OA12240A - Targeted chromosomal genomic alterations with modified single stranded oligonucleotides. - Google Patents

Targeted chromosomal genomic alterations with modified single stranded oligonucleotides. Download PDF

Info

Publication number: OA12240A
Authority: OA; OAPI
Prior art keywords: oligonucleotide; oligonucleotides; alteration; mutation; dna
Prior art date: 2000-03-27

Application number

OA1200200302A

Other languages

English (en)

Inventor

Howard B Gamper

Eric B Kmiec

Michael C Rice

Original Assignee

Univ Delaware

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

2000-03-27

Filing date

2001-03-27

Publication date

2006-05-10

2001-03-27 Application filed by Univ Delaware filed Critical Univ Delaware

2006-05-10 Publication of OA12240A publication Critical patent/OA12240A/en

Links

108091034117 Oligonucleotide Proteins 0.000 title claims abstract description 569
230000037442 genomic alteration Effects 0.000 title claims abstract description 5
230000002759 chromosomal effect Effects 0.000 title claims abstract description 4
JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 title abstract description 172
238000000034 method Methods 0.000 claims abstract description 38
239000000203 mixture Substances 0.000 claims abstract description 24
108090000623 proteins and genes Proteins 0.000 claims description 161
210000004027 cell Anatomy 0.000 claims description 118
108020004414 DNA Proteins 0.000 claims description 86
230000004075 alteration Effects 0.000 claims description 61
102000004169 proteins and genes Human genes 0.000 claims description 46
239000000284 extract Substances 0.000 claims description 45
241000282414 Homo sapiens Species 0.000 claims description 32
RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 claims description 28
108091032973 (ribonucleotides)n+m Proteins 0.000 claims description 23
108091028043 Nucleic acid sequence Proteins 0.000 claims description 15
230000000295 complement effect Effects 0.000 claims description 13
102000053602 DNA Human genes 0.000 claims description 8
230000002538 fungal effect Effects 0.000 claims description 6
210000005260 human cell Anatomy 0.000 claims description 4
239000008194 pharmaceutical composition Substances 0.000 claims description 4
241000283984 Rodentia Species 0.000 claims description 3
108091028664 Ribonucleotide Proteins 0.000 claims description 2
238000007385 chemical modification Methods 0.000 claims description 2
239000002336 ribonucleotide Substances 0.000 claims description 2
SGPGESCZOCHFCL-UHFFFAOYSA-N Tilisolol hydrochloride Chemical compound [Cl-].C1=CC=C2C(=O)N(C)C=C(OCC(O)C[NH2+]C(C)(C)C)C2=C1 SGPGESCZOCHFCL-UHFFFAOYSA-N 0.000 claims 8
241000288906 Primates Species 0.000 claims 2
125000002652 ribonucleotide group Chemical group 0.000 claims 1
101710163270 Nuclease Proteins 0.000 abstract description 10
230000035772 mutation Effects 0.000 description 382
208000035150 Hypercholesterolemia Diseases 0.000 description 117
208000009429 hemophilia B Diseases 0.000 description 107
201000003542 Factor VIII deficiency Diseases 0.000 description 100
210000000481 breast Anatomy 0.000 description 94
208000029664 classic familial adenomatous polyposis Diseases 0.000 description 83
230000008439 repair process Effects 0.000 description 59
239000013612 plasmid Substances 0.000 description 53
206010010099 Combined immunodeficiency Diseases 0.000 description 46
201000000582 Retinoblastoma Diseases 0.000 description 45
208000036556 autosomal recessive T cell-negative B cell-negative NK cell-negative due to adenosine deaminase deficiency severe combined immunodeficiency Diseases 0.000 description 45
238000012937 correction Methods 0.000 description 45
201000009628 adenosine deaminase deficiency Diseases 0.000 description 39
201000001441 melanoma Diseases 0.000 description 36
201000003883 Cystic fibrosis Diseases 0.000 description 35
206010006187 Breast cancer Diseases 0.000 description 34
208000026310 Breast neoplasm Diseases 0.000 description 34
208000002903 Thalassemia Diseases 0.000 description 32
230000000694 effects Effects 0.000 description 32
108020004705 Codon Proteins 0.000 description 31
208000009292 Hemophilia A Diseases 0.000 description 31
238000012986 modification Methods 0.000 description 31
235000018102 proteins Nutrition 0.000 description 31
208000031220 Hemophilia Diseases 0.000 description 30
230000004048 modification Effects 0.000 description 30
238000006243 chemical reaction Methods 0.000 description 29
208000024827 Alzheimer disease Diseases 0.000 description 28
206010028980 Neoplasm Diseases 0.000 description 28
241000196324 Embryophyta Species 0.000 description 27
238000002474 experimental method Methods 0.000 description 26
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 25
238000003556 assay Methods 0.000 description 21
201000010099 disease Diseases 0.000 description 19
229930027917 kanamycin Natural products 0.000 description 19
229960000318 kanamycin Drugs 0.000 description 19
SBUJHOSQTJFQJX-NOAMYHISSA-N kanamycin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N SBUJHOSQTJFQJX-NOAMYHISSA-N 0.000 description 19
229930182823 kanamycin A Natural products 0.000 description 19
208000011580 syndromic disease Diseases 0.000 description 19
208000001819 Crigler-Najjar Syndrome Diseases 0.000 description 18
239000013598 vector Substances 0.000 description 18
102100029470 Apolipoprotein E Human genes 0.000 description 17
201000011510 cancer Diseases 0.000 description 16
230000037433 frameshift Effects 0.000 description 16
230000002068 genetic effect Effects 0.000 description 16
230000001965 increasing effect Effects 0.000 description 15
101150118377 tet gene Proteins 0.000 description 15
101100480824 Bacillus subtilis (strain 168) tetB gene Proteins 0.000 description 14
YQYJSBFKSSDGFO-UHFFFAOYSA-N Epihygromycin Natural products OC1C(O)C(C(=O)C)OC1OC(C(=C1)O)=CC=C1C=C(C)C(=O)NC1C(O)C(O)C2OCOC2C1O YQYJSBFKSSDGFO-UHFFFAOYSA-N 0.000 description 14
101100206306 Streptomyces lividans tetM gene Proteins 0.000 description 14
230000008859 change Effects 0.000 description 14
101710095339 Apolipoprotein E Proteins 0.000 description 13
206010043391 Thalassaemia beta Diseases 0.000 description 13
208000020990 adrenal cortex carcinoma Diseases 0.000 description 13
102000052609 BRCA2 Human genes 0.000 description 12
108700020462 BRCA2 Proteins 0.000 description 12
101150008921 Brca2 gene Proteins 0.000 description 12
230000010558 Gene Alterations Effects 0.000 description 12
240000004808 Saccharomyces cerevisiae Species 0.000 description 12
235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 12
230000014509 gene expression Effects 0.000 description 12
102000039446 nucleic acids Human genes 0.000 description 12
108020004707 nucleic acids Proteins 0.000 description 12
150000007523 nucleic acids Chemical class 0.000 description 12
102100036664 Adenosine deaminase Human genes 0.000 description 11
108010054147 Hemoglobins Proteins 0.000 description 11
102000001554 Hemoglobins Human genes 0.000 description 11
238000003780 insertion Methods 0.000 description 11
230000037431 insertion Effects 0.000 description 11
235000014698 Brassica juncea var multisecta Nutrition 0.000 description 9
235000006008 Brassica napus var napus Nutrition 0.000 description 9
240000000385 Brassica napus var. napus Species 0.000 description 9
235000006618 Brassica rapa subsp oleifera Nutrition 0.000 description 9
235000004977 Brassica sinapistrum Nutrition 0.000 description 9
102100024458 Cyclin-dependent kinase inhibitor 2A Human genes 0.000 description 9
241000588724 Escherichia coli Species 0.000 description 9
231100000221 frame shift mutation induction Toxicity 0.000 description 9
239000003446 ligand Substances 0.000 description 9
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
210000005253 yeast cell Anatomy 0.000 description 9
102000036365 BRCA1 Human genes 0.000 description 8
108700020463 BRCA1 Proteins 0.000 description 8
101150072950 BRCA1 gene Proteins 0.000 description 8
108010009392 Cyclin-Dependent Kinase Inhibitor p16 Proteins 0.000 description 8
101000600434 Homo sapiens Putative uncharacterized protein encoded by MIR7-3HG Proteins 0.000 description 8
102000007330 LDL Lipoproteins Human genes 0.000 description 8
108010007622 LDL Lipoproteins Proteins 0.000 description 8
102100024640 Low-density lipoprotein receptor Human genes 0.000 description 8
102100037401 Putative uncharacterized protein encoded by MIR7-3HG Human genes 0.000 description 8
238000007792 addition Methods 0.000 description 8
238000004520 electroporation Methods 0.000 description 8
230000006870 function Effects 0.000 description 8
238000001415 gene therapy Methods 0.000 description 8
108020004999 messenger RNA Proteins 0.000 description 8
230000033607 mismatch repair Effects 0.000 description 8
238000006467 substitution reaction Methods 0.000 description 8
230000008685 targeting Effects 0.000 description 8
238000012360 testing method Methods 0.000 description 8
108010071619 Apolipoproteins Proteins 0.000 description 7
102000007592 Apolipoproteins Human genes 0.000 description 7
230000037429 base substitution Effects 0.000 description 7
210000000130 stem cell Anatomy 0.000 description 7
101150037123 APOE gene Proteins 0.000 description 6
108700028369 Alleles Proteins 0.000 description 6
206010009944 Colon cancer Diseases 0.000 description 6
108010079245 Cystic Fibrosis Transmembrane Conductance Regulator Proteins 0.000 description 6
108010014172 Factor V Proteins 0.000 description 6
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
108091005904 Hemoglobin subunit beta Proteins 0.000 description 6
108010019644 Oligodendrocyte Transcription Factor 2 Proteins 0.000 description 6
102100026058 Oligodendrocyte transcription factor 2 Human genes 0.000 description 6
102100022033 Presenilin-1 Human genes 0.000 description 6
102100022036 Presenilin-2 Human genes 0.000 description 6
208000009642 Severe combined immunodeficiency due to adenosine deaminase deficiency Diseases 0.000 description 6
KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 6
239000000074 antisense oligonucleotide Substances 0.000 description 6
238000012230 antisense oligonucleotides Methods 0.000 description 6
210000004436 artificial bacterial chromosome Anatomy 0.000 description 6
210000001106 artificial yeast chromosome Anatomy 0.000 description 6
208000005980 beta thalassemia Diseases 0.000 description 6
208000035475 disorder Diseases 0.000 description 6
238000005516 engineering process Methods 0.000 description 6
238000001727 in vivo Methods 0.000 description 6
238000011534 incubation Methods 0.000 description 6
238000002347 injection Methods 0.000 description 6
239000007924 injection Substances 0.000 description 6
210000004072 lung Anatomy 0.000 description 6
238000004519 manufacturing process Methods 0.000 description 6
239000002609 medium Substances 0.000 description 6
238000000520 microinjection Methods 0.000 description 6
210000001519 tissue Anatomy 0.000 description 6
108091093088 Amplicon Proteins 0.000 description 5
108020000948 Antisense Oligonucleotides Proteins 0.000 description 5
102100025064 Cellular tumor antigen p53 Human genes 0.000 description 5
108091026890 Coding region Proteins 0.000 description 5
102000012605 Cystic Fibrosis Transmembrane Conductance Regulator Human genes 0.000 description 5
102100034157 DNA mismatch repair protein Msh2 Human genes 0.000 description 5
208000032612 Glial tumor Diseases 0.000 description 5
206010018338 Glioma Diseases 0.000 description 5
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 5
102100021519 Hemoglobin subunit beta Human genes 0.000 description 5
101000721661 Homo sapiens Cellular tumor antigen p53 Proteins 0.000 description 5
101001134036 Homo sapiens DNA mismatch repair protein Msh2 Proteins 0.000 description 5
GRRNUXAQVGOGFE-UHFFFAOYSA-N Hygromycin-B Natural products OC1C(NC)CC(N)C(O)C1OC1C2OC3(C(C(O)C(O)C(C(N)CO)O3)O)OC2C(O)C(CO)O1 GRRNUXAQVGOGFE-UHFFFAOYSA-N 0.000 description 5
108010001831 LDL receptors Proteins 0.000 description 5
229910015837 MSH2 Inorganic materials 0.000 description 5
108010036933 Presenilin-1 Proteins 0.000 description 5
108010036908 Presenilin-2 Proteins 0.000 description 5
208000007536 Thrombosis Diseases 0.000 description 5
239000002253 acid Substances 0.000 description 5
229960000723 ampicillin Drugs 0.000 description 5
AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 5
210000004507 artificial chromosome Anatomy 0.000 description 5
230000001580 bacterial effect Effects 0.000 description 5
230000003115 biocidal effect Effects 0.000 description 5
230000015572 biosynthetic process Effects 0.000 description 5
239000003795 chemical substances by application Substances 0.000 description 5
238000010367 cloning Methods 0.000 description 5
210000004748 cultured cell Anatomy 0.000 description 5
230000002950 deficient Effects 0.000 description 5
238000006471 dimerization reaction Methods 0.000 description 5
239000012634 fragment Substances 0.000 description 5
230000004927 fusion Effects 0.000 description 5
108060003196 globin Proteins 0.000 description 5
GRRNUXAQVGOGFE-NZSRVPFOSA-N hygromycin B Chemical compound O[C@@H]1[C@@H](NC)C[C@@H](N)[C@H](O)[C@H]1O[C@H]1[C@H]2O[C@@]3([C@@H]([C@@H](O)[C@@H](O)[C@@H](C(N)CO)O3)O)O[C@H]2[C@@H](O)[C@@H](CO)O1 GRRNUXAQVGOGFE-NZSRVPFOSA-N 0.000 description 5
229940097277 hygromycin b Drugs 0.000 description 5
210000004962 mammalian cell Anatomy 0.000 description 5
239000000047 product Substances 0.000 description 5
241000894006 Bacteria Species 0.000 description 4
241000233866 Fungi Species 0.000 description 4
208000026350 Inborn Genetic disease Diseases 0.000 description 4
ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 4
241000699666 Mus <mouse, genus> Species 0.000 description 4
108091081021 Sense strand Proteins 0.000 description 4
108020005038 Terminator Codon Proteins 0.000 description 4
108700019146 Transgenes Proteins 0.000 description 4
101710148271 UDP-glucose:glycoprotein glucosyltransferase 1 Proteins 0.000 description 4
102100029152 UDP-glucuronosyltransferase 1A1 Human genes 0.000 description 4
OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 4
238000004458 analytical method Methods 0.000 description 4
238000013459 approach Methods 0.000 description 4
230000022131 cell cycle Effects 0.000 description 4
210000000349 chromosome Anatomy 0.000 description 4
238000010790 dilution Methods 0.000 description 4
239000012895 dilution Substances 0.000 description 4
108020001507 fusion proteins Proteins 0.000 description 4
102000037865 fusion proteins Human genes 0.000 description 4
238000003209 gene knockout Methods 0.000 description 4
208000016361 genetic disease Diseases 0.000 description 4
102000018146 globin Human genes 0.000 description 4
ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 4
210000005087 mononuclear cell Anatomy 0.000 description 4
231100000219 mutagenic Toxicity 0.000 description 4
230000003505 mutagenic effect Effects 0.000 description 4
239000011541 reaction mixture Substances 0.000 description 4
UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 4
239000000126 substance Substances 0.000 description 4
102100034540 Adenomatous polyposis coli protein Human genes 0.000 description 3
102000055025 Adenosine deaminases Human genes 0.000 description 3
229920001817 Agar Polymers 0.000 description 3
239000004475 Arginine Substances 0.000 description 3
238000009010 Bradford assay Methods 0.000 description 3
241000222122 Candida albicans Species 0.000 description 3
201000009030 Carcinoma Diseases 0.000 description 3
241000282693 Cercopithecidae Species 0.000 description 3
208000001333 Colorectal Neoplasms Diseases 0.000 description 3
102100021147 DNA mismatch repair protein Msh6 Human genes 0.000 description 3
101100216294 Danio rerio apoeb gene Proteins 0.000 description 3
239000006144 Dulbecco’s modiﬁed Eagle's medium Substances 0.000 description 3
108700024394 Exon Proteins 0.000 description 3
102100027685 Hemoglobin subunit alpha Human genes 0.000 description 3
208000032843 Hemorrhage Diseases 0.000 description 3
241000282412 Homo Species 0.000 description 3
101000968658 Homo sapiens DNA mismatch repair protein Msh6 Proteins 0.000 description 3
208000000563 Hyperlipoproteinemia Type II Diseases 0.000 description 3
ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 3
KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 3
KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 3
241001465754 Metazoa Species 0.000 description 3
241000234295 Musa Species 0.000 description 3
244000291473 Musa acuminata Species 0.000 description 3
102000013609 MutL Protein Homolog 1 Human genes 0.000 description 3
108010026664 MutL Protein Homolog 1 Proteins 0.000 description 3
206010061535 Ovarian neoplasm Diseases 0.000 description 3
229920002873 Polyethylenimine Polymers 0.000 description 3
241000700159 Rattus Species 0.000 description 3
108020004682 Single-Stranded DNA Proteins 0.000 description 3
229930006000 Sucrose Natural products 0.000 description 3
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 3
206010045261 Type IIa hyperlipidaemia Diseases 0.000 description 3
230000009471 action Effects 0.000 description 3
239000008272 agar Substances 0.000 description 3
201000006288 alpha thalassemia Diseases 0.000 description 3
230000000692 anti-sense effect Effects 0.000 description 3
ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 3
229960003121 arginine Drugs 0.000 description 3
235000009697 arginine Nutrition 0.000 description 3
230000000740 bleeding effect Effects 0.000 description 3
231100000504 carcinogenesis Toxicity 0.000 description 3
239000000969 carrier Substances 0.000 description 3
230000001413 cellular effect Effects 0.000 description 3
210000001072 colon Anatomy 0.000 description 3
230000034994 death Effects 0.000 description 3
230000007423 decrease Effects 0.000 description 3
229960004222 factor ix Drugs 0.000 description 3
201000001386 familial hypercholesterolemia Diseases 0.000 description 3
238000000338 in vitro Methods 0.000 description 3
230000003993 interaction Effects 0.000 description 3
239000002502 liposome Substances 0.000 description 3
230000036210 malignancy Effects 0.000 description 3
230000007246 mechanism Effects 0.000 description 3
238000005457 optimization Methods 0.000 description 3
108700025694 p53 Genes Proteins 0.000 description 3
239000013615 primer Substances 0.000 description 3
230000008569 process Effects 0.000 description 3
239000005720 sucrose Substances 0.000 description 3
239000006228 supernatant Substances 0.000 description 3
238000003786 synthesis reaction Methods 0.000 description 3
230000001225 therapeutic effect Effects 0.000 description 3
239000004474 valine Substances 0.000 description 3
230000003612 virological effect Effects 0.000 description 3
FQVLRGLGWNWPSS-BXBUPLCLSA-N (4r,7s,10s,13s,16r)-16-acetamido-13-(1h-imidazol-5-ylmethyl)-10-methyl-6,9,12,15-tetraoxo-7-propan-2-yl-1,2-dithia-5,8,11,14-tetrazacycloheptadecane-4-carboxamide Chemical compound N1C(=O)[C@@H](NC(C)=O)CSSC[C@@H](C(N)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](C)NC(=O)[C@@H]1CC1=CN=CN1 FQVLRGLGWNWPSS-BXBUPLCLSA-N 0.000 description 2
KSXTUUUQYQYKCR-LQDDAWAPSA-M 2,3-bis[[(z)-octadec-9-enoyl]oxy]propyl-trimethylazanium;chloride Chemical compound [Cl-].CCCCCCCC\C=C/CCCCCCCC(=O)OCC(C[N+](C)(C)C)OC(=O)CCCCCCC\C=C/CCCCCCCC KSXTUUUQYQYKCR-LQDDAWAPSA-M 0.000 description 2
101710169336 5'-deoxyadenosine deaminase Proteins 0.000 description 2
OLXZPDWKRNYJJZ-UHFFFAOYSA-N 5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-ol Chemical compound C1=NC=2C(N)=NC=NC=2N1C1CC(O)C(CO)O1 OLXZPDWKRNYJJZ-UHFFFAOYSA-N 0.000 description 2
108700001666 APC Genes Proteins 0.000 description 2
102100034035 Alcohol dehydrogenase 1A Human genes 0.000 description 2
102100022704 Amyloid-beta precursor protein Human genes 0.000 description 2
208000035143 Bacterial infection Diseases 0.000 description 2
241000283690 Bos taurus Species 0.000 description 2
239000002126 C01EB10 - Adenosine Substances 0.000 description 2
101150029409 CFTR gene Proteins 0.000 description 2
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
208000005623 Carcinogenesis Diseases 0.000 description 2
102000011045 Chloride Channels Human genes 0.000 description 2
108010062745 Chloride Channels Proteins 0.000 description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
108020004638 Circular DNA Proteins 0.000 description 2
241000699800 Cricetinae Species 0.000 description 2
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 2
102000012410 DNA Ligases Human genes 0.000 description 2
108010061982 DNA Ligases Proteins 0.000 description 2
102100037700 DNA mismatch repair protein Msh3 Human genes 0.000 description 2
206010012289 Dementia Diseases 0.000 description 2
102000004190 Enzymes Human genes 0.000 description 2
108090000790 Enzymes Proteins 0.000 description 2
201000006107 Familial adenomatous polyposis Diseases 0.000 description 2
102100037362 Fibronectin Human genes 0.000 description 2
108010067306 Fibronectins Proteins 0.000 description 2
206010064571 Gene mutation Diseases 0.000 description 2
101000892220 Geobacillus thermodenitrificans (strain NG80-2) Long-chain-alcohol dehydrogenase 1 Proteins 0.000 description 2
WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 2
239000004471 Glycine Substances 0.000 description 2
102100031573 Hematopoietic progenitor cell antigen CD34 Human genes 0.000 description 2
102220585101 Histone H1t_R136S_mutation Human genes 0.000 description 2
101000780443 Homo sapiens Alcohol dehydrogenase 1A Proteins 0.000 description 2
101000771674 Homo sapiens Apolipoprotein E Proteins 0.000 description 2
101001027762 Homo sapiens DNA mismatch repair protein Msh3 Proteins 0.000 description 2
101000777663 Homo sapiens Hematopoietic progenitor cell antigen CD34 Proteins 0.000 description 2
101001009007 Homo sapiens Hemoglobin subunit alpha Proteins 0.000 description 2
208000031226 Hyperlipidaemia Diseases 0.000 description 2
201000010252 Hyperlipoproteinemia Type III Diseases 0.000 description 2
208000001953 Hypotension Diseases 0.000 description 2
101150110531 MLH1 gene Proteins 0.000 description 2
TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
101150033433 Msh2 gene Proteins 0.000 description 2
235000018290 Musa x paradisiaca Nutrition 0.000 description 2
102220601944 Neutrophil elastase_C71S_mutation Human genes 0.000 description 2
206010033128 Ovarian cancer Diseases 0.000 description 2
229930182555 Penicillin Natural products 0.000 description 2
JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 2
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
208000037062 Polyps Diseases 0.000 description 2
102100038042 Retinoblastoma-associated protein Human genes 0.000 description 2
206010039491 Sarcoma Diseases 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
239000007983 Tris buffer Substances 0.000 description 2
102220549034 Tumor suppressor candidate gene 1 protein_C56S_mutation Human genes 0.000 description 2
ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 2
241000700605 Viruses Species 0.000 description 2
230000002159 abnormal effect Effects 0.000 description 2
229960005305 adenosine Drugs 0.000 description 2
208000007128 adrenocortical carcinoma Diseases 0.000 description 2
235000001014 amino acid Nutrition 0.000 description 2
229940024606 amino acid Drugs 0.000 description 2
150000001413 amino acids Chemical class 0.000 description 2
210000004102 animal cell Anatomy 0.000 description 2
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
239000005441 aurora Substances 0.000 description 2
210000003719 b-lymphocyte Anatomy 0.000 description 2
208000022362 bacterial infectious disease Diseases 0.000 description 2
230000008901 benefit Effects 0.000 description 2
230000027455 binding Effects 0.000 description 2
229960000074 biopharmaceutical Drugs 0.000 description 2
210000000988 bone and bone Anatomy 0.000 description 2
210000001185 bone marrow Anatomy 0.000 description 2
210000004556 brain Anatomy 0.000 description 2
239000000872 buffer Substances 0.000 description 2
230000036952 cancer formation Effects 0.000 description 2
208000035269 cancer or benign tumor Diseases 0.000 description 2
229940095731 candida albicans Drugs 0.000 description 2
235000011089 carbon dioxide Nutrition 0.000 description 2
125000002091 cationic group Chemical group 0.000 description 2
210000000170 cell membrane Anatomy 0.000 description 2
208000019065 cervical carcinoma Diseases 0.000 description 2
239000003153 chemical reaction reagent Substances 0.000 description 2
HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
208000029742 colonic neoplasm Diseases 0.000 description 2
150000001875 compounds Chemical class 0.000 description 2
208000035250 cutaneous malignant susceptibility to 1 melanoma Diseases 0.000 description 2
230000009089 cytolysis Effects 0.000 description 2
SUYVUBYJARFZHO-RRKCRQDMSA-N dATP Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@H]1C[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 SUYVUBYJARFZHO-RRKCRQDMSA-N 0.000 description 2
SUYVUBYJARFZHO-UHFFFAOYSA-N dATP Natural products C1=NC=2C(N)=NC=NC=2N1C1CC(O)C(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 SUYVUBYJARFZHO-UHFFFAOYSA-N 0.000 description 2
230000007547 defect Effects 0.000 description 2
230000007812 deficiency Effects 0.000 description 2
238000013461 design Methods 0.000 description 2
238000011161 development Methods 0.000 description 2
238000003745 diagnosis Methods 0.000 description 2
238000010586 diagram Methods 0.000 description 2
238000009826 distribution Methods 0.000 description 2
239000003814 drug Substances 0.000 description 2
210000002308 embryonic cell Anatomy 0.000 description 2
210000001671 embryonic stem cell Anatomy 0.000 description 2
108010048367 enhanced green fluorescent protein Proteins 0.000 description 2
230000002255 enzymatic effect Effects 0.000 description 2
230000010437 erythropoiesis Effects 0.000 description 2
238000000605 extraction Methods 0.000 description 2
201000007741 female breast cancer Diseases 0.000 description 2
201000002276 female breast carcinoma Diseases 0.000 description 2
230000035558 fertility Effects 0.000 description 2
210000002950 fibroblast Anatomy 0.000 description 2
239000000499 gel Substances 0.000 description 2
235000013922 glutamic acid Nutrition 0.000 description 2
239000004220 glutamic acid Substances 0.000 description 2
238000002744 homologous recombination Methods 0.000 description 2
230000006801 homologous recombination Effects 0.000 description 2
230000001976 improved effect Effects 0.000 description 2
230000006872 improvement Effects 0.000 description 2
230000001939 inductive effect Effects 0.000 description 2
238000001802 infusion Methods 0.000 description 2
230000005764 inhibitory process Effects 0.000 description 2
NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
238000001990 intravenous administration Methods 0.000 description 2
210000003734 kidney Anatomy 0.000 description 2
210000004185 liver Anatomy 0.000 description 2
208000020816 lung neoplasm Diseases 0.000 description 2
210000004698 lymphocyte Anatomy 0.000 description 2
210000000723 mammalian artificial chromosome Anatomy 0.000 description 2
101150013854 mutS gene Proteins 0.000 description 2
231100000350 mutagenesis Toxicity 0.000 description 2
238000002703 mutagenesis Methods 0.000 description 2
208000002154 non-small cell lung carcinoma Diseases 0.000 description 2
238000002515 oligonucleotide synthesis Methods 0.000 description 2
230000002611 ovarian Effects 0.000 description 2
210000001672 ovary Anatomy 0.000 description 2
229910052760 oxygen Inorganic materials 0.000 description 2
239000001301 oxygen Substances 0.000 description 2
239000002245 particle Substances 0.000 description 2
230000037361 pathway Effects 0.000 description 2
108010027841 pegademase bovine Proteins 0.000 description 2
239000008188 pellet Substances 0.000 description 2
229940049954 penicillin Drugs 0.000 description 2
230000035699 permeability Effects 0.000 description 2
YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 2
239000002953 phosphate buffered saline Substances 0.000 description 2
238000007747 plating Methods 0.000 description 2
238000006116 polymerization reaction Methods 0.000 description 2
102000054765 polymorphisms of proteins Human genes 0.000 description 2
108091033319 polynucleotide Proteins 0.000 description 2
ZCCUUQDIBDJBTK-UHFFFAOYSA-N psoralen Chemical compound C1=C2OC(=O)C=CC2=CC2=C1OC=C2 ZCCUUQDIBDJBTK-UHFFFAOYSA-N 0.000 description 2
230000006798 recombination Effects 0.000 description 2
238000005215 recombination Methods 0.000 description 2
238000011160 research Methods 0.000 description 2
108091008146 restriction endonucleases Proteins 0.000 description 2
230000002441 reversible effect Effects 0.000 description 2
102220206258 rs1057521785 Human genes 0.000 description 2
238000012163 sequencing technique Methods 0.000 description 2
239000011780 sodium chloride Substances 0.000 description 2
239000000243 solution Substances 0.000 description 2
239000000600 sorbitol Substances 0.000 description 2
ATHGHQPFGPMSJY-UHFFFAOYSA-N spermidine Chemical compound NCCCCNCCCN ATHGHQPFGPMSJY-UHFFFAOYSA-N 0.000 description 2
229960005322 streptomycin Drugs 0.000 description 2
239000000758 substrate Substances 0.000 description 2
208000024891 symptom Diseases 0.000 description 2
238000002560 therapeutic procedure Methods 0.000 description 2
238000012546 transfer Methods 0.000 description 2
230000009261 transgenic effect Effects 0.000 description 2
238000011282 treatment Methods 0.000 description 2
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 2
241000701161 unidentified adenovirus Species 0.000 description 2
206010046766 uterine cancer Diseases 0.000 description 2
239000013603 viral vector Substances 0.000 description 2
DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 2
101150084750 1 gene Proteins 0.000 description 1
101150029062 15 gene Proteins 0.000 description 1
VGONTNSXDCQUGY-RRKCRQDMSA-N 2'-deoxyinosine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(N=CNC2=O)=C2N=C1 VGONTNSXDCQUGY-RRKCRQDMSA-N 0.000 description 1
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 1
VXGRJERITKFWPL-UHFFFAOYSA-N 4',5'-Dihydropsoralen Natural products C1=C2OC(=O)C=CC2=CC2=C1OCC2 VXGRJERITKFWPL-UHFFFAOYSA-N 0.000 description 1
OOXNYFKPOPJIOT-UHFFFAOYSA-N 5-(3-bromophenyl)-7-(6-morpholin-4-ylpyridin-3-yl)pyrido[2,3-d]pyrimidin-4-amine;dihydrochloride Chemical compound Cl.Cl.C=12C(N)=NC=NC2=NC(C=2C=NC(=CC=2)N2CCOCC2)=CC=1C1=CC=CC(Br)=C1 OOXNYFKPOPJIOT-UHFFFAOYSA-N 0.000 description 1
RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
208000004804 Adenomatous Polyps Diseases 0.000 description 1
102220468495 Adenomatous polyposis coli protein_A1184P_mutation Human genes 0.000 description 1
102220468494 Adenomatous polyposis coli protein_P1176L_mutation Human genes 0.000 description 1
102220467716 Adenomatous polyposis coli protein_R1348W_mutation Human genes 0.000 description 1
102220468442 Adenomatous polyposis coli protein_S722G_mutation Human genes 0.000 description 1
102220468439 Adenomatous polyposis coli protein_S784T_mutation Human genes 0.000 description 1
108700040115 Adenosine deaminases Proteins 0.000 description 1
102100032534 Adenosine kinase Human genes 0.000 description 1
108010076278 Adenosine kinase Proteins 0.000 description 1
108010088751 Albumins Proteins 0.000 description 1
102000009027 Albumins Human genes 0.000 description 1
102220486134 Alpha-galactosidase A_C56Y_mutation Human genes 0.000 description 1
101710137189 Amyloid-beta A4 protein Proteins 0.000 description 1
101710151993 Amyloid-beta precursor protein Proteins 0.000 description 1
241000219194 Arabidopsis Species 0.000 description 1
102220542419 Aspartoacylase_C152W_mutation Human genes 0.000 description 1
201000001320 Atherosclerosis Diseases 0.000 description 1
108700040618 BRCA1 Genes Proteins 0.000 description 1
102220562168 Band 3 anion transport protein_G455E_mutation Human genes 0.000 description 1
102220553132 Beta-hexosaminidase subunit alpha_G455R_mutation Human genes 0.000 description 1
108010039209 Blood Coagulation Factors Proteins 0.000 description 1
102000015081 Blood Coagulation Factors Human genes 0.000 description 1
206010005949 Bone cancer Diseases 0.000 description 1
208000018084 Bone neoplasm Diseases 0.000 description 1
102220484582 C-type lectin domain family 4 member K_V278A_mutation Human genes 0.000 description 1
101150041972 CDKN2A gene Proteins 0.000 description 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
206010007134 Candida infections Diseases 0.000 description 1
102220584278 Cellular tumor antigen p53_G59D_mutation Human genes 0.000 description 1
102220594111 Cellular tumor antigen p53_R282H_mutation Human genes 0.000 description 1
108091092236 Chimeric RNA Proteins 0.000 description 1
241000282552 Chlorocebus aethiops Species 0.000 description 1
108010077544 Chromatin Proteins 0.000 description 1
102100022641 Coagulation factor IX Human genes 0.000 description 1
206010053567 Coagulopathies Diseases 0.000 description 1
101100007328 Cocos nucifera COS-1 gene Proteins 0.000 description 1
108020004394 Complementary RNA Proteins 0.000 description 1
241000699802 Cricetulus griseus Species 0.000 description 1
102220503565 Cyclin-dependent kinase inhibitor 2A_E33D_mutation Human genes 0.000 description 1
102220503734 Cyclin-dependent kinase inhibitor 2A_L16P_mutation Human genes 0.000 description 1
102220504545 Cyclin-dependent kinase inhibitor 2A_L62P_mutation Human genes 0.000 description 1
102220593029 Cyclin-dependent kinase inhibitor 2A_L97R_mutation Human genes 0.000 description 1
102220504543 Cyclin-dependent kinase inhibitor 2A_N71K_mutation Human genes 0.000 description 1
102220504499 Cyclin-dependent kinase inhibitor 2A_P81L_mutation Human genes 0.000 description 1
102100023419 Cystic fibrosis transmembrane conductance regulator Human genes 0.000 description 1
102220610495 DNA mismatch repair protein Msh3_C88S_mutation Human genes 0.000 description 1
239000003155 DNA primer Substances 0.000 description 1
102100029588 Deoxycytidine kinase Human genes 0.000 description 1
108010033174 Deoxycytidine kinase Proteins 0.000 description 1
241000702421 Dependoparvovirus Species 0.000 description 1
206010012735 Diarrhoea Diseases 0.000 description 1
206010012741 Diarrhoea haemorrhagic Diseases 0.000 description 1
101100260709 Drosophila melanogaster tin gene Proteins 0.000 description 1
102220569509 Dual serine/threonine and tyrosine protein kinase_D200G_mutation Human genes 0.000 description 1
208000034599 Dysbetalipoproteinemia Diseases 0.000 description 1
102220531203 Dyslexia-associated protein KIAA0319-like protein_C74G_mutation Human genes 0.000 description 1
206010058314 Dysplasia Diseases 0.000 description 1
102220510437 E3 ubiquitin-protein ligase NHLRC1_C68Y_mutation Human genes 0.000 description 1
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 1
102220498716 Ecotropic viral integration site 5 protein homolog_D82V_mutation Human genes 0.000 description 1
244000148064 Enicostema verticillatum Species 0.000 description 1
108091092566 Extrachromosomal DNA Proteins 0.000 description 1
108010076282 Factor IX Proteins 0.000 description 1
108010054218 Factor VIII Proteins 0.000 description 1
102000001690 Factor VIII Human genes 0.000 description 1
206010016654 Fibrosis Diseases 0.000 description 1
229920001917 Ficoll Polymers 0.000 description 1
206010017533 Fungal infection Diseases 0.000 description 1
101150094690 GAL1 gene Proteins 0.000 description 1
102100028501 Galanin peptides Human genes 0.000 description 1
102220590573 Gap junction beta-1 protein_H94Y_mutation Human genes 0.000 description 1
241000976806 Genea <ascomycete fungus> Species 0.000 description 1
102220509813 General transcription factor II-I_Q71E_mutation Human genes 0.000 description 1
208000009139 Gilbert Disease Diseases 0.000 description 1
208000022412 Gilbert syndrome Diseases 0.000 description 1
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
244000068988 Glycine max Species 0.000 description 1
235000010469 Glycine max Nutrition 0.000 description 1
239000005562 Glyphosate Substances 0.000 description 1
101150056393 H6 gene Proteins 0.000 description 1
102000007513 Hemoglobin A Human genes 0.000 description 1
108010085682 Hemoglobin A Proteins 0.000 description 1
108091005902 Hemoglobin subunit alpha Proteins 0.000 description 1
208000017095 Hereditary nonpolyposis colon cancer Diseases 0.000 description 1
208000016096 Hereditary retinoblastoma Diseases 0.000 description 1
102220583204 Histone H1t_D82G_mutation Human genes 0.000 description 1
101100383161 Homo sapiens CDKN2A gene Proteins 0.000 description 1
101000980932 Homo sapiens Cyclin-dependent kinase inhibitor 2A Proteins 0.000 description 1
101000620735 Homo sapiens DNA repair protein RAD51 homolog 1 Proteins 0.000 description 1
101100121078 Homo sapiens GAL gene Proteins 0.000 description 1
101001076408 Homo sapiens Interleukin-6 Proteins 0.000 description 1
101100184207 Homo sapiens MLH1 gene Proteins 0.000 description 1
101100346542 Homo sapiens MSH2 gene Proteins 0.000 description 1
101100292219 Homo sapiens MSH6 gene Proteins 0.000 description 1
101000742859 Homo sapiens Retinoblastoma-associated protein Proteins 0.000 description 1
101000766306 Homo sapiens Serotransferrin Proteins 0.000 description 1
101000640793 Homo sapiens UDP-galactose translocator Proteins 0.000 description 1
206010061218 Inflammation Diseases 0.000 description 1
229930010555 Inosine Natural products 0.000 description 1
UGQMRVRMYYASKQ-KQYNXXCUSA-N Inosine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(O)=C2N=C1 UGQMRVRMYYASKQ-KQYNXXCUSA-N 0.000 description 1
102000004877 Insulin Human genes 0.000 description 1
108090001061 Insulin Proteins 0.000 description 1
102220489721 Integrin beta-1_C73S_mutation Human genes 0.000 description 1
206010023126 Jaundice Diseases 0.000 description 1
108010025815 Kanamycin Kinase Proteins 0.000 description 1
102220534110 Kelch-like ECH-associated protein 1_C23Y_mutation Human genes 0.000 description 1
102220568582 LIM and senescent cell antigen-like-containing domain protein 2_N92K_mutation Human genes 0.000 description 1
ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
102220508731 Leucine-rich repeat transmembrane neuronal protein 1_D525N_mutation Human genes 0.000 description 1
NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 description 1
241000209510 Liliopsida Species 0.000 description 1
206010058467 Lung neoplasm malignant Diseases 0.000 description 1
206010025323 Lymphomas Diseases 0.000 description 1
239000004472 Lysine Substances 0.000 description 1
102220620432 Lysosomal acid glucosylceramidase_C62S_mutation Human genes 0.000 description 1
102220553275 Lysosomal acid glucosylceramidase_E80K_mutation Human genes 0.000 description 1
101150102506 MSH3 gene Proteins 0.000 description 1
241000701076 Macacine alphaherpesvirus 1 Species 0.000 description 1
208000004059 Male Breast Neoplasms Diseases 0.000 description 1
241000124008 Mammalia Species 0.000 description 1
102220517617 Methyl-CpG-binding domain protein 3-like 2B_N2D_mutation Human genes 0.000 description 1
102220531969 Microtubule-associated protein RP/EB family member 1_D283E_mutation Human genes 0.000 description 1
201000005979 Muir-Torre Syndrome Diseases 0.000 description 1
241001529936 Murinae Species 0.000 description 1
208000031888 Mycoses Diseases 0.000 description 1
102220565064 N-acetyltransferase 9_C56R_mutation Human genes 0.000 description 1
102220560484 NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 9, mitochondrial_E17Q_mutation Human genes 0.000 description 1
102220520043 NADPH-cytochrome P450 reductase_A284P_mutation Human genes 0.000 description 1
244000061176 Nicotiana tabacum Species 0.000 description 1
235000002637 Nicotiana tabacum Nutrition 0.000 description 1
208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 1
208000016107 Non-hereditary retinoblastoma Diseases 0.000 description 1
102000007999 Nuclear Proteins Human genes 0.000 description 1
108010089610 Nuclear Proteins Proteins 0.000 description 1
108091005461 Nucleic proteins Proteins 0.000 description 1
102220492808 Olfactory receptor 8D1_C127W_mutation Human genes 0.000 description 1
102100026056 Oligodendrocyte transcription factor 3 Human genes 0.000 description 1
101710195927 Oligodendrocyte transcription factor 3 Proteins 0.000 description 1
102220516443 Oncostatin-M_C139G_mutation Human genes 0.000 description 1
102220517511 POTE ankyrin domain family member B2_D147Y_mutation Human genes 0.000 description 1
102220515106 Peroxisomal sarcosine oxidase_E11V_mutation Human genes 0.000 description 1
102220637155 Phenylalanine-4-hydroxylase_E390G_mutation Human genes 0.000 description 1
102220469104 Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN_C71Y_mutation Human genes 0.000 description 1
239000004698 Polyethylene Substances 0.000 description 1
102220553089 Proenkephalin-A_F77Y_mutation Human genes 0.000 description 1
ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
108010029485 Protein Isoforms Proteins 0.000 description 1
102000001708 Protein Isoforms Human genes 0.000 description 1
102220639715 Protein LEG1 homolog_C308G_mutation Human genes 0.000 description 1
102220526774 Protein MTSS 1_D56E_mutation Human genes 0.000 description 1
206010037075 Protozoal infections Diseases 0.000 description 1
102220618244 Putative uncharacterized protein UNQ9370/PRO34162_Y354V_mutation Human genes 0.000 description 1
230000026279 RNA modification Effects 0.000 description 1
230000004570 RNA-binding Effects 0.000 description 1
102220493928 RNA-binding protein 38_A200D_mutation Human genes 0.000 description 1
MUPFEKGTMRGPLJ-RMMQSMQOSA-N Raffinose Natural products O(C[C@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](O[C@@]2(CO)[C@H](O)[C@@H](O)[C@@H](CO)O2)O1)[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 MUPFEKGTMRGPLJ-RMMQSMQOSA-N 0.000 description 1
101150002130 Rb1 gene Proteins 0.000 description 1
108010055016 Rec A Recombinases Proteins 0.000 description 1
102000001218 Rec A Recombinases Human genes 0.000 description 1
108091081062 Repeated sequence (DNA) Proteins 0.000 description 1
102220491246 Replication stress response regulator SDE2_D200Y_mutation Human genes 0.000 description 1
108700008625 Reporter Genes Proteins 0.000 description 1
101710124357 Retinoblastoma-associated protein Proteins 0.000 description 1
102220643717 Retinoblastoma-associated protein_A635P_mutation Human genes 0.000 description 1
102220644050 Retinoblastoma-associated protein_C706Y_mutation Human genes 0.000 description 1
102220643667 Retinoblastoma-associated protein_L657P_mutation Human genes 0.000 description 1
102220643663 Retinoblastoma-associated protein_L662P_mutation Human genes 0.000 description 1
102220643679 Retinoblastoma-associated protein_Q685P_mutation Human genes 0.000 description 1
102220645614 Retinoblastoma-associated protein_R358G_mutation Human genes 0.000 description 1
102000000505 Ribonucleotide Reductases Human genes 0.000 description 1
108010041388 Ribonucleotide Reductases Proteins 0.000 description 1
230000018199 S phase Effects 0.000 description 1
241000235070 Saccharomyces Species 0.000 description 1
MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
208000021712 Soft tissue sarcoma Diseases 0.000 description 1
244000300264 Spinacia oleracea Species 0.000 description 1
235000009337 Spinacia oleracea Nutrition 0.000 description 1
102220574633 Spindlin-1_W72R_mutation Human genes 0.000 description 1
206010041954 Starvation Diseases 0.000 description 1
102220614781 Sushi, nidogen and EGF-like domain-containing protein 1_H1299R_mutation Human genes 0.000 description 1
102220546329 T-cell surface glycoprotein CD1a_C68W_mutation Human genes 0.000 description 1
210000001744 T-lymphocyte Anatomy 0.000 description 1
102220521920 THAP domain-containing protein 1_R29P_mutation Human genes 0.000 description 1
102220521923 THAP domain-containing protein 1_R29Q_mutation Human genes 0.000 description 1
206010043390 Thalassaemia alpha Diseases 0.000 description 1
RYYWUUFWQRZTIU-UHFFFAOYSA-N Thiophosphoric acid Chemical group OP(O)(S)=O RYYWUUFWQRZTIU-UHFFFAOYSA-N 0.000 description 1
102000036693 Thrombopoietin Human genes 0.000 description 1
108010041111 Thrombopoietin Proteins 0.000 description 1
102000040945 Transcription factor Human genes 0.000 description 1
108091023040 Transcription factor Proteins 0.000 description 1
235000021307 Triticum Nutrition 0.000 description 1
244000098338 Triticum aestivum Species 0.000 description 1
229920004890 Triton X-100 Polymers 0.000 description 1
102000001742 Tumor Suppressor Proteins Human genes 0.000 description 1
108010040002 Tumor Suppressor Proteins Proteins 0.000 description 1
102220541304 Tumor necrosis factor receptor superfamily member 6_E272G_mutation Human genes 0.000 description 1
206010060751 Type III hyperlipidaemia Diseases 0.000 description 1
102220563343 Tyrosine-protein kinase BTK_F25S_mutation Human genes 0.000 description 1
102220573854 UDP-glucuronosyltransferase 1A1_A292V_mutation Human genes 0.000 description 1
102220575076 UDP-glucuronosyltransferase 1A1_A368T_mutation Human genes 0.000 description 1
102220573951 UDP-glucuronosyltransferase 1A1_A401P_mutation Human genes 0.000 description 1
102220573917 UDP-glucuronosyltransferase 1A1_G71R_mutation Human genes 0.000 description 1
102220573978 UDP-glucuronosyltransferase 1A1_K428E_mutation Human genes 0.000 description 1
102220575096 UDP-glucuronosyltransferase 1A1_S381R_mutation Human genes 0.000 description 1
MUPFEKGTMRGPLJ-UHFFFAOYSA-N UNPD196149 Natural products OC1C(O)C(CO)OC1(CO)OC1C(O)C(O)C(O)C(COC2C(C(O)C(O)C(CO)O2)O)O1 MUPFEKGTMRGPLJ-UHFFFAOYSA-N 0.000 description 1
244000301083 Ustilago maydis Species 0.000 description 1
235000015919 Ustilago maydis Nutrition 0.000 description 1
208000002495 Uterine Neoplasms Diseases 0.000 description 1
208000036142 Viral infection Diseases 0.000 description 1
240000008042 Zea mays Species 0.000 description 1
235000016383 Zea mays subsp huehuetenangensis Nutrition 0.000 description 1
235000002017 Zea mays subsp mays Nutrition 0.000 description 1
HMNZFMSWFCAGGW-XPWSMXQVSA-N [3-[hydroxy(2-hydroxyethoxy)phosphoryl]oxy-2-[(e)-octadec-9-enoyl]oxypropyl] (e)-octadec-9-enoate Chemical compound CCCCCCCC\C=C\CCCCCCCC(=O)OCC(COP(O)(=O)OCCO)OC(=O)CCCCCCC\C=C\CCCCCCCC HMNZFMSWFCAGGW-XPWSMXQVSA-N 0.000 description 1
210000003892 absorptive cell Anatomy 0.000 description 1
230000003213 activating effect Effects 0.000 description 1
239000013543 active substance Substances 0.000 description 1
239000002671 adjuvant Substances 0.000 description 1
208000024447 adrenal gland neoplasm Diseases 0.000 description 1
239000002115 aflatoxin B1 Substances 0.000 description 1
OQIQSTLJSLGHID-WNWIJWBNSA-N aflatoxin B1 Chemical compound C=1([C@@H]2C=CO[C@@H]2OC=1C=C(C1=2)OC)C=2OC(=O)C2=C1CCC2=O OQIQSTLJSLGHID-WNWIJWBNSA-N 0.000 description 1
229930020125 aflatoxin-B1 Natural products 0.000 description 1
239000011543 agarose gel Substances 0.000 description 1
238000011256 aggressive treatment Methods 0.000 description 1
239000003708 ampul Substances 0.000 description 1
208000007502 anemia Diseases 0.000 description 1
238000010171 animal model Methods 0.000 description 1
238000000137 annealing Methods 0.000 description 1
239000003242 anti bacterial agent Substances 0.000 description 1
239000000427 antigen Substances 0.000 description 1
108091007433 antigens Proteins 0.000 description 1
102000036639 antigens Human genes 0.000 description 1
239000012062 aqueous buffer Substances 0.000 description 1
208000025261 autosomal dominant disease Diseases 0.000 description 1
238000003287 bathing Methods 0.000 description 1
239000011324 bead Substances 0.000 description 1
230000002146 bilateral effect Effects 0.000 description 1
201000008900 bilateral retinoblastoma Diseases 0.000 description 1
230000000903 blocking effect Effects 0.000 description 1
210000004369 blood Anatomy 0.000 description 1
239000008280 blood Substances 0.000 description 1
239000003114 blood coagulation factor Substances 0.000 description 1
210000004899 c-terminal region Anatomy 0.000 description 1
102220359803 c.10G>A Human genes 0.000 description 1
102220414119 c.1375G>A Human genes 0.000 description 1
102220350690 c.151T>C Human genes 0.000 description 1
102220411695 c.201C>A Human genes 0.000 description 1
102220364341 c.217T>C Human genes 0.000 description 1
102200089580 c.232A>C Human genes 0.000 description 1
102220378030 c.26T>G Human genes 0.000 description 1
102220350906 c.290A>C Human genes 0.000 description 1
102220353094 c.355G>A Human genes 0.000 description 1
102200081178 c.433C>T Human genes 0.000 description 1
102220361180 c.434G>T Human genes 0.000 description 1
102220411430 c.488G>A Human genes 0.000 description 1
102220363285 c.598G>A Human genes 0.000 description 1
102200025859 c.682C>T Human genes 0.000 description 1
102220425081 c.700G>T Human genes 0.000 description 1
102220360638 c.705C>A Human genes 0.000 description 1
102220357652 c.730G>A Human genes 0.000 description 1
102220370696 c.735T>A Human genes 0.000 description 1
102220359492 c.851C>A Human genes 0.000 description 1
102220352428 c.92G>A Human genes 0.000 description 1
102220398124 c.941G>T Human genes 0.000 description 1
102220348619 c.959C>G Human genes 0.000 description 1
102220353251 c.961G>A Human genes 0.000 description 1
102220515760 cAMP-dependent protein kinase inhibitor alpha_C139Y_mutation Human genes 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
239000011575 calcium Substances 0.000 description 1
239000001506 calcium phosphate Substances 0.000 description 1
229910000389 calcium phosphate Inorganic materials 0.000 description 1
235000011010 calcium phosphates Nutrition 0.000 description 1
201000003984 candidiasis Diseases 0.000 description 1
OSQPUMRCKZAIOZ-UHFFFAOYSA-N carbon dioxide;ethanol Chemical compound CCO.O=C=O OSQPUMRCKZAIOZ-UHFFFAOYSA-N 0.000 description 1
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
-1 carrier Substances 0.000 description 1
238000004113 cell culture Methods 0.000 description 1
230000006369 cell cycle progression Effects 0.000 description 1
230000003915 cell function Effects 0.000 description 1
239000006285 cell suspension Substances 0.000 description 1
230000004700 cellular uptake Effects 0.000 description 1
238000005119 centrifugation Methods 0.000 description 1
210000002230 centromere Anatomy 0.000 description 1
210000003679 cervix uteri Anatomy 0.000 description 1
235000012000 cholesterol Nutrition 0.000 description 1
210000003483 chromatin Anatomy 0.000 description 1
239000013611 chromosomal DNA Substances 0.000 description 1
230000001684 chronic effect Effects 0.000 description 1
238000003776 cleavage reaction Methods 0.000 description 1
230000035602 clotting Effects 0.000 description 1
238000012761 co-transfection Methods 0.000 description 1
201000010897 colon adenocarcinoma Diseases 0.000 description 1
239000003184 complementary RNA Substances 0.000 description 1
230000001010 compromised effect Effects 0.000 description 1
239000012141 concentrate Substances 0.000 description 1
238000012790 confirmation Methods 0.000 description 1
238000004624 confocal microscopy Methods 0.000 description 1
238000010276 construction Methods 0.000 description 1
238000011109 contamination Methods 0.000 description 1
238000012258 culturing Methods 0.000 description 1
230000001086 cytosolic effect Effects 0.000 description 1
230000006378 damage Effects 0.000 description 1
230000009615 deamination Effects 0.000 description 1
238000006481 deamination reaction Methods 0.000 description 1
230000002939 deleterious effect Effects 0.000 description 1
238000010511 deprotection reaction Methods 0.000 description 1
VGONTNSXDCQUGY-UHFFFAOYSA-N desoxyinosine Natural products C1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 VGONTNSXDCQUGY-UHFFFAOYSA-N 0.000 description 1
239000008121 dextrose Substances 0.000 description 1
239000000032 diagnostic agent Substances 0.000 description 1
239000000539 dimer Substances 0.000 description 1
230000003292 diminished effect Effects 0.000 description 1
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 1
239000012153 distilled water Substances 0.000 description 1
239000002552 dosage form Substances 0.000 description 1
229940079593 drug Drugs 0.000 description 1
238000001962 electrophoresis Methods 0.000 description 1
210000003743 erythrocyte Anatomy 0.000 description 1
241001233957 eudicotyledons Species 0.000 description 1
239000013604 expression vector Substances 0.000 description 1
239000011536 extraction buffer Substances 0.000 description 1
208000024519 eye neoplasm Diseases 0.000 description 1
201000007382 factor V deficiency Diseases 0.000 description 1
229960000301 factor viii Drugs 0.000 description 1
206010016165 failure to thrive Diseases 0.000 description 1
201000008949 familial retinoblastoma Diseases 0.000 description 1
210000004700 fetal blood Anatomy 0.000 description 1
230000004761 fibrosis Effects 0.000 description 1
108700014844 flt3 ligand Proteins 0.000 description 1
238000000799 fluorescence microscopy Methods 0.000 description 1
101150016518 for gene Proteins 0.000 description 1
229930182830 galactose Natural products 0.000 description 1
238000012239 gene modification Methods 0.000 description 1
231100000089 gene mutation induction Toxicity 0.000 description 1
230000030279 gene silencing Effects 0.000 description 1
230000004077 genetic alteration Effects 0.000 description 1
231100000118 genetic alteration Toxicity 0.000 description 1
102000054766 genetic haplotypes Human genes 0.000 description 1
210000004602 germ cell Anatomy 0.000 description 1
239000011521 glass Substances 0.000 description 1
125000000291 glutamic acid group Chemical group N[C@@H](CCC(O)=O)C(=O)* 0.000 description 1
XDDAORKBJWWYJS-UHFFFAOYSA-N glyphosate Chemical compound OC(=O)CNCP(O)(O)=O XDDAORKBJWWYJS-UHFFFAOYSA-N 0.000 description 1
229940097068 glyphosate Drugs 0.000 description 1
238000000227 grinding Methods 0.000 description 1
210000003958 hematopoietic stem cell Anatomy 0.000 description 1
230000002949 hemolytic effect Effects 0.000 description 1
230000002363 herbicidal effect Effects 0.000 description 1
239000004009 herbicide Substances 0.000 description 1
210000001320 hippocampus Anatomy 0.000 description 1
238000000265 homogenisation Methods 0.000 description 1
102000053020 human ApoE Human genes 0.000 description 1
102000052611 human IL6 Human genes 0.000 description 1
208000020346 hyperlipoproteinemia Diseases 0.000 description 1
208000020887 hyperlipoproteinemia type 3 Diseases 0.000 description 1
238000010191 image analysis Methods 0.000 description 1
238000003384 imaging method Methods 0.000 description 1
210000000987 immune system Anatomy 0.000 description 1
239000007943 implant Substances 0.000 description 1
230000002779 inactivation Effects 0.000 description 1
238000010348 incorporation Methods 0.000 description 1
230000004054 inflammatory process Effects 0.000 description 1
230000000977 initiatory effect Effects 0.000 description 1
229960003786 inosine Drugs 0.000 description 1
229940125396 insulin Drugs 0.000 description 1
230000002687 intercalation Effects 0.000 description 1
238000009830 intercalation Methods 0.000 description 1
208000003243 intestinal obstruction Diseases 0.000 description 1
210000000936 intestine Anatomy 0.000 description 1
230000001788 irregular Effects 0.000 description 1
238000002955 isolation Methods 0.000 description 1
210000003292 kidney cell Anatomy 0.000 description 1
229960004194 lidocaine Drugs 0.000 description 1
239000007788 liquid Substances 0.000 description 1
XIXADJRWDQXREU-UHFFFAOYSA-M lithium acetate Chemical compound [Li+].CC([O-])=O XIXADJRWDQXREU-UHFFFAOYSA-M 0.000 description 1
210000005229 liver cell Anatomy 0.000 description 1
230000007774 longterm Effects 0.000 description 1
201000005202 lung cancer Diseases 0.000 description 1
108010056929 lyticase Proteins 0.000 description 1
229910001629 magnesium chloride Inorganic materials 0.000 description 1
238000009115 maintenance therapy Methods 0.000 description 1
235000009973 maize Nutrition 0.000 description 1
201000003175 male breast cancer Diseases 0.000 description 1
208000010907 male breast carcinoma Diseases 0.000 description 1
239000003550 marker Substances 0.000 description 1
239000000463 material Substances 0.000 description 1
238000005259 measurement Methods 0.000 description 1
MIKKOBKEXMRYFQ-WZTVWXICSA-N meglumine amidotrizoate Chemical compound C[NH2+]C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.CC(=O)NC1=C(I)C(NC(C)=O)=C(I)C(C([O-])=O)=C1I MIKKOBKEXMRYFQ-WZTVWXICSA-N 0.000 description 1
208000022499 mismatch repair cancer syndrome Diseases 0.000 description 1
238000012544 monitoring process Methods 0.000 description 1
239000004570 mortar (masonry) Substances 0.000 description 1
210000003097 mucus Anatomy 0.000 description 1
101150049514 mutL gene Proteins 0.000 description 1
AYOOGWWGECJQPI-NSHDSACASA-N n-[(1s)-1-(5-fluoropyrimidin-2-yl)ethyl]-3-(3-propan-2-yloxy-1h-pyrazol-5-yl)imidazo[4,5-b]pyridin-5-amine Chemical compound N1C(OC(C)C)=CC(N2C3=NC(N[C@@H](C)C=4N=CC(F)=CN=4)=CC=C3N=C2)=N1 AYOOGWWGECJQPI-NSHDSACASA-N 0.000 description 1
POFWRMVFWIJXHP-UHFFFAOYSA-N n-benzyl-9-(oxan-2-yl)purin-6-amine Chemical compound C=1C=CC=CC=1CNC(C=1N=C2)=NC=NC=1N2C1CCCCO1 POFWRMVFWIJXHP-UHFFFAOYSA-N 0.000 description 1
230000009826 neoplastic cell growth Effects 0.000 description 1
210000002682 neurofibrillary tangle Anatomy 0.000 description 1
210000002569 neuron Anatomy 0.000 description 1
210000003924 normoblast Anatomy 0.000 description 1
239000002773 nucleotide Substances 0.000 description 1
230000030648 nucleus localization Effects 0.000 description 1
210000000056 organ Anatomy 0.000 description 1
210000004789 organ system Anatomy 0.000 description 1
201000008968 osteosarcoma Diseases 0.000 description 1
230000002018 overexpression Effects 0.000 description 1
108700042657 p16 Genes Proteins 0.000 description 1
230000007170 pathology Effects 0.000 description 1
210000005259 peripheral blood Anatomy 0.000 description 1
239000011886 peripheral blood Substances 0.000 description 1
230000002085 persistent effect Effects 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
208000028591 pheochromocytoma Diseases 0.000 description 1
150000008300 phosphoramidites Chemical class 0.000 description 1
239000000419 plant extract Substances 0.000 description 1
239000013600 plasmid vector Substances 0.000 description 1
208000015768 polyposis Diseases 0.000 description 1
239000011148 porous material Substances 0.000 description 1
239000002243 precursor Substances 0.000 description 1
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
108090000765 processed proteins & peptides Proteins 0.000 description 1
230000002250 progressing effect Effects 0.000 description 1
230000000750 progressive effect Effects 0.000 description 1
230000001737 promoting effect Effects 0.000 description 1
210000002307 prostate Anatomy 0.000 description 1
230000004952 protein activity Effects 0.000 description 1
230000004853 protein function Effects 0.000 description 1
XNSAINXGIQZQOO-SRVKXCTJSA-N protirelin Chemical compound NC(=O)[C@@H]1CCCN1C(=O)[C@@H](NC(=O)[C@H]1NC(=O)CC1)CC1=CN=CN1 XNSAINXGIQZQOO-SRVKXCTJSA-N 0.000 description 1
230000005180 public health Effects 0.000 description 1
239000005297 pyrex Substances 0.000 description 1
MUPFEKGTMRGPLJ-ZQSKZDJDSA-N raffinose 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[C@@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O2)O)O1 MUPFEKGTMRGPLJ-ZQSKZDJDSA-N 0.000 description 1
230000008707 rearrangement Effects 0.000 description 1
101150079601 recA gene Proteins 0.000 description 1
102000005962 receptors Human genes 0.000 description 1
108020003175 receptors Proteins 0.000 description 1
238000011084 recovery Methods 0.000 description 1
210000000664 rectum Anatomy 0.000 description 1
230000001105 regulatory effect Effects 0.000 description 1
238000009256 replacement therapy Methods 0.000 description 1
230000002207 retinal effect Effects 0.000 description 1
108010056030 retronectin Proteins 0.000 description 1
230000001177 retroviral effect Effects 0.000 description 1
238000012552 review Methods 0.000 description 1
229920002477 rna polymer Polymers 0.000 description 1
102200017779 rs10132601 Human genes 0.000 description 1
102200056704 rs1048661 Human genes 0.000 description 1
102200029567 rs104893723 Human genes 0.000 description 1
102220316675 rs104893831 Human genes 0.000 description 1
102200047331 rs104894010 Human genes 0.000 description 1
102200121670 rs104894031 Human genes 0.000 description 1
102200005748 rs104894094 Human genes 0.000 description 1
102200006423 rs104894097 Human genes 0.000 description 1
102200005779 rs104894098 Human genes 0.000 description 1
102200006384 rs104894099 Human genes 0.000 description 1
102200070532 rs104894304 Human genes 0.000 description 1
102200007372 rs104894359 Human genes 0.000 description 1
102200145342 rs104894410 Human genes 0.000 description 1
102200110327 rs104894510 Human genes 0.000 description 1
102200132360 rs104894548 Human genes 0.000 description 1
102200076370 rs104894837 Human genes 0.000 description 1
102200009644 rs104895218 Human genes 0.000 description 1
102220193096 rs1057516044 Human genes 0.000 description 1
102220195630 rs1057518550 Human genes 0.000 description 1
102220197458 rs1057519447 Human genes 0.000 description 1
102200131949 rs1057519639 Human genes 0.000 description 1
102220197702 rs1057519652 Human genes 0.000 description 1
102220210465 rs1057524438 Human genes 0.000 description 1
102200106727 rs1060501203 Human genes 0.000 description 1
102200006121 rs1060501260 Human genes 0.000 description 1
102220214551 rs1060502911 Human genes 0.000 description 1
102220279101 rs1060504184 Human genes 0.000 description 1
102220088315 rs1064792864 Human genes 0.000 description 1
102220225381 rs1064794269 Human genes 0.000 description 1
102200006421 rs1064794292 Human genes 0.000 description 1
102200148409 rs1064795534 Human genes 0.000 description 1
102220232206 rs1085307205 Human genes 0.000 description 1
102220232290 rs1085307290 Human genes 0.000 description 1
102220014003 rs111033222 Human genes 0.000 description 1
102200074797 rs111033564 Human genes 0.000 description 1
102220236881 rs1135401945 Human genes 0.000 description 1
102220069578 rs114982090 Human genes 0.000 description 1
102200128619 rs115545701 Human genes 0.000 description 1
102200050481 rs11567735 Human genes 0.000 description 1
102220322900 rs1177143902 Human genes 0.000 description 1
102200136022 rs11789099 Human genes 0.000 description 1
102200089285 rs120074125 Human genes 0.000 description 1
102220283107 rs1218848193 Human genes 0.000 description 1
102200037667 rs121908026 Human genes 0.000 description 1
102200039197 rs121908520 Human genes 0.000 description 1
102200128615 rs121908750 Human genes 0.000 description 1
102200128186 rs121908752 Human genes 0.000 description 1
102200128187 rs121908802 Human genes 0.000 description 1
102200128188 rs121908803 Human genes 0.000 description 1
102200054573 rs121908990 Human genes 0.000 description 1
102200128585 rs121909031 Human genes 0.000 description 1
102200076819 rs121913517 Human genes 0.000 description 1
102200006537 rs121913529 Human genes 0.000 description 1
102200006540 rs121913530 Human genes 0.000 description 1
102200017268 rs121918392 Human genes 0.000 description 1
102220280130 rs1226604148 Human genes 0.000 description 1
102220277084 rs1322095633 Human genes 0.000 description 1
102200024624 rs132630284 Human genes 0.000 description 1
102220262831 rs1326865470 Human genes 0.000 description 1
102220286190 rs1342218617 Human genes 0.000 description 1
102200121863 rs137852744 Human genes 0.000 description 1
102200124775 rs137853292 Human genes 0.000 description 1
102200161970 rs137853294 Human genes 0.000 description 1
102200161982 rs137853296 Human genes 0.000 description 1
102220034184 rs137853920 Human genes 0.000 description 1
102220229235 rs138190453 Human genes 0.000 description 1
102200128583 rs140502196 Human genes 0.000 description 1
102220270116 rs1415605220 Human genes 0.000 description 1
102220257442 rs1445690889 Human genes 0.000 description 1
102200151111 rs146350208 Human genes 0.000 description 1
102220191062 rs149483341 Human genes 0.000 description 1
102220121381 rs150418024 Human genes 0.000 description 1
102220020371 rs151020603 Human genes 0.000 description 1
102220254005 rs1553303351 Human genes 0.000 description 1
102220285296 rs1553367602 Human genes 0.000 description 1
102220277218 rs1553410216 Human genes 0.000 description 1
102220335359 rs1553410255 Human genes 0.000 description 1
102200089630 rs1553619440 Human genes 0.000 description 1
102220258448 rs1553630426 Human genes 0.000 description 1
102200072476 rs1553721236 Human genes 0.000 description 1
102220278428 rs1553997347 Human genes 0.000 description 1
102220277689 rs1554067127 Human genes 0.000 description 1
102220263006 rs1554248797 Human genes 0.000 description 1
102200116824 rs1554263326 Human genes 0.000 description 1
102200005782 rs1554653960 Human genes 0.000 description 1
102200005751 rs1554654024 Human genes 0.000 description 1
102220279096 rs1554888137 Human genes 0.000 description 1
102220342158 rs1555419932 Human genes 0.000 description 1
102220246653 rs1555487316 Human genes 0.000 description 1
102220287708 rs1555515611 Human genes 0.000 description 1
102220328559 rs1555607779 Human genes 0.000 description 1
102220282941 rs1555609193 Human genes 0.000 description 1
102200064260 rs1555729468 Human genes 0.000 description 1
102220284481 rs1555853970 Human genes 0.000 description 1
102220330627 rs1555858729 Human genes 0.000 description 1
102200126997 rs17081389 Human genes 0.000 description 1
102200025794 rs179363887 Human genes 0.000 description 1
102220020489 rs1800076 Human genes 0.000 description 1
102200131747 rs1800557 Human genes 0.000 description 1
102220036089 rs180177094 Human genes 0.000 description 1
102200038843 rs199472766 Human genes 0.000 description 1
102200108802 rs199473082 Human genes 0.000 description 1
102200096983 rs199473504 Human genes 0.000 description 1
102200077351 rs200180113 Human genes 0.000 description 1
102200085125 rs200378205 Human genes 0.000 description 1
102220198852 rs200818252 Human genes 0.000 description 1
102220128858 rs200860772 Human genes 0.000 description 1
102220080355 rs201474883 Human genes 0.000 description 1
102200128587 rs201958172 Human genes 0.000 description 1
102220010535 rs202009639 Human genes 0.000 description 1
102220067588 rs202162520 Human genes 0.000 description 1
102200077477 rs267607103 Human genes 0.000 description 1
102200076422 rs267607500 Human genes 0.000 description 1
102200067541 rs281864846 Human genes 0.000 description 1
102200124874 rs28928896 Human genes 0.000 description 1
102200090055 rs28933082 Human genes 0.000 description 1
102200009101 rs28934568 Human genes 0.000 description 1
102200022338 rs28936703 Human genes 0.000 description 1
102200058025 rs28941782 Human genes 0.000 description 1
102200124965 rs3092902 Human genes 0.000 description 1
102200082891 rs334 Human genes 0.000 description 1
102200082894 rs334 Human genes 0.000 description 1
102200082941 rs33915112 Human genes 0.000 description 1
102220005317 rs33915112 Human genes 0.000 description 1
102200117901 rs33927093 Human genes 0.000 description 1
102200082892 rs33930165 Human genes 0.000 description 1
102200082878 rs33935445 Human genes 0.000 description 1
102200082936 rs33950507 Human genes 0.000 description 1
102200158841 rs33965337 Human genes 0.000 description 1
102220005461 rs33991910 Human genes 0.000 description 1
102200082909 rs34387455 Human genes 0.000 description 1
102200123056 rs34693334 Human genes 0.000 description 1
102200113754 rs34993780 Human genes 0.000 description 1
102200118260 rs35278874 Human genes 0.000 description 1
102200117931 rs35849199 Human genes 0.000 description 1
102200014686 rs367543072 Human genes 0.000 description 1
102200128612 rs368505753 Human genes 0.000 description 1
102200006383 rs372266620 Human genes 0.000 description 1
102220271952 rs372987093 Human genes 0.000 description 1
102220101362 rs377289804 Human genes 0.000 description 1
102220102934 rs377580634 Human genes 0.000 description 1
102220003661 rs387906443 Human genes 0.000 description 1
102220003662 rs387906444 Human genes 0.000 description 1
102220003786 rs387906474 Human genes 0.000 description 1
102220020411 rs397508256 Human genes 0.000 description 1
102200128611 rs397508272 Human genes 0.000 description 1
102220020429 rs397508285 Human genes 0.000 description 1
102200128618 rs397508403 Human genes 0.000 description 1
102220020523 rs397508412 Human genes 0.000 description 1
102200128586 rs397508464 Human genes 0.000 description 1
102220020648 rs397508571 Human genes 0.000 description 1
102220020679 rs397508609 Human genes 0.000 description 1
102200128592 rs397508718 Human genes 0.000 description 1
102220020780 rs397508738 Human genes 0.000 description 1
102200128189 rs397508765 Human genes 0.000 description 1
102200128184 rs397508780 Human genes 0.000 description 1
102200128185 rs397508783 Human genes 0.000 description 1
102220020826 rs397508788 Human genes 0.000 description 1
102220028975 rs398123345 Human genes 0.000 description 1
102220029458 rs398123550 Human genes 0.000 description 1
102220005366 rs41328049 Human genes 0.000 description 1
102200089631 rs5030808 Human genes 0.000 description 1
102220036087 rs515726127 Human genes 0.000 description 1
102220194811 rs550945533 Human genes 0.000 description 1
102220282626 rs55816927 Human genes 0.000 description 1
102200006128 rs559848002 Human genes 0.000 description 1
102200049186 rs565090080 Human genes 0.000 description 1
102220070377 rs570770626 Human genes 0.000 description 1
102220059910 rs587778189 Human genes 0.000 description 1
102220065608 rs587779008 Human genes 0.000 description 1
102200108474 rs587780068 Human genes 0.000 description 1
102220046765 rs61748401 Human genes 0.000 description 1
102200047033 rs61752158 Human genes 0.000 description 1
102200028555 rs61754448 Human genes 0.000 description 1
102220034824 rs62507326 Human genes 0.000 description 1
102200113676 rs62625011 Human genes 0.000 description 1
102220033067 rs62645939 Human genes 0.000 description 1
102200061269 rs63749851 Human genes 0.000 description 1
102200061598 rs63749880 Human genes 0.000 description 1
102200061590 rs63749885 Human genes 0.000 description 1
102200061486 rs63749925 Human genes 0.000 description 1
102200058106 rs63749967 Human genes 0.000 description 1
102200061468 rs63750227 Human genes 0.000 description 1
102200058165 rs63750306 Human genes 0.000 description 1
102200058168 rs63750306 Human genes 0.000 description 1
102200058147 rs63750353 Human genes 0.000 description 1
102200061376 rs63750378 Human genes 0.000 description 1
102200027365 rs63750381 Human genes 0.000 description 1
102200061543 rs63750543 Human genes 0.000 description 1
102200058131 rs63750601 Human genes 0.000 description 1
102200163543 rs63750656 Human genes 0.000 description 1
102200027366 rs63750732 Human genes 0.000 description 1
102200058143 rs63750800 Human genes 0.000 description 1
102200164339 rs63750952 Human genes 0.000 description 1
102200061535 rs63751019 Human genes 0.000 description 1
102200058151 rs63751037 Human genes 0.000 description 1
102200061493 rs63751223 Human genes 0.000 description 1
102200061551 rs63751235 Human genes 0.000 description 1
102200061470 rs63751416 Human genes 0.000 description 1
102200113714 rs72551351 Human genes 0.000 description 1
102200113705 rs72551353 Human genes 0.000 description 1
102200006618 rs727503094 Human genes 0.000 description 1
102220052411 rs727503384 Human genes 0.000 description 1
102220056582 rs730881193 Human genes 0.000 description 1
102200104839 rs730882008 Human genes 0.000 description 1
102220010989 rs745497215 Human genes 0.000 description 1
102200006406 rs746834149 Human genes 0.000 description 1
102220251321 rs747995722 Human genes 0.000 description 1
102220093316 rs749037674 Human genes 0.000 description 1
102220094427 rs749037674 Human genes 0.000 description 1
102220319451 rs749383450 Human genes 0.000 description 1
102200006187 rs749714198 Human genes 0.000 description 1
102200085130 rs749893889 Human genes 0.000 description 1
102220217906 rs752014453 Human genes 0.000 description 1
102220263809 rs752014453 Human genes 0.000 description 1
102200005763 rs754806883 Human genes 0.000 description 1
102220089225 rs757186755 Human genes 0.000 description 1
102200128617 rs75961395 Human genes 0.000 description 1
102220097789 rs759728549 Human genes 0.000 description 1
102200128597 rs76371115 Human genes 0.000 description 1
102220222423 rs765125459 Human genes 0.000 description 1
102220089625 rs767713084 Human genes 0.000 description 1
102200047118 rs769268803 Human genes 0.000 description 1
102220058951 rs773301485 Human genes 0.000 description 1
102200043546 rs773774134 Human genes 0.000 description 1
102220244682 rs778284147 Human genes 0.000 description 1
102200128590 rs77834169 Human genes 0.000 description 1
102220218940 rs781647403 Human genes 0.000 description 1
102220128445 rs782614415 Human genes 0.000 description 1
102220059996 rs786201758 Human genes 0.000 description 1
102220060489 rs786201891 Human genes 0.000 description 1
102200102859 rs786202962 Human genes 0.000 description 1
102200102871 rs786202962 Human genes 0.000 description 1
102220059788 rs786203019 Human genes 0.000 description 1
102220322728 rs786204928 Human genes 0.000 description 1
102220063596 rs786205046 Human genes 0.000 description 1
102200128588 rs78655421 Human genes 0.000 description 1
102200128589 rs78655421 Human genes 0.000 description 1
102200128591 rs78655421 Human genes 0.000 description 1
102200009422 rs78846775 Human genes 0.000 description 1
102220075173 rs796052258 Human genes 0.000 description 1
102220067340 rs797044672 Human genes 0.000 description 1
102200145545 rs80338859 Human genes 0.000 description 1
102220021919 rs80356897 Human genes 0.000 description 1
102220020985 rs80357073 Human genes 0.000 description 1
102200067509 rs80358507 Human genes 0.000 description 1
102220019386 rs80358780 Human genes 0.000 description 1
102220080895 rs863223425 Human genes 0.000 description 1
102200031406 rs864309483 Human genes 0.000 description 1
102220262942 rs869312802 Human genes 0.000 description 1
102220244699 rs875989900 Human genes 0.000 description 1
102200016026 rs876658156 Human genes 0.000 description 1
102200006185 rs878853646 Human genes 0.000 description 1
102200006186 rs878853647 Human genes 0.000 description 1
102200006426 rs878853650 Human genes 0.000 description 1
102220238659 rs879254257 Human genes 0.000 description 1
102220105351 rs879254456 Human genes 0.000 description 1
102220105352 rs879254457 Human genes 0.000 description 1
102220105636 rs879254679 Human genes 0.000 description 1
102220197727 rs879254749 Human genes 0.000 description 1
102220105770 rs879254783 Human genes 0.000 description 1
102200038269 rs879254891 Human genes 0.000 description 1
102220107183 rs886037729 Human genes 0.000 description 1
102220123883 rs886043541 Human genes 0.000 description 1
102220153278 rs886060980 Human genes 0.000 description 1
102220147913 rs886061132 Human genes 0.000 description 1
102220202426 rs893389047 Human genes 0.000 description 1
229940081969 saccharomyces cerevisiae Drugs 0.000 description 1
150000003839 salts Chemical class 0.000 description 1
201000000980 schizophrenia Diseases 0.000 description 1
230000007017 scission Effects 0.000 description 1
238000012216 screening Methods 0.000 description 1
230000003248 secreting effect Effects 0.000 description 1
210000002955 secretory cell Anatomy 0.000 description 1
230000035945 sensitivity Effects 0.000 description 1
239000013605 shuttle vector Substances 0.000 description 1
238000002741 site-directed mutagenesis Methods 0.000 description 1
210000003491 skin Anatomy 0.000 description 1
210000001626 skin fibroblast Anatomy 0.000 description 1
239000007787 solid Substances 0.000 description 1
239000002904 solvent Substances 0.000 description 1
238000000638 solvent extraction Methods 0.000 description 1
229940063673 spermidine Drugs 0.000 description 1
125000001424 substituent group Chemical group 0.000 description 1
230000001629 suppression Effects 0.000 description 1
239000000725 suspension Substances 0.000 description 1
230000002459 sustained effect Effects 0.000 description 1
210000000106 sweat gland Anatomy 0.000 description 1
108091035539 telomere Proteins 0.000 description 1
102000055501 telomere Human genes 0.000 description 1
210000003411 telomere Anatomy 0.000 description 1
238000011191 terminal modification Methods 0.000 description 1
208000035203 thalassemia minor Diseases 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
238000011285 therapeutic regimen Methods 0.000 description 1
201000002510 thyroid cancer Diseases 0.000 description 1
231100000331 toxic Toxicity 0.000 description 1
230000002588 toxic effect Effects 0.000 description 1
231100000419 toxicity Toxicity 0.000 description 1
230000001988 toxicity Effects 0.000 description 1
238000013518 transcription Methods 0.000 description 1
230000035897 transcription Effects 0.000 description 1
230000001131 transforming effect Effects 0.000 description 1
QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
230000005740 tumor formation Effects 0.000 description 1
230000007306 turnover Effects 0.000 description 1
229940035893 uracil Drugs 0.000 description 1
210000003932 urinary bladder Anatomy 0.000 description 1
208000012991 uterine carcinoma Diseases 0.000 description 1
239000003981 vehicle Substances 0.000 description 1
108700026220 vif Genes Proteins 0.000 description 1
229960005080 warfarin Drugs 0.000 description 1
PJVWKTKQMONHTI-UHFFFAOYSA-N warfarin Chemical compound OC=1C2=CC=CC=C2OC(=O)C=1C(CC(=O)C)C1=CC=CC=C1 PJVWKTKQMONHTI-UHFFFAOYSA-N 0.000 description 1
208000009825 warfarin sensitivity Diseases 0.000 description 1
239000008215 water for injection Substances 0.000 description 1
230000004580 weight loss Effects 0.000 description 1
239000007222 ypd medium Substances 0.000 description 1

Classifications

- 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
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
- 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
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/06—Antianaemics
- 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
- C12N15/10—Processes for the isolation, preparation or purification of DNA or RNA
- C12N15/102—Mutagenizing nucleic acids
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
- 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
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/31—Chemical structure of the backbone
- C12N2310/315—Phosphorothioates
- 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
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/32—Chemical structure of the sugar
- C12N2310/321—2'-O-R Modification
- 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
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/32—Chemical structure of the sugar
- C12N2310/323—Chemical structure of the sugar modified ring structure
- C12N2310/3231—Chemical structure of the sugar modified ring structure having an additional ring, e.g. LNA, ENA
- 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
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/34—Spatial arrangement of the modifications
- C12N2310/346—Spatial arrangement of the modifications having a combination of backbone and sugar modifications

Landscapes

Health & Medical Sciences (AREA)
Engineering & Computer Science (AREA)
Life Sciences & Earth Sciences (AREA)
Chemical & Material Sciences (AREA)
Genetics & Genomics (AREA)
Bioinformatics & Cheminformatics (AREA)
Organic Chemistry (AREA)
Biomedical Technology (AREA)
General Health & Medical Sciences (AREA)
Zoology (AREA)
Biotechnology (AREA)
General Engineering & Computer Science (AREA)
Wood Science & Technology (AREA)
Molecular Biology (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Medicinal Chemistry (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Biochemistry (AREA)
Microbiology (AREA)
Plant Pathology (AREA)
Physics & Mathematics (AREA)
Biophysics (AREA)
Hematology (AREA)
Diabetes (AREA)
Neurosurgery (AREA)
Neurology (AREA)
Crystallography & Structural Chemistry (AREA)
Psychiatry (AREA)
Obesity (AREA)
Gastroenterology & Hepatology (AREA)
Hospice & Palliative Care (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Micro-Organisms Or Cultivation Processes Thereof (AREA)

OA1200200302A 2000-03-27 2001-03-27 Targeted chromosomal genomic alterations with modified single stranded oligonucleotides. OA12240A (en)

Applications Claiming Priority (4)

Application Number	Priority Date	Filing Date
US19217600P	2000-03-27	2000-03-27
US19217900P	2000-03-27	2000-03-27
US20853800P	2000-06-01	2000-06-01
US24498900P	2000-10-30	2000-10-30

Publications (1)

Publication Number	Publication Date
OA12240A true OA12240A (en)	2006-05-10

Family

ID=27497924

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
OA1200200302A OA12240A (en)	2000-03-27	2001-03-27	Targeted chromosomal genomic alterations with modified single stranded oligonucleotides.

Country Status (12)

Country	Link
US (1)	US7226785B2 (fr)
EP (1)	EP1268768A2 (fr)
JP (1)	JP2003528607A (fr)
KR (1)	KR20030003240A (fr)
AP (1)	AP2002002638A0 (fr)
AU (1)	AU4948801A (fr)
CA (1)	CA2404780A1 (fr)
IL (2)	IL151948A0 (fr)
MX (1)	MXPA02009627A (fr)
NZ (1)	NZ521698A (fr)
OA (1)	OA12240A (fr)
WO (1)	WO2001073002A2 (fr)

Families Citing this family (83)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US6936467B2 (en) *	2000-03-27	2005-08-30	University Of Delaware	Targeted chromosomal genomic alterations with modified single stranded oligonucleotides
AU2001263271A1 (en) *	2000-05-17	2001-11-26	University Of Delaware	Plant gene targeting using oligonucleotides
EP1414840A4 (fr)	2001-03-27	2005-04-13	Univ Delaware	Applications genomiques destinees a des oligonucleotides modifies
US7468244B2 (en)	2001-09-27	2008-12-23	University Of Delaware	Polymorphism detection and separation
EP1446503A2 (fr)	2001-09-27	2004-08-18	University Of Delaware	Composition et procedes facilitant les modifications de sequences d'acide nucleique dirigees par des oligonucleotides
WO2003075856A2 (fr)	2002-03-07	2003-09-18	University Of Delaware	Methodes, compositions et kits visant a ameliorer l'alteration de sequences d'acides nucleiques a l'aide d'oligonucleotides grace a des compositions contenant un inhibiteur d'histone deacetylase, une beta proteine du phage lambda, ou de l'hydroxyuree
ITMI20030434A1 (it)	2003-03-07	2004-09-08	Istituto Oncologico Romagnolo Coope Rativa Sociale	Metodo per l'individuazione di tumori del colon-retto.
DE10345021A1 (de) *	2003-09-23	2005-05-04	Univ Potsdam	Verfahren zur nichtinvasiven Früherkennung von Dickdarmkrebs und/oder Darmkrebsvorläuferzellen
US7480382B2 (en) *	2003-09-30	2009-01-20	Microsoft Corporation	Image file container
WO2005094370A2 (fr)	2004-03-29	2005-10-13	The General Hospital Corporation	Compositions de complexe d'oligonucleotides et procedes d'utilisation de celles-ci comme outils de modification de genes
WO2007073149A1 (fr)	2005-12-22	2007-06-28	Keygene N.V.	Variantes de nucleotides ameliorant les echanges de nucleotides cibles
JP5713377B2 (ja)	2005-12-28	2015-05-07	ザスクリプスリサーチインスティテュート	薬物標的としての天然アンチセンスおよび非コードｒｎａ転写物
US8999634B2 (en)	2007-04-27	2015-04-07	Quest Diagnostics Investments Incorporated	Nucleic acid detection combining amplification with fragmentation
EP2167660A1 (fr) *	2007-06-22	2010-03-31	Keygene N.V.	Échange nucléotidique ciblé avec des oligonucléotides modifiés améliorés
KR20140050759A (ko)	2007-12-21	2014-04-29	키진 엔.브이.	식물 원형질체 내로 폴리에틸렌 글리콜 매개 돌연변이 뉴클레오염기의 도입을 이용한 개선된 돌연변이 생성방법
AU2009292297B2 (en)	2008-09-11	2014-03-06	Keygene N.V.	Method for diagnostic marker development
CN102239260B (zh) *	2008-10-03	2017-04-12	库尔纳公司	通过抑制针对载脂蛋白‑a1的天然反义转录物治疗载脂蛋白‑a1相关疾病
ES2600781T3 (es)	2008-12-04	2017-02-10	Curna, Inc.	Tratamiento para enfermedades relacionadas con el factor de crecimiento del endotelio vascular (vegf) mediante la inhibición de transcritos antisentido naturales de vegf
ES2629630T3 (es)	2008-12-04	2017-08-11	Curna, Inc.	Tratamiento de enfermedades relacionadas con eritropoyetina (EPO) mediante inhibición del transcrito antisentido natural a EPO
US20110294870A1 (en)	2008-12-04	2011-12-01	Opko Curna, Llc	Treatment of tumor suppressor gene related diseases by inhibition of natural antisense transcript to the gene
US20110312094A1 (en)	2008-12-22	2011-12-22	Keygene N.V.	Use of double stranded rna to increase the efficiency of targeted gene alteration in plant protoplasts
ES2762610T3 (es)	2009-02-12	2020-05-25	Curna Inc	Tratamiento de enfermedades relacionadas con el factor neurotrófico derivado de cerebro (BDNF) por inhibición de transcrito antisentido natural para BDNF
CN102482677B (zh)	2009-03-16	2017-10-17	库尔纳公司	通过抑制nrf2的天然反义转录物治疗核因子(红细胞衍生2)‑样2(nrf2)相关疾病
WO2010107740A2 (fr)	2009-03-17	2010-09-23	Curna, Inc.	Traitement des maladies associées à l'homologue du delta-like 1 (dlk1) par inhibition du transcrit antisens naturel de dlk1
ES2609655T3 (es)	2009-05-06	2017-04-21	Curna, Inc.	Tratamiento de enfermedades relacionadas con tristetraprolina (TTP) mediante inhibición de transcrito antisentido natural para TTP
CN103223177B (zh)	2009-05-06	2016-08-10	库尔纳公司	通过针对脂质转运和代谢基因的天然反义转录物的抑制治疗脂质转运和代谢基因相关疾病
JP5931720B2 (ja)	2009-05-08	2016-06-08	クルナ・インコーポレーテッド	Ｄｍｄファミリーに対する天然アンチセンス転写物の抑制によるジストロフィンファミリー関連疾患の治療
DK2432881T3 (en)	2009-05-18	2018-02-26	Curna Inc	TREATMENT OF REPROGRAMMING FACTOR-RELATED DISEASES BY INHIBITING NATURAL ANTISENSE TRANSCRIPTS TO A REPROGRAMMING FACTOR
CA2762987A1 (fr)	2009-05-22	2010-11-25	Joseph Collard	Traitement des maladies liees au facteur de transcription e3 (tfe3) et au substrat recepteur d'insuline 2 (irs2) par inhibition du transcript antisens naturel du tfe3
KR101704988B1 (ko)	2009-05-28	2017-02-08	큐알엔에이, 인크.	항바이러스 유전자에 대한 천연 안티센스 전사체의 억제에 의한 항바이러스 유전자 관련된 질환의 치료
US8951981B2 (en)	2009-06-16	2015-02-10	Curna, Inc.	Treatment of paraoxonase 1 (PON1) related diseases by inhibition of natural antisense transcript to PON1
WO2010148050A2 (fr)	2009-06-16	2010-12-23	Curna, Inc.	Traitement de maladies liées au gène du collagène par inhibition d'un produit de transcription antisens naturel à un gène du collagène
WO2010151671A2 (fr)	2009-06-24	2010-12-29	Curna, Inc.	Traitement de maladies associées au récepteur de facteur nécrosant des tumeurs 2 (tnfr2) par inhibition de la transcription antisens naturelle de tnfr2
EP2446037B1 (fr)	2009-06-26	2016-04-20	CuRNA, Inc.	Traitement de maladies associées aux gènes liés au syndrome de down par inhibition des gènes liés au syndrome de down médiée par le produit de transcription antisens naturel
CN102712925B (zh)	2009-07-24	2017-10-27	库尔纳公司	通过抑制sirtuin(sirt)的天然反义转录物来治疗sirtuin(sirt)相关性疾病
CN102762731B (zh)	2009-08-05	2018-06-22	库尔纳公司	通过抑制针对胰岛素基因(ins)的天然反义转录物来治疗胰岛素基因(ins)相关的疾病
CN104313027B (zh)	2009-08-11	2018-11-20	库尔纳公司	通过抑制脂连蛋白(adipoq)的天然反义转录物治疗脂连蛋白(adipoq)相关疾病
KR101805213B1 (ko)	2009-08-21	2017-12-06	큐알엔에이, 인크.	Ｃｈｉｐ에 대한 천연 안티센스 전사체의 억제에 의한 “ｈｓｐ70-상호작용 단백질(ｃｈｉｐ)의 ｃ-말단” 관련된 질환의 치료
CA2771172C (fr)	2009-08-25	2021-11-30	Opko Curna, Llc	Traitement de maladies associees a la proteine d'activation de gtpase contenant un motif iq (iqgap), par inhibition d'un transcrit antisens naturel de iqgap
US20120295952A1 (en)	2009-09-25	2012-11-22	Curna, Inc.	Treatment of filaggrin (flg) related diseases by modulation of flg expression and activity
WO2011058555A1 (fr)	2009-11-12	2011-05-19	Yeda Research And Development Co. Ltd.	Procédé d'édition de l'adn dans une cellule et constructions ayant cette capacité
JP6025567B2 (ja)	2009-12-16	2016-11-16	カッパーアールエヌエー，インコーポレイテッド	膜結合転写因子ペプチダーゼ、部位１（ｍｂｔｐｓ１）に対する天然アンチセンス転写物の阻害によるｍｂｔｐｓ１関連性疾患の治療
CN102869776B (zh)	2009-12-23	2017-06-23	库尔纳公司	通过抑制肝细胞生长因子(hgf)的天然反义转录物而治疗hgf相关疾病
RU2619185C2 (ru)	2009-12-23	2017-05-12	Курна, Инк.	Лечение заболеваний, связанных с разобщающим белком 2 (ucp2), путем ингибирования природного антисмыслового транскрипта к ucp2
EP2519633B1 (fr)	2009-12-29	2017-10-25	CuRNA, Inc.	Traitement de maladies liées au facteur respiratoire nucléaire 1 (nrf1) par l'inhibition du produit de transcription antisens naturel de nrf1
ES2585829T3 (es)	2009-12-29	2016-10-10	Curna, Inc.	Tratamiento de las enfermedades relacionadas con la proteína tumoral 63 (p63) por inhibición de transcripción antisentido natural a p63
CA2785727C (fr)	2009-12-31	2020-01-07	Curna, Inc.	Traitement de maladies liees au substrat 2 du recepteur de l'insuline (irs2) par inhibition du produit de transcription antisens naturel d'irs2 et du facteur de transcription e3 (tfe3)
CA2785832A1 (fr)	2010-01-04	2011-07-07	Curna, Inc.	Traitement de maladies liees au facteur de regulation de l'interferon 8 (irf8) par l'inhibition du produit de transcription antisens naturel de l'irf8
KR101853509B1 (ko)	2010-01-06	2018-04-30	큐알엔에이, 인크.	췌장 발달 유전자에 대한 천연 안티센스 전사체의 억제에 의한 췌장 발달 유전자와 관련된 질환의 치료
JP6027893B2 (ja)	2010-01-11	2016-11-16	カッパーアールエヌエー，インコーポレイテッド	性ホルモン結合グロブリン（ｓｈｂｇ）に対する天然アンチセンス転写物の阻害による性ホルモン結合グロブリン（ｓｈｂｇ）関連疾患の治療
EP2529015B1 (fr)	2010-01-25	2017-11-15	CuRNA, Inc.	Traitement de maladies liées à la rnase h1 par l'inhibition du produit de transcription naturel antisens de la rnase h1
CN102844435B (zh)	2010-02-22	2017-05-10	库尔纳公司	通过抑制吡咯啉‑5‑羧酸还原酶1(pycr1)的天然反义转录物而治疗pycr1相关疾病
RU2612884C2 (ru)	2010-04-02	2017-03-13	Курна, Инк.	Лечение заболеваний, связанных с колониестимулирующим фактором 3 (csf3), путем ингибирования природного антисмыслового транскрипта k csf3
WO2011127337A2 (fr)	2010-04-09	2011-10-13	Opko Curna Llc	Traitement des maladies associées au facteur de croissance du fibroblaste 21 (fgf21) par l'inhibition d'un produit de la transcription antisens naturel de fgf21
WO2011139387A1 (fr)	2010-05-03	2011-11-10	Opko Curna, Llc	Traitement de maladies liées à une sirtuine (sirt) par inhibition de la transcription antisens naturelle pour donner une sirtuine (sirt)
TWI531370B (zh)	2010-05-14	2016-05-01	可娜公司	藉由抑制ｐａｒ４天然反股轉錄本治療ｐａｒ４相關疾病
US8895528B2 (en)	2010-05-26	2014-11-25	Curna, Inc.	Treatment of atonal homolog 1 (ATOH1) related diseases by inhibition of natural antisense transcript to ATOH1
ES2664585T3 (es)	2010-05-26	2018-04-20	Curna, Inc.	Tratamiento de enfermedades relacionadas con metionina sulfóxido reductasa (MSRA) mediante inhibición del transcrito antisentido natural a MSRA
CN109112126B (zh)	2010-06-23	2024-06-14	库尔纳公司	通过抑制电压门控钠通道α亚基(SCNA)的天然反义转录物而治疗SCNA相关疾病
JP5998131B2 (ja)	2010-07-14	2016-09-28	カッパーアールエヌエー，インコーポレイテッド	Ｄｉｓｃｓｌａｒｇｅｈｏｍｏｌｏｇ（ｄｌｇ）ｄｌｇ１への天然アンチセンス転写物の阻害によるｄｌｇ関連疾患の治療
CN103210086B (zh)	2010-10-06	2017-06-09	库尔纳公司	通过抑制唾液酸酶4(neu4)的天然反义转录物而治疗neu4相关疾病
KR101865433B1 (ko)	2010-10-22	2018-07-13	큐알엔에이, 인크.	알파-l 이두로니다아제 (idua)에 대한 자연 안티센스 전사체의 저해에 의한 idua 관련된 질환의 치료
US10000752B2 (en)	2010-11-18	2018-06-19	Curna, Inc.	Antagonat compositions and methods of use
WO2012071238A2 (fr)	2010-11-23	2012-05-31	Opko Curna Llc	Traitement de maladies associées à nanog par l'inhibition d'un transcript antisens naturel de nanog
DK2646550T3 (en)	2010-12-02	2015-05-26	Keygene Nv	Targeted DNA modification with oligonucleotides
EP2857512B1 (fr)	2010-12-02	2016-06-29	Keygene N.V.	Modification ciblée d'ADN
KR102043422B1 (ko)	2011-06-09	2019-11-11	큐알엔에이, 인크.	프라탁신 (fxn)에 대한 자연 안티센스 전사체의 저해에 의한 프라탁신 (fxn) 관련된 질환의 치료
MX365525B (es)	2011-09-06	2019-06-06	Curna Inc	Compuestos que regulan la expresión de subunidades alfa de canales de sodio regulados por voltaje en enfermedades relacionadas con epilepsia mioclónica severa de la infancia.
HK1210211A1 (en)	2012-03-15	2016-04-15	科纳公司	Treatment of brain derived neurotrophic factor (bdnf) related diseases by inhibition of natural antisense transcript to bdnf
BR112014028631A2 (pt) *	2012-05-16	2017-10-17	Rana Therapeutics Inc	composições e métodos para modulação da expressão da família de genes da hemoglobina
AU2013262699A1 (en)	2012-05-16	2015-01-22	Rana Therapeutics, Inc.	Compositions and methods for modulating ATP2A2 expression
US10837014B2 (en)	2012-05-16	2020-11-17	Translate Bio Ma, Inc.	Compositions and methods for modulating SMN gene family expression
EA201492116A1 (ru)	2012-05-16	2015-05-29	Рана Терапьютикс, Инк.	Композиции и способы для модулирования экспрессии mecp2
SG11201407483YA (en)	2012-05-16	2014-12-30	Rana Therapeutics Inc	Compositions and methods for modulating smn gene family expression
US12359197B2 (en) *	2014-12-12	2025-07-15	Etagen Pharma, Inc.	Compositions and methods for editing nucleic acids in cells utilizing oligonucleotides
WO2016105185A1 (fr)	2014-12-22	2016-06-30	Keygene N.V.	Populations de cals végétaux
US10525076B2 (en)	2015-02-20	2020-01-07	Rosalind Franklin University Of Medicine And Science	Antisense compounds targeting genes associated with cystic fibrosis
EP3259356B1 (fr) *	2015-02-20	2021-12-01	Rosalind Franklin University of Medicine and Science	Composés antisens ciblant des gènes associés à la fibrose kystique
CN107921148A (zh)	2015-05-08	2018-04-17	哈佛学院校长同事会	通用供体干细胞和相关方法
SK500652015A3 (sk) *	2015-10-15	2017-05-03	Ústav Polymérov Sav	Spôsob úpravy funkčného stavu ľubovoľnej mRNA umožňujúci jej selektívne a špecifické rozpoznanie
CA3022319A1 (fr)	2016-05-06	2017-11-09	Tod M. Woolf	Procedes perfectionnes d'edition de genome avec et sans nucleases programmables
WO2019143978A1 (fr)	2018-01-18	2019-07-25	Wisconsin Alumni Research Foundation	Procédé d'atténuation de la voie bêta-amyloïde sur la base de l'édition génique
ES2948817B2 (es) *	2023-03-21	2024-02-21	Univ Madrid Complutense	Modelo animal deficiente en factor v

Family Cites Families (14)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5955363A (en) *	1990-01-03	1999-09-21	Promega Corporation	Vector for in vitro mutagenesis and use thereof
US6136601A (en) *	1991-08-21	2000-10-24	Epoch Pharmaceuticals, Inc.	Targeted mutagenesis in living cells using modified oligonucleotides
US5801154A (en) *	1993-10-18	1998-09-01	Isis Pharmaceuticals, Inc.	Antisense oligonucleotide modulation of multidrug resistance-associated protein
DE733059T1 (de) *	1993-12-09	1997-08-28	Univ Jefferson	Verbindungen und verfahren zur ortsspezifischen mutation in eukaryotischen zellen
US5912340A (en) *	1995-10-04	1999-06-15	Epoch Pharmaceuticals, Inc.	Selective binding complementary oligonucleotides
US5731181A (en) *	1996-06-17	1998-03-24	Thomas Jefferson University	Chimeric mutational vectors having non-natural nucleotides
JP4236812B2 (ja) *	1997-09-12	2009-03-11	エクシコンエ／エス	オリゴヌクレオチド類似体
US6010907A (en) *	1998-05-12	2000-01-04	Kimeragen, Inc.	Eukaryotic use of non-chimeric mutational vectors
US6004804A (en) *	1998-05-12	1999-12-21	Kimeragen, Inc.	Non-chimeric mutational vectors
KR20020013513A (ko)	1999-03-18	2002-02-20	추후제출	Ｘｙｌｏ-ｌｎａ 유사체
US7053207B2 (en)	1999-05-04	2006-05-30	Exiqon A/S	L-ribo-LNA analogues
US6271360B1 (en) *	1999-08-27	2001-08-07	Valigen (Us), Inc.	Single-stranded oligodeoxynucleotide mutational vectors
US6936467B2 (en) *	2000-03-27	2005-08-30	University Of Delaware	Targeted chromosomal genomic alterations with modified single stranded oligonucleotides
US20020119570A1 (en) *	2000-09-25	2002-08-29	Kyonggeun Yoon	Targeted gene correction by single-stranded oligodeoxynucleotides

2001
- 2001-03-27 EP EP01922722A patent/EP1268768A2/fr not_active Withdrawn
- 2001-03-27 JP JP2001570719A patent/JP2003528607A/ja active Pending
- 2001-03-27 AU AU4948801A patent/AU4948801A/xx active Pending
- 2001-03-27 IL IL15194801A patent/IL151948A0/xx unknown
- 2001-03-27 MX MXPA02009627A patent/MXPA02009627A/es not_active Application Discontinuation
- 2001-03-27 WO PCT/US2001/009761 patent/WO2001073002A2/fr not_active Ceased
- 2001-03-27 AP APAP/P/2002/002638A patent/AP2002002638A0/en unknown
- 2001-03-27 KR KR1020027012837A patent/KR20030003240A/ko not_active Ceased
- 2001-03-27 NZ NZ521698A patent/NZ521698A/xx unknown
- 2001-03-27 OA OA1200200302A patent/OA12240A/en unknown
- 2001-03-27 CA CA002404780A patent/CA2404780A1/fr not_active Abandoned
2002
- 2002-09-26 IL IL151948A patent/IL151948A/en not_active IP Right Cessation
- 2002-09-27 US US10/261,185 patent/US7226785B2/en not_active Expired - Lifetime

Also Published As

Publication number	Publication date
AP2002002638A0 (en)	2002-09-30
NZ521698A (en)	2004-08-27
US20040014057A1 (en)	2004-01-22
AU2001249488B2 (en)	2007-02-08
IL151948A0 (en)	2003-04-10
KR20030003240A (ko)	2003-01-09
WO2001073002A2 (fr)	2001-10-04
CA2404780A1 (fr)	2001-10-04
EP1268768A2 (fr)	2003-01-02
AU4948801A (en)	2001-10-08
US7226785B2 (en)	2007-06-05
AU2001249488C1 (en)	2001-10-08
IL151948A (en)	2008-12-29
MXPA02009627A (es)	2004-05-14
WO2001073002A3 (fr)	2002-09-26
JP2003528607A (ja)	2003-09-30

Publication	Publication Date	Title
US7258854B2 (en)	2007-08-21	Targeted chromosomal genomic alterations with modified single stranded oligonucleotides
US7226785B2 (en)	2007-06-05	Targeted chromosomal genomic alterations with modified single stranded oligonucleotides
US20240110179A1 (en)	2024-04-04	Systems and methods for treating alpha 1-antitrypsin (a1at) deficiency
JP6814155B2 (ja)	2021-01-13	対象とする細胞を選択的に除去する方法及び組成物
JP4063326B2 (ja)	2008-03-19	非天然ヌクレオチドを有するキメラ突然変異性ベクター
JP2022153576A (ja)	2022-10-12	Ｈ１プロモーターを使用するｃｒｉｓｐｒガイドｒｎａの改良を含む組成物および方法
US20180119123A1 (en)	2018-05-03	Crispr/cas-related methods and compositions for treating hiv infection and aids
JP2000509282A (ja)	2000-07-25	突然変異により生じる疾患の治療のための方法および化合物
CA3009727A1 (fr)	2017-07-06	Compositions et methodes de traitement d'hemoglobinopathies
EP3443088A1 (fr)	2019-02-20	Molécules arng de fusion, systèmes d'édition de gènes et leurs procédés d'utilisation
CA2470033A1 (fr)	2003-06-26	Generation intracellulaire d'un adn monocatenaire
US7112405B2 (en)	2006-09-26	Compositions and methods for enhancing oligonucleotide-mediated gene alteration
WO2022056041A2 (fr)	2022-03-17	Édition de base d'arn et d'adn par adar ingéniérisée
AU2001249488C8 (en)	2007-04-19	Targeted chromosomal genomic alterations with modified single stranded oligonucleotides
AU2001249488A1 (en)	2001-12-20	Targeted chromosomal genomic alterations with modified single stranded oligonucleotides
ZA200207742B (en)	2004-06-22	Targeted chromosomal genomic alterations with modified single stranded oligonucleotides.
US20040175722A1 (en)	2004-09-09	Methods and compositions for reducing screening in oligonucleotide-directed nucleic acid sequence alteration
Chin	2010	Triplex-forming peptide nucleic acids as gene modifying agents at the beta-globin locus
HK1244841B (en)	2021-06-25	Methods and compositions for selectively eliminating cells of interest