA-N 0.000 description 1
- 108020005029 5' Flanking Region Proteins 0.000 description 1
- OPIFSICVWOWJMJ-AEOCFKNESA-N 5-bromo-4-chloro-3-indolyl beta-D-galactoside Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1OC1=CNC2=CC=C(Br)C(Cl)=C12 OPIFSICVWOWJMJ-AEOCFKNESA-N 0.000 description 1
- WOVKYSAHUYNSMH-RRKCRQDMSA-N 5-bromodeoxyuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(Br)=C1 WOVKYSAHUYNSMH-RRKCRQDMSA-N 0.000 description 1
- 241000251468 Actinopterygii Species 0.000 description 1
- 206010001258 Adenoviral infections Diseases 0.000 description 1
- 208000008190 Agammaglobulinemia Diseases 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- 241000380131 Ammophila arenaria Species 0.000 description 1
- 108091093088 Amplicon Proteins 0.000 description 1
- 244000144725 Amygdalus communis Species 0.000 description 1
- 235000011437 Amygdalus communis Nutrition 0.000 description 1
- 240000003291 Armoracia rusticana Species 0.000 description 1
- 235000011330 Armoracia rusticana Nutrition 0.000 description 1
- 102100024630 Asc-type amino acid transporter 1 Human genes 0.000 description 1
- 241000228212 Aspergillus Species 0.000 description 1
- 108090001008 Avidin Proteins 0.000 description 1
- 102000005738 B7 Antigens Human genes 0.000 description 1
- 238000009020 BCA Protein Assay Kit Methods 0.000 description 1
- WOVKYSAHUYNSMH-UHFFFAOYSA-N BROMODEOXYURIDINE Natural products C1C(O)C(CO)OC1N1C(=O)NC(=O)C(Br)=C1 WOVKYSAHUYNSMH-UHFFFAOYSA-N 0.000 description 1
- 241000193830 Bacillus <bacterium> Species 0.000 description 1
- 241000193388 Bacillus thuringiensis Species 0.000 description 1
- 108700003860 Bacterial Genes Proteins 0.000 description 1
- 241000132028 Bellis Species 0.000 description 1
- 102100027314 Beta-2-microglobulin Human genes 0.000 description 1
- 241000283726 Bison Species 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 241000030939 Bubalus bubalis Species 0.000 description 1
- 210000001266 CD8-positive T-lymphocyte Anatomy 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 241000282836 Camelus dromedarius Species 0.000 description 1
- 101100485230 Campylobacter jejuni subsp. jejuni serotype O:2 (strain ATCC 700819 / NCTC 11168) xerH gene Proteins 0.000 description 1
- 108090000565 Capsid Proteins Proteins 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 102000016289 Cell Adhesion Molecules Human genes 0.000 description 1
- 102100023321 Ceruloplasmin Human genes 0.000 description 1
- 102000019034 Chemokines Human genes 0.000 description 1
- 108010012236 Chemokines Proteins 0.000 description 1
- 108091060290 Chromatid Proteins 0.000 description 1
- 241001533384 Circovirus Species 0.000 description 1
- 108020004705 Codon Proteins 0.000 description 1
- 102000029816 Collagenase Human genes 0.000 description 1
- 108060005980 Collagenase Proteins 0.000 description 1
- 108010069112 Complement System Proteins Proteins 0.000 description 1
- 102000000989 Complement System Proteins Human genes 0.000 description 1
- 102100025680 Complement decay-accelerating factor Human genes 0.000 description 1
- 241000711573 Coronaviridae Species 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 230000026774 DNA mediated transformation Effects 0.000 description 1
- 229940021995 DNA vaccine Drugs 0.000 description 1
- 206010011968 Decreased immune responsiveness Diseases 0.000 description 1
- 108090000204 Dipeptidase 1 Proteins 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 239000012591 Dulbecco’s Phosphate Buffered Saline Substances 0.000 description 1
- 238000008157 ELISA kit Methods 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 208000032163 Emerging Communicable disease Diseases 0.000 description 1
- 241000283073 Equus caballus Species 0.000 description 1
- 241000283070 Equus zebra Species 0.000 description 1
- 206010061126 Escherichia infection Diseases 0.000 description 1
- 241000701959 Escherichia virus Lambda Species 0.000 description 1
- 108010022894 Euchromatin Proteins 0.000 description 1
- 206010015548 Euthanasia Diseases 0.000 description 1
- 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 1
- 208000019331 Foodborne disease Diseases 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 101000834253 Gallus gallus Actin, cytoplasmic 1 Proteins 0.000 description 1
- 208000007882 Gastritis Diseases 0.000 description 1
- 241000283899 Gazella Species 0.000 description 1
- 206010064571 Gene mutation Diseases 0.000 description 1
- 241000282816 Giraffa camelopardalis Species 0.000 description 1
- 108010055629 Glucosyltransferases Proteins 0.000 description 1
- 102000000340 Glucosyltransferases Human genes 0.000 description 1
- 102000006771 Gonadotropins Human genes 0.000 description 1
- 108010086677 Gonadotropins Proteins 0.000 description 1
- 208000031886 HIV Infections Diseases 0.000 description 1
- 208000037357 HIV infectious disease Diseases 0.000 description 1
- 102100021519 Hemoglobin subunit beta Human genes 0.000 description 1
- 108091005904 Hemoglobin subunit beta Proteins 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- 241000282821 Hippopotamus Species 0.000 description 1
- 101000856022 Homo sapiens Complement decay-accelerating factor Proteins 0.000 description 1
- 101000740205 Homo sapiens Sal-like protein 1 Proteins 0.000 description 1
- 208000019758 Hypergammaglobulinemia Diseases 0.000 description 1
- 206010020983 Hypogammaglobulinaemia Diseases 0.000 description 1
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 1
- 102100039352 Immunoglobulin heavy constant mu Human genes 0.000 description 1
- 206010062016 Immunosuppression Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 102100034343 Integrase Human genes 0.000 description 1
- 102000012330 Integrases Human genes 0.000 description 1
- 102000004058 Leukemia inhibitory factor Human genes 0.000 description 1
- 108090000581 Leukemia inhibitory factor Proteins 0.000 description 1
- 239000000232 Lipid Bilayer Substances 0.000 description 1
- 241000186781 Listeria Species 0.000 description 1
- 206010024641 Listeriosis Diseases 0.000 description 1
- 208000035752 Live birth Diseases 0.000 description 1
- 230000027311 M phase Effects 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 241001608711 Melo Species 0.000 description 1
- 102000029749 Microtubule Human genes 0.000 description 1
- 108091022875 Microtubule Proteins 0.000 description 1
- 102000003979 Mineralocorticoid Receptors Human genes 0.000 description 1
- 108090000375 Mineralocorticoid Receptors Proteins 0.000 description 1
- 241000711408 Murine respirovirus Species 0.000 description 1
- 101100293737 Mus musculus Nde1 gene Proteins 0.000 description 1
- 229930193140 Neomycin Natural products 0.000 description 1
- 239000000020 Nitrocellulose Substances 0.000 description 1
- 241001263478 Norovirus Species 0.000 description 1
- 238000000636 Northern blotting Methods 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- 241000008357 Okapia johnstoni Species 0.000 description 1
- 241000150452 Orthohantavirus Species 0.000 description 1
- 208000009620 Orthomyxoviridae Infections Diseases 0.000 description 1
- 101710160107 Outer membrane protein A Proteins 0.000 description 1
- 239000012807 PCR reagent Substances 0.000 description 1
- 101150071716 PCSK1 gene Proteins 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 108020002230 Pancreatic Ribonuclease Proteins 0.000 description 1
- 102000005891 Pancreatic ribonuclease Human genes 0.000 description 1
- 101710149632 Pectinesterase A Proteins 0.000 description 1
- 102000003992 Peroxidases Human genes 0.000 description 1
- 241000647372 Promitobates lager Species 0.000 description 1
- 102000009516 Protein Serine-Threonine Kinases Human genes 0.000 description 1
- 108010009341 Protein Serine-Threonine Kinases Proteins 0.000 description 1
- 108010076504 Protein Sorting Signals Proteins 0.000 description 1
- 241000125945 Protoparvovirus Species 0.000 description 1
- 241000589516 Pseudomonas Species 0.000 description 1
- 108020005067 RNA Splice Sites Proteins 0.000 description 1
- 108020005091 Replication Origin Proteins 0.000 description 1
- 206010038997 Retroviral infections Diseases 0.000 description 1
- 241000282806 Rhinoceros Species 0.000 description 1
- 102000006382 Ribonucleases Human genes 0.000 description 1
- 108010083644 Ribonucleases Proteins 0.000 description 1
- 206010067470 Rotavirus infection Diseases 0.000 description 1
- 241000282849 Ruminantia Species 0.000 description 1
- 230000018199 S phase Effects 0.000 description 1
- 241000315672 SARS coronavirus Species 0.000 description 1
- 102100037204 Sal-like protein 1 Human genes 0.000 description 1
- 108020004487 Satellite DNA Proteins 0.000 description 1
- 238000012300 Sequence Analysis Methods 0.000 description 1
- 241000854711 Shinkai Species 0.000 description 1
- 101150081875 Slc7a10 gene Proteins 0.000 description 1
- 102000015215 Stem Cell Factor Human genes 0.000 description 1
- 108010039445 Stem Cell Factor Proteins 0.000 description 1
- 241000264435 Streptococcus dysgalactiae subsp. equisimilis Species 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 230000020385 T cell costimulation Effects 0.000 description 1
- 108091008035 T cell costimulatory receptors Proteins 0.000 description 1
- 230000006052 T cell proliferation Effects 0.000 description 1
- 241000283068 Tapiridae Species 0.000 description 1
- 208000035199 Tetraploidy Diseases 0.000 description 1
- 102000006601 Thymidine Kinase Human genes 0.000 description 1
- 108020004440 Thymidine kinase Proteins 0.000 description 1
- 108010010574 Tn3 resolvase Proteins 0.000 description 1
- 102000004357 Transferases Human genes 0.000 description 1
- 108090000992 Transferases Proteins 0.000 description 1
- 206010052779 Transplant rejections Diseases 0.000 description 1
- 239000007984 Tris EDTA buffer Substances 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 208000034784 Tularaemia Diseases 0.000 description 1
- GUARTUJKFNAVIK-QPTWMBCESA-N Tulathromycin A Chemical compound C1[C@](OC)(C)[C@@](CNCCC)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](C)C(=O)O[C@H](CC)[C@@](C)(O)[C@H](O)[C@@H](C)NC[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C GUARTUJKFNAVIK-QPTWMBCESA-N 0.000 description 1
- 206010053613 Type IV hypersensitivity reaction Diseases 0.000 description 1
- GBOGMAARMMDZGR-UHFFFAOYSA-N UNPD149280 Natural products N1C(=O)C23OC(=O)C=CC(O)CCCC(C)CC=CC3C(O)C(=C)C(C)C2C1CC1=CC=CC=C1 GBOGMAARMMDZGR-UHFFFAOYSA-N 0.000 description 1
- 108010078072 VDJ Recombinases Proteins 0.000 description 1
- 206010058874 Viraemia Diseases 0.000 description 1
- 241000710886 West Nile virus Species 0.000 description 1
- 238000005281 X-ray Gandolfi Methods 0.000 description 1
- 229960003697 abatacept Drugs 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 210000001789 adipocyte Anatomy 0.000 description 1
- 230000001919 adrenal effect Effects 0.000 description 1
- 210000004504 adult stem cell Anatomy 0.000 description 1
- 230000009824 affinity maturation Effects 0.000 description 1
- 239000011543 agarose gel Substances 0.000 description 1
- 230000004520 agglutination Effects 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 229960000548 alemtuzumab Drugs 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 230000007720 allelic exclusion Effects 0.000 description 1
- 235000020224 almond Nutrition 0.000 description 1
- 238000000137 annealing Methods 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 230000005875 antibody response Effects 0.000 description 1
- 230000007503 antigenic stimulation Effects 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 210000000709 aorta Anatomy 0.000 description 1
- 210000002403 aortic endothelial cell Anatomy 0.000 description 1
- 210000003433 aortic smooth muscle cell Anatomy 0.000 description 1
- 238000003782 apoptosis assay Methods 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 210000001130 astrocyte Anatomy 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 230000002238 attenuated effect Effects 0.000 description 1
- 229940097012 bacillus thuringiensis Drugs 0.000 description 1
- 230000007924 bacterial virulence factor Effects 0.000 description 1
- 229910052788 barium Inorganic materials 0.000 description 1
- DSAJWYNOEDNPEQ-UHFFFAOYSA-N barium atom Chemical compound [Ba] DSAJWYNOEDNPEQ-UHFFFAOYSA-N 0.000 description 1
- 210000003651 basophil Anatomy 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 108010081355 beta 2-Microglobulin Proteins 0.000 description 1
- 102000006635 beta-lactamase Human genes 0.000 description 1
- 239000003124 biologic agent Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 238000010170 biological method Methods 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- OWMVSZAMULFTJU-UHFFFAOYSA-N bis-tris Chemical compound OCCN(CCO)C(CO)(CO)CO OWMVSZAMULFTJU-UHFFFAOYSA-N 0.000 description 1
- 210000003443 bladder cell Anatomy 0.000 description 1
- 238000004820 blood count Methods 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 210000002449 bone cell Anatomy 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 229950004398 broxuridine Drugs 0.000 description 1
- 239000008366 buffered solution Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 244000309466 calf Species 0.000 description 1
- 229940112129 campath Drugs 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 102000008395 cell adhesion mediator activity proteins Human genes 0.000 description 1
- 230000022131 cell cycle Effects 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 230000007910 cell fusion Effects 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 238000001516 cell proliferation assay Methods 0.000 description 1
- 230000005101 cell tropism Effects 0.000 description 1
- 230000007969 cellular immunity Effects 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 239000013043 chemical agent Substances 0.000 description 1
- 229940044683 chemotherapy drug Drugs 0.000 description 1
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
- 210000004756 chromatid Anatomy 0.000 description 1
- 210000000254 ciliated cell Anatomy 0.000 description 1
- 108010087471 cin recombinase Proteins 0.000 description 1
- 101150076615 ck gene Proteins 0.000 description 1
- 239000000701 coagulant Substances 0.000 description 1
- 229960002424 collagenase Drugs 0.000 description 1
- 238000004891 communication Methods 0.000 description 1
- 230000024203 complement activation Effects 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 230000030944 contact inhibition Effects 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000009260 cross reactivity Effects 0.000 description 1
- 238000005138 cryopreservation Methods 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- GBOGMAARMMDZGR-JREHFAHYSA-N cytochalasin B Natural products C[C@H]1CCC[C@@H](O)C=CC(=O)O[C@@]23[C@H](C=CC1)[C@H](O)C(=C)[C@@H](C)[C@@H]2[C@H](Cc4ccccc4)NC3=O GBOGMAARMMDZGR-JREHFAHYSA-N 0.000 description 1
- GBOGMAARMMDZGR-TYHYBEHESA-N cytochalasin B Chemical compound C([C@H]1[C@@H]2[C@@H](C([C@@H](O)[C@@H]3/C=C/C[C@H](C)CCC[C@@H](O)/C=C/C(=O)O[C@@]23C(=O)N1)=C)C)C1=CC=CC=C1 GBOGMAARMMDZGR-TYHYBEHESA-N 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 238000002784 cytotoxicity assay Methods 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 210000004443 dendritic cell Anatomy 0.000 description 1
- 230000000368 destabilizing effect Effects 0.000 description 1
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
- 229960003957 dexamethasone Drugs 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 230000001079 digestive effect Effects 0.000 description 1
- 208000010643 digestive system disease Diseases 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 238000006471 dimerization reaction Methods 0.000 description 1
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 229940119542 draxxin Drugs 0.000 description 1
- 241001493065 dsRNA viruses Species 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 230000000464 effect on transcription Effects 0.000 description 1
- 230000005611 electricity Effects 0.000 description 1
- 210000002308 embryonic cell Anatomy 0.000 description 1
- 210000005168 endometrial cell Anatomy 0.000 description 1
- 210000002472 endoplasmic reticulum Anatomy 0.000 description 1
- HKSZLNNOFSGOKW-UHFFFAOYSA-N ent-staurosporine Natural products C12=C3N4C5=CC=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1C1CC(NC)C(OC)C4(C)O1 HKSZLNNOFSGOKW-UHFFFAOYSA-N 0.000 description 1
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 1
- 210000003979 eosinophil Anatomy 0.000 description 1
- 210000003386 epithelial cell of thymus gland Anatomy 0.000 description 1
- 208000020612 escherichia coli infection Diseases 0.000 description 1
- 239000003797 essential amino acid Substances 0.000 description 1
- 235000020776 essential amino acid Nutrition 0.000 description 1
- 235000020774 essential nutrients Nutrition 0.000 description 1
- 210000000632 euchromatin Anatomy 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 230000008218 female gametogenesis Effects 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 101150042777 flp gene Proteins 0.000 description 1
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 1
- 210000004186 follicle cell Anatomy 0.000 description 1
- 230000037433 frameshift Effects 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 230000000799 fusogenic effect Effects 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 238000003209 gene knockout Methods 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 210000002175 goblet cell Anatomy 0.000 description 1
- 239000002622 gonadotropin Substances 0.000 description 1
- 230000036449 good health Effects 0.000 description 1
- 239000011544 gradient gel Substances 0.000 description 1
- 210000002503 granulosa cell Anatomy 0.000 description 1
- 239000005090 green fluorescent protein Substances 0.000 description 1
- 210000002768 hair cell Anatomy 0.000 description 1
- 210000004919 hair shaft Anatomy 0.000 description 1
- 230000012447 hatching Effects 0.000 description 1
- 210000002064 heart cell Anatomy 0.000 description 1
- 210000005003 heart tissue Anatomy 0.000 description 1
- 230000002489 hematologic effect Effects 0.000 description 1
- 238000007490 hematoxylin and eosin (H&E) staining Methods 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 210000003494 hepatocyte Anatomy 0.000 description 1
- 238000000265 homogenisation Methods 0.000 description 1
- 102000044446 human CD46 Human genes 0.000 description 1
- 102000051442 human CD59 Human genes 0.000 description 1
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 230000008938 immune dysregulation Effects 0.000 description 1
- 230000008105 immune reaction Effects 0.000 description 1
- 230000003053 immunization Effects 0.000 description 1
- 238000002649 immunization Methods 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 238000003365 immunocytochemistry Methods 0.000 description 1
- 238000011563 immunodeficient animal model Methods 0.000 description 1
- 238000011575 immunodeficient mouse model Methods 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 238000011532 immunohistochemical staining Methods 0.000 description 1
- 230000002134 immunopathologic effect Effects 0.000 description 1
- 230000001506 immunosuppresive effect Effects 0.000 description 1
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 229940125721 immunosuppressive agent Drugs 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000000415 inactivating effect Effects 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000036512 infertility Effects 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000009027 insemination Effects 0.000 description 1
- 230000031891 intestinal absorption Effects 0.000 description 1
- 208000028774 intestinal disease Diseases 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 230000005865 ionizing radiation Effects 0.000 description 1
- 239000002555 ionophore Substances 0.000 description 1
- 230000000236 ionophoric effect Effects 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- BPHPUYQFMNQIOC-NXRLNHOXSA-N isopropyl beta-D-thiogalactopyranoside Chemical compound CC(C)S[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O BPHPUYQFMNQIOC-NXRLNHOXSA-N 0.000 description 1
- 230000003780 keratinization Effects 0.000 description 1
- 210000003292 kidney cell Anatomy 0.000 description 1
- 210000002415 kinetochore Anatomy 0.000 description 1
- 238000011813 knockout mouse model Methods 0.000 description 1
- 210000001865 kupffer cell Anatomy 0.000 description 1
- 238000011005 laboratory method Methods 0.000 description 1
- 208000021601 lentivirus infection Diseases 0.000 description 1
- 210000002332 leydig cell Anatomy 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 210000005228 liver tissue Anatomy 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 210000005265 lung cell Anatomy 0.000 description 1
- 230000002934 lysing effect Effects 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 238000002826 magnetic-activated cell sorting Methods 0.000 description 1
- 210000000415 mammalian chromosome Anatomy 0.000 description 1
- 210000004216 mammary stem cell Anatomy 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000013011 mating Effects 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 235000019988 mead Nutrition 0.000 description 1
- 230000021121 meiosis Effects 0.000 description 1
- 230000037353 metabolic pathway Effects 0.000 description 1
- 230000037323 metabolic rate Effects 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 210000004688 microtubule Anatomy 0.000 description 1
- 210000004925 microvascular endothelial cell Anatomy 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 210000003550 mucous cell Anatomy 0.000 description 1
- 229940031348 multivalent vaccine Drugs 0.000 description 1
- 210000004457 myocytus nodalis Anatomy 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 210000004498 neuroglial cell Anatomy 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 229920001220 nitrocellulos Polymers 0.000 description 1
- 238000010449 nuclear transplantation Methods 0.000 description 1
- 229940060568 nuflor Drugs 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 244000039328 opportunistic pathogen Species 0.000 description 1
- 210000000963 osteoblast Anatomy 0.000 description 1
- 210000002997 osteoclast Anatomy 0.000 description 1
- 210000004409 osteocyte Anatomy 0.000 description 1
- 230000002611 ovarian Effects 0.000 description 1
- 210000004923 pancreatic tissue Anatomy 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 230000003071 parasitic effect Effects 0.000 description 1
- 230000000849 parathyroid Effects 0.000 description 1
- 230000032696 parturition Effects 0.000 description 1
- 230000007918 pathogenicity Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 230000007908 penetration of oocytes Effects 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- 229940066827 pertussis vaccine Drugs 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 238000000053 physical method Methods 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 230000001817 pituitary effect Effects 0.000 description 1
- 210000004180 plasmocyte Anatomy 0.000 description 1
- 230000008488 polyadenylation Effects 0.000 description 1
- 102000040430 polynucleotide Human genes 0.000 description 1
- 108091033319 polynucleotide Proteins 0.000 description 1
- 239000002157 polynucleotide Substances 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 230000009290 primary effect Effects 0.000 description 1
- 208000028529 primary immunodeficiency disease Diseases 0.000 description 1
- 210000001948 pro-b lymphocyte Anatomy 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000031877 prophase Effects 0.000 description 1
- 229940043274 prophylactic drug Drugs 0.000 description 1
- 210000005267 prostate cell Anatomy 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 229950010131 puromycin Drugs 0.000 description 1
- 229940076788 pyruvate Drugs 0.000 description 1
- 230000000384 rearing effect Effects 0.000 description 1
- 210000003289 regulatory T cell Anatomy 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000009711 regulatory function Effects 0.000 description 1
- 210000005084 renal tissue Anatomy 0.000 description 1
- 238000009256 replacement therapy Methods 0.000 description 1
- 210000005000 reproductive tract Anatomy 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 208000023504 respiratory system disease Diseases 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 230000002207 retinal effect Effects 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 238000003118 sandwich ELISA Methods 0.000 description 1
- 235000013580 sausages Nutrition 0.000 description 1
- 210000004116 schwann cell Anatomy 0.000 description 1
- 230000009291 secondary effect Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 238000005204 segregation Methods 0.000 description 1
- 239000006152 selective media Substances 0.000 description 1
- 230000009758 senescence Effects 0.000 description 1
- 230000000405 serological effect Effects 0.000 description 1
- 210000000717 sertoli cell Anatomy 0.000 description 1
- 230000007781 signaling event Effects 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 1
- CBHOWTTXCQAOID-UHFFFAOYSA-L sodium ethane formaldehyde mercury(2+) molecular iodine 2-sulfidobenzoate Chemical class [Na+].[Hg++].C[CH2-].II.C=O.[O-]C(=O)c1ccccc1[S-] CBHOWTTXCQAOID-UHFFFAOYSA-L 0.000 description 1
- 229940054269 sodium pyruvate Drugs 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- WWUZIQQURGPMPG-KRWOKUGFSA-N sphingosine Chemical compound CCCCCCCCCCCCC\C=C\[C@@H](O)[C@@H](N)CO WWUZIQQURGPMPG-KRWOKUGFSA-N 0.000 description 1
- 210000004989 spleen cell Anatomy 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 210000004085 squamous epithelial cell Anatomy 0.000 description 1
- HKSZLNNOFSGOKW-FYTWVXJKSA-N staurosporine Chemical compound C12=C3N4C5=CC=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1[C@H]1C[C@@H](NC)[C@@H](OC)[C@]4(C)O1 HKSZLNNOFSGOKW-FYTWVXJKSA-N 0.000 description 1
- CGPUWJWCVCFERF-UHFFFAOYSA-N staurosporine Natural products C12=C3N4C5=CC=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1C1CC(NC)C(OC)C4(OC)O1 CGPUWJWCVCFERF-UHFFFAOYSA-N 0.000 description 1
- 210000004500 stellate cell Anatomy 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 230000035882 stress Effects 0.000 description 1
- 210000002536 stromal cell Anatomy 0.000 description 1
- 229910052712 strontium Inorganic materials 0.000 description 1
- CIOAGBVUUVVLOB-UHFFFAOYSA-N strontium atom Chemical compound [Sr] CIOAGBVUUVVLOB-UHFFFAOYSA-N 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 238000011477 surgical intervention Methods 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000009392 systemic autoimmunity Effects 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 210000004876 tela submucosa Anatomy 0.000 description 1
- 208000001608 teratocarcinoma Diseases 0.000 description 1
- 230000002381 testicular Effects 0.000 description 1
- 230000002992 thymic effect Effects 0.000 description 1
- 229940107955 thymoglobulin Drugs 0.000 description 1
- 210000001541 thymus gland Anatomy 0.000 description 1
- 210000001685 thyroid gland Anatomy 0.000 description 1
- 230000005100 tissue tropism Effects 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 230000010415 tropism Effects 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- 210000003606 umbilical vein Anatomy 0.000 description 1
- 241000712461 unidentified influenza virus Species 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 239000013603 viral vector Substances 0.000 description 1
- 210000001835 viscera Anatomy 0.000 description 1
- 238000012800 visualization Methods 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 101150060755 xerC gene Proteins 0.000 description 1
- 101150005813 xerD gene Proteins 0.000 description 1
- 210000004340 zona pellucida Anatomy 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K67/00—Rearing or breeding animals, not otherwise provided for; New or modified breeds of animals
- A01K67/027—New or modified breeds of vertebrates
- A01K67/0275—Genetically modified vertebrates, e.g. transgenic
- A01K67/0276—Knock-out vertebrates
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K67/00—Rearing or breeding animals, not otherwise provided for; New or modified breeds of animals
- A01K67/027—New or modified breeds of vertebrates
- A01K67/0273—Cloned vertebrates
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K67/00—Rearing or breeding animals, not otherwise provided for; New or modified breeds of animals
- A01K67/027—New or modified breeds of vertebrates
- A01K67/0275—Genetically modified vertebrates, e.g. transgenic
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70503—Immunoglobulin superfamily
- C07K14/70521—CD28, CD152
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
- C12N15/8509—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells for producing genetically modified animals, e.g. transgenic
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
- G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
- G01N33/5082—Supracellular entities, e.g. tissue, organisms
- G01N33/5088—Supracellular entities, e.g. tissue, organisms of vertebrates
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2217/00—Genetically modified animals
- A01K2217/05—Animals comprising random inserted nucleic acids (transgenic)
- A01K2217/052—Animals comprising random inserted nucleic acids (transgenic) inducing gain of function
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2217/00—Genetically modified animals
- A01K2217/07—Animals genetically altered by homologous recombination
- A01K2217/075—Animals genetically altered by homologous recombination inducing loss of function, i.e. knock out
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2227/00—Animals characterised by species
- A01K2227/10—Mammal
- A01K2227/108—Swine
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2267/00—Animals characterised by purpose
- A01K2267/01—Animal expressing industrially exogenous proteins
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2267/00—Animals characterised by purpose
- A01K2267/03—Animal model, e.g. for test or diseases
- A01K2267/035—Animal model for multifactorial diseases
- A01K2267/0387—Animal model for diseases of the immune system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/30—Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
- C12N15/8509—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells for producing genetically modified animals, e.g. transgenic
- C12N2015/8518—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells for producing genetically modified animals, e.g. transgenic expressing industrially exogenous proteins, e.g. for pharmaceutical use, human insulin, blood factors, immunoglobulins, pseudoparticles
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
- C12N15/8509—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells for producing genetically modified animals, e.g. transgenic
- C12N2015/8527—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells for producing genetically modified animals, e.g. transgenic for producing animal models, e.g. for tests or diseases
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Zoology (AREA)
- Biomedical Technology (AREA)
- General Health & Medical Sciences (AREA)
- Environmental Sciences (AREA)
- Genetics & Genomics (AREA)
- Biotechnology (AREA)
- Immunology (AREA)
- Veterinary Medicine (AREA)
- Organic Chemistry (AREA)
- Molecular Biology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biochemistry (AREA)
- Biodiversity & Conservation Biology (AREA)
- Animal Husbandry (AREA)
- Animal Behavior & Ethology (AREA)
- Cell Biology (AREA)
- General Engineering & Computer Science (AREA)
- Wood Science & Technology (AREA)
- Biophysics (AREA)
- Microbiology (AREA)
- Physics & Mathematics (AREA)
- Urology & Nephrology (AREA)
- Hematology (AREA)
- Medicinal Chemistry (AREA)
- Toxicology (AREA)
- Plant Pathology (AREA)
- Gastroenterology & Hepatology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Food Science & Technology (AREA)
- Analytical Chemistry (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Claims (16)
1. Fremgangsmåde til at teste immunresponset på et dyr til et antigen omfattende tilvejebringelse af et genetisk modificeret svin der mangler ekspression af funktionelt tung kæde immunoglobulin fra svin med antigenet og bedømmelse af et respons fra dyret til antigenet, hvor svinet har en targeteret disruption i begge alleiler af den J6-samlende region af den tunge kæde fra svin, der resulterer i en mangel af B-celleproduktion i svinet.
2. Fremgangsmåden ifølge krav 1, hvor svinet har en disruption i mindst ét yderligere nativt gen i dets genom.
3. Fremgangsmåden ifølge krav 2, hvor svinet mangler eller har reduceret cellulært immunrespons.
4. Fremgangsmåden ifølge krav 1 eller krav 3, hvor svinet yderligere omfatter mindst ét xenogent gen eller transgen.
5. Fremgangsmåden ifølge krav 4, hvor svinet yderligere udtrykket mindst ét xenogent protein.
6. Fremgangsmåden ifølge krav 5, hvor det yderligere protein er et kostimulatorisk blokeringsmolekyle.
7. Fremgangsmåden ifølge krav 6, hvor det kostimulatoriske blokeringsmolekyle er cytotoksisk T-lymfocyt associeret protein 4 (CTLA4).
8. Fremgangsmåden ifølge krav 7, hvor CTLA4 er fusioneret til et immunoglobulin (Ig)-molekyle.
9. Fremgangsmåde til at teste anvendeligheden af et profylaktisk eller terapeutisk middel mod et infektiøst middel omfattende eksponering af et genetisk modificeret svin der mangler ekspression af funktionelt tung kæde immunoglobulin fra svin med det infektiøse middel; behandle svinet med profylaktisk eller terapeutisk middel; og bedømme immunresponset og infektionsforløbet i svinet; hvor svinet har en targeteret gennemslag i begge allelier af den J6-samlende region af den tunge kæde fra svin , der resulterer i en mangel af B-celleproduktion i svinet.
10. Fremgangsmåden ifølge krav 1 eller krav 9, hvor svinet angribes med et infektiøst middel eller overfladeantigen deraf.
11. Fremgangsmåden ifølge krav 9 eller krav 10, hvor bedømmelsen omfatter undersøgelse af cellulære og humorale responser.
12. Fremgangsmåden ifølge krav 10, hvor det infektiøse middel er et virus.
13. Fremgangsmåden ifølge krav 9, hvor det profylaktiske eller terapeutiske middel er en vaccine.
14. Fremgangsmåden ifølge et hvilket som helst af kravene 9-13, hvor dyret yderligere udtrykker et exogent protein.
15. Fremgangsmåden ifølge krav 14, hvor det yderligere protein er et humant immunoglobulin eller fragment deraf.
16. Fremgangsmåden ifølge et hvilket som helst af de foregående krav, hvor svinet har en targeteret deletion af den J6-samlende region af det tunge kæde fra svine Ig-gen.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US10874208P | 2008-10-27 | 2008-10-27 | |
| PCT/US2009/062265 WO2010051288A1 (en) | 2008-10-27 | 2009-10-27 | Immunocompromised ungulates |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DK2348827T3 true DK2348827T3 (da) | 2015-07-20 |
Family
ID=42129233
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK09824080.7T DK2348827T3 (da) | 2008-10-27 | 2009-10-27 | Immunkompromitterede hovdyr |
Country Status (5)
| Country | Link |
|---|---|
| US (2) | US20120090039A1 (da) |
| EP (1) | EP2348827B1 (da) |
| DK (1) | DK2348827T3 (da) |
| ES (1) | ES2548377T3 (da) |
| WO (1) | WO2010051288A1 (da) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2585098C (en) * | 2004-10-22 | 2018-12-18 | Revivicor, Inc. | Porcine genomic kappa and lambda light chain sequences |
| KR20180036810A (ko) * | 2009-08-14 | 2018-04-09 | 레비비코르 인코포레이션 | 당뇨병 치료를 위한 복수 형질전환 돼지 |
| CN116732106A (zh) | 2017-04-20 | 2023-09-12 | E开创生物技术股份有限公司 | 产生基因修改的动物的方法 |
| US10883084B2 (en) | 2018-10-05 | 2021-01-05 | Xenotherapeutics, Inc. | Personalized cells, tissues, and organs for transplantation from a humanized, bespoke, designated-pathogen free, (non-human) donor and methods and products relating to same |
| MX2021003866A (es) | 2018-10-05 | 2021-09-08 | Xenotherapeutics Inc | Productos y metodos de xenotransplante. |
| IL302830A (en) | 2020-11-13 | 2023-07-01 | Egenesis Inc | Cells, tissues, organs and animals with one or more genes that have been modified for improved survival and tolerance of a different-sex transplant |
Family Cites Families (210)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4873191A (en) | 1981-06-12 | 1989-10-10 | Ohio University | Genetic transformation of zygotes |
| US4994384A (en) | 1986-12-31 | 1991-02-19 | W. R. Grace & Co.-Conn. | Multiplying bovine embryos |
| US4889806A (en) | 1987-04-15 | 1989-12-26 | Washington University | Large DNA cloning system based on yeast artificial chromosomes |
| US5057420A (en) | 1987-06-05 | 1991-10-15 | Granada Biosciences, Inc. | Bovine nuclear transplantation |
| JPH03503599A (ja) | 1988-03-24 | 1991-08-15 | ザ・ジェネラル・ホスピタル・コーポレーション | 人工染色体ベクター |
| US5270201A (en) | 1988-03-24 | 1993-12-14 | The General Hospital Corporation | Artificial chromosome vector |
| EP0435928A1 (en) | 1988-09-21 | 1991-07-10 | Animal Biotechnology Cambridge Limited | Derivation of pluripotential embryonic cell lines from domestic animals |
| GB8823869D0 (en) | 1988-10-12 | 1988-11-16 | Medical Res Council | Production of antibodies |
| US5175384A (en) | 1988-12-05 | 1992-12-29 | Genpharm International | Transgenic mice depleted in mature t-cells and methods for making transgenic mice |
| US4944384A (en) | 1989-01-30 | 1990-07-31 | Hay & Forage Industries | Trash discharge apparatus for crop transferring conveyor mechanism |
| US4997384A (en) | 1989-04-17 | 1991-03-05 | Otis Engineering Corporation | Wet connector |
| GB8920211D0 (en) | 1989-09-07 | 1989-10-18 | Ici Plc | Diagnostic method |
| SG88714A1 (en) | 1989-11-06 | 2002-05-21 | Cell Genesys Inc | Production of proteins using homologous recombination |
| EP1690935A3 (en) | 1990-01-12 | 2008-07-30 | Abgenix, Inc. | Generation of xenogeneic antibodies |
| EP0539490B1 (en) | 1990-07-13 | 1995-11-08 | Transkaryotic Therapies, Inc. | Library screening method |
| US5770429A (en) | 1990-08-29 | 1998-06-23 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| US5633425A (en) | 1990-08-29 | 1997-05-27 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| US5625126A (en) | 1990-08-29 | 1997-04-29 | Genpharm International, Inc. | Transgenic non-human animals for producing heterologous antibodies |
| US5661016A (en) | 1990-08-29 | 1997-08-26 | Genpharm International Inc. | Transgenic non-human animals capable of producing heterologous antibodies of various isotypes |
| US5814318A (en) | 1990-08-29 | 1998-09-29 | Genpharm International Inc. | Transgenic non-human animals for producing heterologous antibodies |
| US5545806A (en) | 1990-08-29 | 1996-08-13 | Genpharm International, Inc. | Ransgenic non-human animals for producing heterologous antibodies |
| US5789650A (en) | 1990-08-29 | 1998-08-04 | Genpharm International, Inc. | Transgenic non-human animals for producing heterologous antibodies |
| CA2090473A1 (en) | 1990-08-29 | 1992-03-01 | Robert M. Kay | Homologous recombinatin in mammalian cells |
| ES2246502T3 (es) | 1990-08-29 | 2006-02-16 | Genpharm International, Inc. | Animales no humanos transgenicos capaces de producir anticuerpos heterologos. |
| US6300129B1 (en) | 1990-08-29 | 2001-10-09 | Genpharm International | Transgenic non-human animals for producing heterologous antibodies |
| WO1992022670A1 (en) | 1991-06-12 | 1992-12-23 | Genpharm International, Inc. | Early detection of transgenic embryos |
| AU2235992A (en) | 1991-06-14 | 1993-01-12 | Genpharm International, Inc. | Transgenic immunodeficient non-human animals |
| WO1993004169A1 (en) | 1991-08-20 | 1993-03-04 | Genpharm International, Inc. | Gene targeting in animal cells using isogenic dna constructs |
| US5288625A (en) | 1991-09-13 | 1994-02-22 | Biologic Research Center Of The Hungarian Academy Of Sciences | Mammalian artificial chromosomes |
| JPH07503132A (ja) | 1991-12-17 | 1995-04-06 | ジェンファーム インターナショナル,インコーポレイティド | 異種抗体を産生することができるトランスジェニック非ヒト動物 |
| US5859307A (en) | 1992-02-04 | 1999-01-12 | Massachusetts Institute Of Technology | Mutant RAG-1 deficient animals having no mature B and T lymphocytes |
| WO1994000569A1 (en) | 1992-06-18 | 1994-01-06 | Genpharm International, Inc. | Methods for producing transgenic non-human animals harboring a yeast artificial chromosome |
| ES2301158T3 (es) | 1992-07-24 | 2008-06-16 | Amgen Fremont Inc. | Produccion de anticuerpos xenogenicos. |
| US5981175A (en) | 1993-01-07 | 1999-11-09 | Genpharm Internation, Inc. | Methods for producing recombinant mammalian cells harboring a yeast artificial chromosome |
| US5496720A (en) | 1993-02-10 | 1996-03-05 | Susko-Parrish; Joan L. | Parthenogenic oocyte activation |
| WO1994023049A2 (en) | 1993-04-02 | 1994-10-13 | The Johns Hopkins University | The introduction and expression of large genomic sequences in transgenic animals |
| GB9308271D0 (en) | 1993-04-21 | 1993-06-02 | Univ Edinburgh | Method of isolating and/or enriching and/or selectively propagating pluripotential animal cells and animals for use in said method |
| AU6819494A (en) | 1993-04-26 | 1994-11-21 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| US6096878A (en) | 1993-05-10 | 2000-08-01 | Japan Tobacco Inc. | Human immunoglobulin VH gene segments and DNA fragments containing the same |
| US5523226A (en) | 1993-05-14 | 1996-06-04 | Biotechnology Research And Development Corp. | Transgenic swine compositions and methods |
| US5851760A (en) | 1993-06-15 | 1998-12-22 | The Salk Institute For Biological Studies | Method for generation of sequence sampled maps of complex genomes |
| WO1995003400A1 (en) | 1993-07-23 | 1995-02-02 | Johns Hopkins University School Of Medicine | Recombinationally targeted cloning in yeast artificial chromosomes |
| EP0804222A4 (en) | 1993-08-20 | 1998-08-12 | Univ New Jersey Med | ADDITIONAL FACTOR FUNCTION FOR INTERFERONGAMMA AND THEIR RECEPTOR |
| US5597694A (en) | 1993-10-07 | 1997-01-28 | Massachusetts Institute Of Technology | Interspersed repetitive element-bubble amplification of nucleic acids |
| US5625825A (en) | 1993-10-21 | 1997-04-29 | Lsi Logic Corporation | Random number generating apparatus for an interface unit of a carrier sense with multiple access and collision detect (CSMA/CD) ethernet data network |
| JPH09509046A (ja) | 1993-11-29 | 1997-09-16 | ユニヴァーシティ オブ サウス フロリダ | トランスジェニックマウス |
| WO1996001276A1 (en) | 1994-07-06 | 1996-01-18 | University Of Medicine & Dentistry Of New Jersey | Expression of a functional human type i interferon receptor |
| US5643763A (en) | 1994-11-04 | 1997-07-01 | Genpharm International, Inc. | Method for making recombinant yeast artificial chromosomes by minimizing diploid doubling during mating |
| US5733744A (en) | 1995-01-13 | 1998-03-31 | Cornell Research Foundation, Inc. | Binary BAC vector |
| WO1996034096A1 (en) | 1995-04-28 | 1996-10-31 | Abgenix, Inc. | Human antibodies derived from immunized xenomice |
| US5877159A (en) | 1995-05-03 | 1999-03-02 | University Of Maryland At Baltimore | Method for introducing and expressing genes in animal cells and live invasive bacterial vectors for use in the same |
| US6150170A (en) | 1998-05-03 | 2000-11-21 | University Of Maryland At Baltimore | Method for introducing and expressing genes in animal cells, and live invasive bacterial vectors for use in the same |
| US6682729B1 (en) | 1995-05-03 | 2004-01-27 | University Of Maryland, Baltimore | Method for introducing and expressing genes in animal cells, and live invasive bacterial vectors for use in the same |
| US6348353B1 (en) | 1995-06-07 | 2002-02-19 | Case Western Reserve University | Artificial mammalian chromosome |
| US5985846A (en) | 1995-06-07 | 1999-11-16 | Baylor College Of Medicine | Gene therapy for muscular dystrophy |
| US6153740A (en) | 1995-07-07 | 2000-11-28 | University Of Alberta | cDNA encoding nucleoside transporter |
| US6455254B1 (en) | 1995-07-18 | 2002-09-24 | Diversa Corporation | Sequence based screening |
| WO1997003999A1 (en) | 1995-07-18 | 1997-02-06 | Washington University School Of Medicine | Mutant s182 genes |
| EP0842283A1 (en) | 1995-07-21 | 1998-05-20 | THE UNITED STATES GOVERNMENT as represented by THE DEPARTMENT OF HEALTH AND HUMAN SERVICES | RecA-ASSISTED CLONING OF DNA |
| EP0773288A3 (en) | 1995-08-29 | 1997-07-09 | Kirin Brewery | Chimera animal and its method of manufacture |
| US6166288A (en) | 1995-09-27 | 2000-12-26 | Nextran Inc. | Method of producing transgenic animals for xenotransplantation expressing both an enzyme masking or reducing the level of the gal epitope and a complement inhibitor |
| US6133503A (en) | 1995-10-31 | 2000-10-17 | The Regents Of The University Of California | Mammalian artificial chromosomes and methods of using same |
| US5721118A (en) | 1995-10-31 | 1998-02-24 | The Regents Of The University Of California, San Diego | Mammalian artificial chromosomes and methods of using same |
| US6150160A (en) | 1995-11-16 | 2000-11-21 | The John Hopkins University | Compositions and methods of use of mammalian retrotransposons |
| US5997881A (en) | 1995-11-22 | 1999-12-07 | University Of Maryland, Baltimore | Method of making non-pyrogenic lipopolysaccharide or A |
| US5866404A (en) | 1995-12-06 | 1999-02-02 | Yale University | Yeast-bacteria shuttle vector |
| US5830696A (en) | 1996-12-05 | 1998-11-03 | Diversa Corporation | Directed evolution of thermophilic enzymes |
| US20020132295A1 (en) | 1996-02-09 | 2002-09-19 | Short Jay M. | Enzymes having transaminase and aminotransferase activity and methods of use thereof |
| US7288400B2 (en) | 1996-02-16 | 2007-10-30 | Verenium Corporation | Nucleic acids encoding esterases and methods of making and using them |
| US6987016B2 (en) | 1996-03-08 | 2006-01-17 | Diversa Corporation | α-galactosidases and methods for making and using them |
| CA2249206A1 (en) | 1996-04-01 | 1997-10-09 | Genentech, Inc. | Apo-2li and apo-3 apoptosis polypeptides |
| US6077697A (en) | 1996-04-10 | 2000-06-20 | Chromos Molecular Systems, Inc. | Artificial chromosomes, uses thereof and methods for preparing artificial chromosomes |
| US6025155A (en) | 1996-04-10 | 2000-02-15 | Chromos Molecular Systems, Inc. | Artificial chromosomes, uses thereof and methods for preparing artificial chromosomes |
| US6495318B2 (en) | 1996-06-17 | 2002-12-17 | Vectorobjects, Llc | Method and kits for preparing multicomponent nucleic acid constructs |
| US20020137185A1 (en) | 1996-06-17 | 2002-09-26 | Jay Short | Enzymes having amidase activity and methods of use thereof |
| EP0814156B1 (en) | 1996-06-18 | 2003-03-05 | The Institute Of Physical & Chemical Research | Method for the purification of DNA |
| US20020102680A1 (en) | 1996-07-03 | 2002-08-01 | Robertson Dan E. | Catalases |
| WO1998001573A1 (en) | 1996-07-09 | 1998-01-15 | The Government Of The United States Of America Represented By The Secretary, Department Of Health And Human Services | Transformation-associated recombination cloning |
| BR9711204A (pt) | 1996-08-19 | 1999-08-17 | Univ Massachusetts | Linhagens de c-lulas embriÄnicas ou similares s indiferenciadas produzidas por transplante nuclear de esp-cies hibridas |
| US6017755A (en) | 1996-08-22 | 2000-01-25 | Hsc Research & Development Limited | MADR2 tumour suppressor gene |
| EP2060633A1 (en) | 1996-08-26 | 2009-05-20 | Chromo Research, Inc. | Mammalian artificial chromosomes |
| US6187533B1 (en) | 1996-09-10 | 2001-02-13 | Arch Development Corporation | Mutations in the diabetes susceptibility genes hepatocyte nuclear factor (HNF) 1 alpha (α), HNF1β and HNF4α |
| EP0927262A1 (de) | 1996-09-18 | 1999-07-07 | Christian Jung | Nematodenresistenzgen |
| AU4318797A (en) | 1996-09-18 | 1998-04-14 | Dnavec Research Inc. | Artificial chromosome |
| US6462176B1 (en) | 1996-09-23 | 2002-10-08 | Genentech, Inc. | Apo-3 polypeptide |
| US6020142A (en) | 1996-10-04 | 2000-02-01 | Millennium Pharmaceuticals, Inc. | Rath genes and polypeptides and methods for the treatment and diagnosis of immune disorders |
| US6287854B1 (en) | 1996-10-22 | 2001-09-11 | Imperial Cancer Research Technology Limited | Diagnosis of susceptibility to cancer and treatment thereof |
| EP1972194A1 (en) | 1996-12-03 | 2008-09-24 | Amgen Fremont Inc. | Transgenic mammals having human ig loci including plural vh and vk regions and antibodies produced therefrom |
| US7279316B2 (en) | 1996-12-06 | 2007-10-09 | Verenium Corporation | Enzymes having glycosidase activity and methods of use thereof |
| US6358523B1 (en) | 1996-12-06 | 2002-03-19 | The Regents Of The University Of California | Macromolecule-lipid complexes and methods for making and regulating |
| EP0948635A2 (en) | 1996-12-16 | 1999-10-13 | McGILL UNIVERSITY | Human and mammalian dna replication origin consensus sequences |
| GB9702802D0 (en) | 1997-02-12 | 1997-04-02 | Babraham The Inst | Yeast artificial chromosomes |
| DK0973928T3 (da) | 1997-03-11 | 2010-08-09 | Univ Minnesota | DNA-baseret transposonsystem til indføring af nukleinsyre i DNA i en celle |
| JP3151657B2 (ja) | 1997-03-26 | 2001-04-03 | 農林水産省農業生物資源研究所長 | 遺伝子導入法 |
| US5843671A (en) | 1997-04-01 | 1998-12-01 | Princeton University | Methods for measuring trinucleotide repeat expansion in Saccharomyces cerevisiae |
| AU741630B2 (en) | 1997-05-07 | 2001-12-06 | Genomics One Corporation | Improved cloning vector containing marker inactivation system |
| EP0996719A4 (en) | 1997-05-13 | 2002-05-08 | Amrad Operations Pty Ltd | A novel nucleic acid molecule |
| US5972649A (en) | 1997-05-29 | 1999-10-26 | Incyte Pharmaceuticals, Inc. | Polynucleotide sequence encoding human multiple endocrine neoplasia type 1 protein |
| AU746775B2 (en) | 1997-06-03 | 2002-05-02 | University Of Chicago, The | Plant artificial chromosome (PLAC) compositions and methods |
| US6156574A (en) | 1997-06-23 | 2000-12-05 | The Rockefeller University | Methods of performing gene trapping in bacterial and bacteriophage-derived artificial chromosomes and use thereof |
| US6143566A (en) | 1997-06-23 | 2000-11-07 | The Rockfeller University | Methods of performing homologous recombination based modification of nucleic acids in recombination deficient cells and use of the modified nucleic acid products thereof |
| US6136952A (en) | 1997-06-25 | 2000-10-24 | University Of Washington | Human jagged polypeptide, encoding nucleic acids and methods of use |
| US6207648B1 (en) | 1997-07-24 | 2001-03-27 | Trustees Of Boston University | Methods of using cytochrome P450 reductase for the enhancement of P450-based anti-cancer gene therapy |
| US7056703B2 (en) | 1997-08-06 | 2006-06-06 | Diversa Corporation | Polypeptides having polymerase activity and methods of use thereof |
| US6855365B2 (en) | 1997-08-13 | 2005-02-15 | Diversa Corporation | Recombinant bacterial phytases and uses thereof |
| US6090584A (en) | 1997-08-21 | 2000-07-18 | University Technologies International Inc. | Baculovirus artificial chromosomes and methods of use |
| US5874259A (en) | 1997-11-21 | 1999-02-23 | Wisconsin Alumni Research Foundation | Conditionally amplifiable BAC vector |
| US6485910B1 (en) | 1998-02-09 | 2002-11-26 | Incyte Genomics, Inc. | Ras association domain containing protein |
| US6277621B1 (en) | 1998-02-26 | 2001-08-21 | Medigene, Inc. | Artificial chromosome constructs containing foreign nucleic acid sequences |
| GB9807520D0 (en) | 1998-04-09 | 1998-06-10 | Univ Wales Medicine | Modified biological material |
| US6183957B1 (en) | 1998-04-16 | 2001-02-06 | Institut Pasteur | Method for isolating a polynucleotide of interest from the genome of a mycobacterium using a BAC-based DNA library application to the detection of mycobacteria |
| US5981225A (en) | 1998-04-16 | 1999-11-09 | Baylor College Of Medicine | Gene transfer vector, recombinant adenovirus particles containing the same, method for producing the same and method of use of the same |
| GB9809280D0 (en) | 1998-04-30 | 1998-07-01 | Rpms Technology Ltd | Immunosupression |
| WO1999057307A1 (de) | 1998-05-06 | 1999-11-11 | Genprofile Ag | Verfahren zur nicht-radioaktiven detektion von membran-gebundenen nukleinsäuren und testkit |
| US6723564B2 (en) | 1998-05-07 | 2004-04-20 | Sequenom, Inc. | IR MALDI mass spectrometry of nucleic acids using liquid matrices |
| US6004804A (en) | 1998-05-12 | 1999-12-21 | Kimeragen, Inc. | Non-chimeric mutational vectors |
| WO1999058664A1 (en) | 1998-05-14 | 1999-11-18 | Whitehead Institute For Biomedical Research | Solid phase technique for selectively isolating nucleic acids |
| AUPP388298A0 (en) | 1998-06-03 | 1998-06-25 | Polychip Pharmaceuticals Pty Ltd | Precursers of pharmaceutical compounds |
| US6413776B1 (en) | 1998-06-12 | 2002-07-02 | Galapagos Geonomics N.V. | High throughput screening of gene function using adenoviral libraries for functional genomics applications |
| JP2002519029A (ja) | 1998-06-29 | 2002-07-02 | インサイト・ファーマスーティカルズ・インコーポレイテッド | アポトーシス関連分子 |
| ES2375266T3 (es) | 1998-07-21 | 2012-02-28 | Millipore Corporation | Un polinucleótido que comprende un elemento de apertura de cromatina ubicuo (ucoe). |
| AU5217599A (en) | 1998-07-27 | 2000-02-21 | Genotypes, Inc. | Automatic eukaryotic artificial chromosome vector |
| HK1044174A1 (zh) | 1998-08-11 | 2002-10-11 | 夏威夷大学 | 通过胞质内精子注射进行哺乳动物基因转移 |
| US6673909B1 (en) | 1998-08-25 | 2004-01-06 | The General Hospital Corporation | Oligonucleotides for dysferlin, a gene mutated in distal myopathy and limb girdle muscular dystrophy |
| US6632934B1 (en) | 1998-09-30 | 2003-10-14 | Board Of Regents, The University Of Texas System | MORC gene compositions and methods of use |
| GB9821193D0 (en) | 1998-09-30 | 1998-11-25 | Medical Res Council | Mammalian artificial chromosomes and uses thereof |
| US6743906B1 (en) | 1998-10-02 | 2004-06-01 | Board Of Regents, The University Of Texas | PPP2R1B is a tumor suppressor |
| GB9825555D0 (en) | 1998-11-20 | 1999-01-13 | Imp College Innovations Ltd | Suppression of xenotransplant rejection |
| EP1153136A2 (en) | 1998-12-09 | 2001-11-14 | The General Hospital Corporation | Enhanced packaging of herpes virus amplicons and generation of recombinant virus vectors |
| CA2357677A1 (en) | 1999-01-07 | 2000-07-13 | Incyte Pharmaceuticals, Inc. | Insulin-synthesis genes |
| US20020015950A1 (en) | 1999-07-07 | 2002-02-07 | Karen Anne Jones | Atherosclerosis-associated genes |
| US20020012660A1 (en) | 1999-03-04 | 2002-01-31 | Alan Colman | Method of preparing a somatic cells for nuclear transfer |
| NZ514620A (en) | 1999-03-04 | 2004-04-30 | Ppl Therapeutics Scotland Ltd | Genetic modification of somatic cells and uses thereof |
| GB9909446D0 (en) | 1999-04-23 | 1999-06-23 | Medical Res Council | Vector |
| US6544768B1 (en) | 1999-05-11 | 2003-04-08 | Cornell Research Foundation, Inc. | Mammalian soluble adenylyl cyclase |
| US6284882B1 (en) | 1999-06-10 | 2001-09-04 | Abbott Laboratories | Myostatin gene promoter and inhibition of activation thereof |
| FR2795093B1 (fr) | 1999-06-21 | 2003-08-22 | Inst Rech Developpement Ird | Moyens pour l'identification du locus d'un gene majeur de la resistance au virus de la panachure jaune du riz et leurs applications |
| JP2003180356A (ja) | 1999-07-09 | 2003-07-02 | Mitsubishi Chemicals Corp | アトピー遺伝子 |
| WO2001005962A1 (en) | 1999-07-20 | 2001-01-25 | The Rockefeller University | Conditional homologous recombination of large genomic vector inserts |
| US6475752B1 (en) | 1999-07-30 | 2002-11-05 | Incyte Genomics, Inc. | Mammalian imidazoline receptor |
| US7074983B2 (en) * | 1999-11-19 | 2006-07-11 | Kirin Beer Kabushiki Kaisha | Transgenic bovine comprising human immunoglobulin loci and producing human immunoglobulin |
| US7414170B2 (en) * | 1999-11-19 | 2008-08-19 | Kirin Beer Kabushiki Kaisha | Transgenic bovines capable of human antibody production |
| WO2001035735A1 (en) * | 1999-11-19 | 2001-05-25 | Hematech, Llc | Production of ungulates, preferably bovines that produce human immunoglobulins |
| ES2170622B1 (es) | 1999-12-03 | 2004-05-16 | Consejo Superior De Investigaciones Cientificas | Clones y vectores infectivos derivados de coronavirus y sus aplicaciones. |
| AUPQ462599A0 (en) | 1999-12-13 | 2000-01-13 | Polychip Pharmaceuticals Pty Ltd | Yeast-based process for production of l-pac |
| US20010044937A1 (en) | 1999-12-17 | 2001-11-22 | Gerald Schatten | Methods for producing transgenic animals |
| US6458561B1 (en) | 2000-03-13 | 2002-10-01 | Incyte Genomics, Inc. | Human NIM1 kinase |
| US6492577B1 (en) | 2000-03-16 | 2002-12-10 | The Regents Of The University Of California | Leafy cotyledon2 genes and their uses |
| JP2003530113A (ja) | 2000-04-07 | 2003-10-14 | フラームス・インテルウニフェルシタイル・インステイチュート・フォール・ビオテヒノロヒー・ヴェーゼットウェー | 新規な染色体性ベクターおよびその用途 |
| AU2001271383B2 (en) | 2000-06-23 | 2007-05-24 | The University Of Chicago | Methods for isolating centromere DNA |
| US6991900B2 (en) | 2000-06-28 | 2006-01-31 | California Institute Of Technology | Methods for identifying an essential gene in a prokaryotic microorganism |
| US6548256B2 (en) | 2000-07-14 | 2003-04-15 | Eppendorf 5 Prime, Inc. | DNA isolation method and kit |
| US6610006B1 (en) | 2000-07-25 | 2003-08-26 | C. R. Bard, Inc. | Implantable prosthesis |
| US6730500B1 (en) | 2000-08-30 | 2004-05-04 | Zymogenetics, Inc. | Methods for generating a continuous nucleotide sequence from noncontiguous nucleotide sequences |
| US20020049986A1 (en) | 2000-10-10 | 2002-04-25 | Steven Farber | High throughput genetic screening of lipid and cholesterol processing using fluorescent compounds |
| US6692954B1 (en) | 2000-11-03 | 2004-02-17 | The Scripps Research Institute | Generation of human cytomegalovirus yeast artificial chromosome recombinants |
| NZ525664A (en) | 2000-11-17 | 2008-08-29 | Kirin Holdings Kk | Expression of xenogenous (human) immunoglobulins in cloned, transgenic ungulates |
| US6448041B1 (en) | 2000-12-18 | 2002-09-10 | Incyte Genomics, Inc. | Colon cancer marker |
| CA2474161C (en) | 2001-01-25 | 2012-03-27 | Evolva Ltd. | Concatemers of differentially expressed multiple genes |
| WO2002059330A2 (en) | 2001-01-25 | 2002-08-01 | Evolva Biotech A/S | Artificial chromosomes comprising concatemers of expressible nucleotide sequences |
| WO2002061073A2 (en) | 2001-01-30 | 2002-08-08 | Thomas Jefferson University | Mutwnt fish for genetic screebibg of lipid and cholesterol metabolism |
| US20020108132A1 (en) | 2001-02-02 | 2002-08-08 | Avigenics Inc. | Production of a monoclonal antibody by a transgenic chicken |
| US7323336B2 (en) | 2001-02-21 | 2008-01-29 | Verenium Corporation | Enzymes having alpha amylase activity and methods of use thereof |
| EP1409676A2 (en) | 2001-03-07 | 2004-04-21 | Andre Schuh | Cd109 nucleic acid molecules polypeptides and methods of use |
| US6936469B2 (en) | 2001-03-22 | 2005-08-30 | Chromos Molecular Systems Inc. | Methods for delivering nucleic acid molecules into cells and assessment thereof |
| US20030186390A1 (en) | 2001-03-22 | 2003-10-02 | De Jong Gary | Methods for delivering nucleic acid molecules into cells and assessment thereof |
| WO2002076508A1 (en) | 2001-03-22 | 2002-10-03 | Chromos Molecular Systems, Inc. | Methods for delivering nucleic acid molecules into cells and assessment thereof |
| US6455026B1 (en) | 2001-03-23 | 2002-09-24 | Agy Therapeutics, Inc. | Use of protein tyrosine phosphatase zeta as a biomolecular target in the treatment and visualization of brain tumors |
| US20040245317A1 (en) | 2001-04-06 | 2004-12-09 | Vladimir Larionov | Artificial chromosomes that can shuttle between bacteria yeast and mammalian cells |
| US6472177B1 (en) | 2001-04-23 | 2002-10-29 | Wisconsin Alumni Research Foundation | Expression vector with dual control of replication and transcription |
| EP1385859A2 (en) | 2001-05-10 | 2004-02-04 | Baylor College Of Medicine | Compositions and methods for array-based genomic nucleic acid analysis of biological molecules |
| AU2002309063B8 (en) | 2001-05-11 | 2008-04-24 | Kyowa Kirin Co., Ltd. | Artificial human chromosome containing human antibody lambda light chain gene |
| IL158885A0 (en) | 2001-05-30 | 2004-05-12 | Chromos Molecular Systems Inc | Plant artificial chromosomes, uses thereof and methods of preparing plant artificial chromosomes |
| JP4489424B2 (ja) | 2001-05-30 | 2010-06-23 | グラクソ グループ リミテッド | 染色体に基くプラットホーム |
| WO2002101044A2 (en) | 2001-06-11 | 2002-12-19 | Janssen Pharmaceutica N.V. | Brain expressed gene and protein associated with bipolar disorder |
| US6638722B2 (en) | 2001-06-13 | 2003-10-28 | Invitrogen Corporation | Method for rapid amplification of DNA |
| WO2003006610A2 (en) | 2001-07-09 | 2003-01-23 | Diversa Corporation | Thermostable phosphatases and methods of making and using them |
| JP2005512532A (ja) | 2001-08-03 | 2005-05-12 | ディヴァーサ コーポレイション | P450酵素、それらをコードした核酸及びそれらの作製と使用 |
| CA2456229A1 (en) | 2001-08-03 | 2003-02-13 | Diversa Corporation | Epoxide hydrolases, nucleic acids encoding them and methods for making and using them |
| WO2003020898A2 (en) | 2001-08-30 | 2003-03-13 | Spectral Genomics, Inc. | Arrays comprising pre-labeled biological molecules and methods for making and using these arrays |
| EP1430151A1 (en) | 2001-09-17 | 2004-06-23 | Janssen Pharmaceutica N.V. | Brain expressed cap-2 gene and protein associated with bipolar disorder |
| US7351529B2 (en) | 2001-09-27 | 2008-04-01 | Perkinelmer Las, Inc. | Methods for detecting genetic mosaicisms using arrays |
| CA2463725A1 (en) | 2001-10-12 | 2003-11-06 | Spectral Genomics, Inc. | Compilations of nucleic acids and arrays and methods of using them |
| ES2645563T3 (es) * | 2001-11-30 | 2017-12-05 | Amgen Fremont Inc. | Animales transgénicos que portan genes de cadena ligera de Ig humana |
| US20030124542A1 (en) | 2001-12-28 | 2003-07-03 | Spectral Genomics, Inc. | Methods for mapping the chromosomal loci of genes expressed by a cell |
| WO2003057849A2 (en) | 2002-01-04 | 2003-07-17 | Stanford University | Telomere-encoding synthetic dna nanocircles, and their use for the elongation of telomere repeats |
| CA2474567A1 (en) | 2002-01-28 | 2003-08-07 | Diversa Corporation | Amidases, nucleic acids encoding them and methods for making and using them |
| JP2003225089A (ja) * | 2002-02-04 | 2003-08-12 | National Institute Of Agrobiological Sciences | ブタrag−1遺伝子およびその利用 |
| US7585956B2 (en) | 2002-03-04 | 2009-09-08 | The Texas A & M University System | Quantitative trait loci and somatostatin |
| DE60333001D1 (de) | 2002-04-10 | 2010-07-29 | Us Gov Health & Human Serv | Vac-bac-shuttlevektor-system |
| WO2003093469A2 (en) | 2002-05-01 | 2003-11-13 | Chromos Molecular Systems, Inc. | Methods for delivering nucleic acid molecules into cells and assessment thereof |
| EP1513397B1 (en) | 2002-05-17 | 2010-04-14 | Kyowa Hakko Kirin Co., Ltd. | Transgenic ungulates capable of human antibody production |
| WO2003101396A2 (en) | 2002-05-31 | 2003-12-11 | University Of Rochester | Helper virus-free herpesvirus amplicon particles and uses thereof |
| WO2004007750A2 (en) | 2002-07-11 | 2004-01-22 | Diversa Corporation | Monooxygenases, nucleic acids encoding them and methods for making and using them |
| EP1540008A4 (en) | 2002-07-19 | 2006-04-12 | Diversa Corp | FLUORESCENT PROTEINS, NUCLEIC ACIDS ENCODING THEM, AND METHODS OF MAKING AND USING SAME |
| DK1529110T3 (da) | 2002-08-01 | 2012-01-30 | Evolva Ltd | Fremgangsmåde til blanding af store antal af heterologe gener |
| US7518033B2 (en) | 2002-08-02 | 2009-04-14 | The General Hospital Corporation | Methods for the production of cells and mammals with desired genetic modifications |
| ES2609292T3 (es) | 2002-08-21 | 2017-04-19 | Revivicor, Inc. | Animales porcinos que carecen de cualquier expresión de alfa 1,3 galactosiltransferasa funcional |
| WO2004027075A2 (en) | 2002-09-20 | 2004-04-01 | Diversa Corporation | Chemoenzymatic methods for the synthesis of statins and stain intermediates |
| CN1717483A (zh) | 2002-10-04 | 2006-01-04 | 麒麟麦酒株式会社 | 人类人工染色体(hac)载体 |
| CA2501645A1 (en) | 2002-10-10 | 2004-04-22 | Verenium Corporation | Proteases, nucleic acids encoding them and methods for making and using them |
| EP1578937A4 (en) | 2002-11-06 | 2008-07-02 | Verenium Corp | XYLOSE ISOMERASES, NUCLEIC ACIDS ENCODING THEM AND METHODS OF MAKING AND USING THEM |
| EP1563084A4 (en) | 2002-11-08 | 2006-03-01 | Hematech Llc | TRANSGENE UNGULATES WITH REDUCED PRION PROTEIN ACTIVITY AND USES THEREOF |
| AU2002952993A0 (en) | 2002-11-29 | 2002-12-12 | The Corporation Of The Trustees Of The Order Of The Sisters Of Mercy In Queensland | Therapeutic and diagnostic agents |
| WO2004066945A2 (en) | 2003-01-24 | 2004-08-12 | Diversa Corporation | Enzymes and the nucleic acids encoding them and methods for making and using them |
| US7368284B2 (en) | 2003-06-06 | 2008-05-06 | University Of Pittsburgh | Porcine CMP-N-Acetylneuraminic acid hydroxylase gene |
| EP1685148A2 (en) | 2003-11-05 | 2006-08-02 | University Of Pittsburgh Of The Commonwealth System Of Higher Education | PORCINE ISOGLOBOSIDE 3 SYNTHASE PROTEIN, cDNA, GENOMIC ORGANIZATION, AND REGULATORY REGION |
| US7732180B2 (en) | 2004-05-07 | 2010-06-08 | University Of Pittsburgh Of The Commonwealth System Of Higher Education | Porcine Forssman synthetase protein, cDNA, genomic organization, and regulatory region |
| US20080026457A1 (en) | 2004-10-22 | 2008-01-31 | Kevin Wells | Ungulates with genetically modified immune systems |
| CA2585098C (en) | 2004-10-22 | 2018-12-18 | Revivicor, Inc. | Porcine genomic kappa and lambda light chain sequences |
-
2009
- 2009-10-27 DK DK09824080.7T patent/DK2348827T3/da active
- 2009-10-27 EP EP09824080.7A patent/EP2348827B1/en active Active
- 2009-10-27 WO PCT/US2009/062265 patent/WO2010051288A1/en not_active Ceased
- 2009-10-27 ES ES09824080.7T patent/ES2548377T3/es active Active
-
2011
- 2011-04-22 US US13/092,242 patent/US20120090039A1/en not_active Abandoned
-
2015
- 2015-03-23 US US14/665,517 patent/US10149461B2/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| EP2348827B1 (en) | 2015-07-01 |
| US10149461B2 (en) | 2018-12-11 |
| ES2548377T3 (es) | 2015-10-16 |
| EP2348827A1 (en) | 2011-08-03 |
| US20120090039A1 (en) | 2012-04-12 |
| WO2010051288A1 (en) | 2010-05-06 |
| EP2348827A4 (en) | 2012-03-28 |
| US20160278349A1 (en) | 2016-09-29 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP7308243B2 (ja) | 遺伝子改変された免疫系を有する有蹄動物 | |
| US20220056482A1 (en) | Methods for making genetic edits | |
| JP3734831B2 (ja) | 普遍的なドナー細胞及びキメラ性哺乳類宿主のための相同組換え | |
| JP3732407B2 (ja) | 染色体の改変方法 | |
| CN1486365B (zh) | 异种(人类)免疫球蛋白在克隆转基因有蹄类动物中的表达 | |
| FI121339B (fi) | Geneettisesti muunnetut hiiret ihmisen vasta-aineiden tuottamiseen, ja menetelmät niiden valmistamiseksi | |
| AU2009202105B2 (en) | Porcine animals lacking any expression of functional alpha 1,3 galactosyltransferase | |
| US11160260B2 (en) | Methods for protecting porcine fetuses from infection with porcine reproductive and respiratory syndrome virus (PRRSV) | |
| US10149461B2 (en) | Immunocompromised ungulates | |
| JP2009034106A (ja) | ヒト化免疫系を含むトランスジェニック動物 | |
| KR20180091821A (ko) | 유전적 상보성에 의한 인간화 car t-세포 및 혈소판의 조작방법 | |
| RS65691B1 (sr) | Svinja i ćelije rezistentne na virus reproduktivnog i respiratornog sindroma svinja (prrsv) koje imaju modifikovane cd163 gene | |
| JP2005504507A5 (da) | ||
| US20200205384A1 (en) | Transgenic Animals | |
| KR20230107335A (ko) | 이종이식을 위한 성장 호르몬 수용체 녹아웃을 갖는 다중-전이유전자 돼지 | |
| US20210037797A1 (en) | Inducible disease models methods of making them and use in tissue complementation | |
| AU2025208495A1 (en) | Methods for protecting porcine fetuses from infection with virus | |
| Ishida et al. | Production of a diverse repertoire of human antibodies in genetically engineered mice | |
| RU2778405C2 (ru) | Способы защиты плодов свиней от инфицирования вирусом | |
| JP2006129736A (ja) | 異種移植用豚細胞、その選抜方法及び異種移植用豚 | |
| Laible | Conference VIII | |
| Beaton | GGTA-1 targeting efficiency with a xenograft transgene | |
| HK1235224A1 (en) | Multiplex gene editing in swine |