CA1317244C - Production de formes biologiquement actives de csf a l'aide d'un systeme d'expression baculovirus (acnpv) - cellule d'insecte - Google Patents

Production de formes biologiquement actives de csf a l'aide d'un systeme d'expression baculovirus (acnpv) - cellule d'insecte

Info

Publication number: CA1317244C
Authority: CA; Canada
Prior art keywords: csf; sequence; cells; recombinant baculovirus; baculovirus
Prior art date: 1987-07-24
Legal status (The legal status 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 status listed.): Expired - Lifetime

Application number

CA000572544A

Other languages

English (en)

Inventor

Ernest Seigo Kawasaki

George Martin

Robin Clark

James Joseph Devlin

Edwin C. O'rourke

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Novartis Vaccines and Diagnostics Inc

Original Assignee

Cetus Corp

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.)

1987-07-24

Filing date

1988-07-20

Publication date

1993-05-04

1988-07-20 Application filed by Cetus Corp filed Critical Cetus Corp

1993-05-04 Application granted granted Critical

1993-05-04 Publication of CA1317244C publication Critical patent/CA1317244C/fr

2010-05-04 Anticipated expiration legal-status Critical

Status Expired - Lifetime legal-status Critical Current

Links

241000701447 unidentified baculovirus Species 0.000 title claims description 56
238000004519 manufacturing process Methods 0.000 title claims description 19
230000014509 gene expression Effects 0.000 title abstract description 44
239000013598 vector Substances 0.000 claims abstract description 82
108010046938 Macrophage Colony-Stimulating Factor Proteins 0.000 claims abstract description 70
102000007651 Macrophage Colony-Stimulating Factor Human genes 0.000 claims abstract description 68
241000238631 Hexapoda Species 0.000 claims abstract description 50
238000012546 transfer Methods 0.000 claims abstract description 42
239000013604 expression vector Substances 0.000 claims abstract description 16
241000256251 Spodoptera frugiperda Species 0.000 claims abstract description 5
102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 claims abstract 4
108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 claims abstract 4
108090000623 proteins and genes Proteins 0.000 claims description 94
238000000034 method Methods 0.000 claims description 46
101710182846 Polyhedrin Proteins 0.000 claims description 37
230000000694 effects Effects 0.000 claims description 32
150000001413 amino acids Chemical class 0.000 claims description 30
108091028043 Nucleic acid sequence Proteins 0.000 claims description 26
108020004705 Codon Proteins 0.000 claims description 25
239000013612 plasmid Substances 0.000 claims description 22
102000007644 Colony-Stimulating Factors Human genes 0.000 claims description 21
108010071942 Colony-Stimulating Factors Proteins 0.000 claims description 21
229940047120 colony stimulating factors Drugs 0.000 claims description 11
108091008146 restriction endonucleases Proteins 0.000 claims description 11
108091081024 Start codon Proteins 0.000 claims description 9
108090000765 processed proteins & peptides Proteins 0.000 claims description 7
229920001184 polypeptide Polymers 0.000 claims description 6
102000004196 processed proteins & peptides Human genes 0.000 claims description 6
230000014621 translational initiation Effects 0.000 claims description 5
MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 claims description 4
230000001580 bacterial effect Effects 0.000 claims description 4
239000001963 growth medium Substances 0.000 claims description 4
230000022532 regulation of transcription, DNA-dependent Effects 0.000 claims description 4
241001203868 Autographa californica Species 0.000 claims description 3
241000255896 Galleria mellonella Species 0.000 claims description 2
241001456341 Rachiplusia ou Species 0.000 claims description 2
241000255993 Trichoplusia ni Species 0.000 claims description 2
HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 claims description 2
108020005091 Replication Origin Proteins 0.000 claims 1
210000004027 cell Anatomy 0.000 abstract description 125
239000000539 dimer Substances 0.000 abstract description 6
210000001175 cerebrospinal fluid Anatomy 0.000 abstract 1
102000004169 proteins and genes Human genes 0.000 description 67
235000018102 proteins Nutrition 0.000 description 66
239000012634 fragment Substances 0.000 description 58
239000000523 sample Substances 0.000 description 42
239000002299 complementary DNA Substances 0.000 description 40
108020004414 DNA Proteins 0.000 description 37
235000001014 amino acid Nutrition 0.000 description 35
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 34
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 33
108020004999 messenger RNA Proteins 0.000 description 33
238000010276 construction Methods 0.000 description 29
108091026890 Coding region Proteins 0.000 description 27
241000700605 Viruses Species 0.000 description 25
239000001888 Peptone Substances 0.000 description 21
108010080698 Peptones Proteins 0.000 description 21
125000003275 alpha amino acid group Chemical group 0.000 description 21
150000002632 lipids Chemical class 0.000 description 21
235000019319 peptone Nutrition 0.000 description 21
239000000047 product Substances 0.000 description 20
108091032973 (ribonucleotides)n+m Proteins 0.000 description 19
238000009396 hybridization Methods 0.000 description 19
239000003223 protective agent Substances 0.000 description 19
239000011780 sodium chloride Substances 0.000 description 18
241001529936 Murinae Species 0.000 description 17
239000003995 emulsifying agent Substances 0.000 description 16
208000015181 infectious disease Diseases 0.000 description 16
239000006228 supernatant Substances 0.000 description 16
238000003556 assay Methods 0.000 description 15
239000000872 buffer Substances 0.000 description 15
239000007983 Tris buffer Substances 0.000 description 14
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 14
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 13
DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 13
231100000252 nontoxic Toxicity 0.000 description 13
230000003000 nontoxic effect Effects 0.000 description 13
230000003612 virological effect Effects 0.000 description 13
241000588724 Escherichia coli Species 0.000 description 12
TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 12
230000015572 biosynthetic process Effects 0.000 description 12
230000004048 modification Effects 0.000 description 12
238000012986 modification Methods 0.000 description 12
239000000243 solution Substances 0.000 description 12
QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 11
210000001185 bone marrow Anatomy 0.000 description 11
238000004113 cell culture Methods 0.000 description 11
239000003599 detergent Substances 0.000 description 11
230000009466 transformation Effects 0.000 description 11
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 10
239000000499 gel Substances 0.000 description 10
230000012010 growth Effects 0.000 description 10
238000002360 preparation method Methods 0.000 description 10
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 9
102000004594 DNA Polymerase I Human genes 0.000 description 8
108010017826 DNA Polymerase I Proteins 0.000 description 8
ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 8
239000007640 basal medium Substances 0.000 description 8
230000013595 glycosylation Effects 0.000 description 8
238000006206 glycosylation reaction Methods 0.000 description 8
210000000287 oocyte Anatomy 0.000 description 8
238000002741 site-directed mutagenesis Methods 0.000 description 8
241000894007 species Species 0.000 description 8
DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 8
108091034117 Oligonucleotide Proteins 0.000 description 7
229910019142 PO4 Inorganic materials 0.000 description 7
239000011324 bead Substances 0.000 description 7
238000010367 cloning Methods 0.000 description 7
230000029087 digestion Effects 0.000 description 7
238000000338 in vitro Methods 0.000 description 7
238000011534 incubation Methods 0.000 description 7
210000002540 macrophage Anatomy 0.000 description 7
239000002609 medium Substances 0.000 description 7
239000000203 mixture Substances 0.000 description 7
230000035772 mutation Effects 0.000 description 7
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 7
239000010452 phosphate Substances 0.000 description 7
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
102100031780 Endonuclease Human genes 0.000 description 6
108010042407 Endonucleases Proteins 0.000 description 6
238000000636 Northern blotting Methods 0.000 description 6
108020005187 Oligonucleotide Probes Proteins 0.000 description 6
AIYUHDOJVYHVIT-UHFFFAOYSA-M caesium chloride Chemical compound [Cl-].[Cs+] AIYUHDOJVYHVIT-UHFFFAOYSA-M 0.000 description 6
238000006243 chemical reaction Methods 0.000 description 6
239000003795 chemical substances by application Substances 0.000 description 6
238000002955 isolation Methods 0.000 description 6
229910001629 magnesium chloride Inorganic materials 0.000 description 6
239000000178 monomer Substances 0.000 description 6
239000002773 nucleotide Substances 0.000 description 6
125000003729 nucleotide group Chemical group 0.000 description 6
239000002751 oligonucleotide probe Substances 0.000 description 6
235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 6
229920000053 polysorbate 80 Polymers 0.000 description 6
239000004017 serum-free culture medium Substances 0.000 description 6
238000006467 substitution reaction Methods 0.000 description 6
238000003786 synthesis reaction Methods 0.000 description 6
238000011282 treatment Methods 0.000 description 6
102100031170 CCN family member 3 Human genes 0.000 description 5
102000012410 DNA Ligases Human genes 0.000 description 5
108010061982 DNA Ligases Proteins 0.000 description 5
108010054576 Deoxyribonuclease EcoRI Proteins 0.000 description 5
101000777555 Homo sapiens CCN family member 3 Proteins 0.000 description 5
101001067189 Homo sapiens Plexin-A1 Proteins 0.000 description 5
239000000020 Nitrocellulose Substances 0.000 description 5
108010076504 Protein Sorting Signals Proteins 0.000 description 5
125000000539 amino acid group Chemical group 0.000 description 5
210000002798 bone marrow cell Anatomy 0.000 description 5
238000001516 cell proliferation assay Methods 0.000 description 5
239000001913 cellulose Substances 0.000 description 5
229920002678 cellulose Polymers 0.000 description 5
230000000295 complement effect Effects 0.000 description 5
238000001502 gel electrophoresis Methods 0.000 description 5
229920001220 nitrocellulos Polymers 0.000 description 5
-1 polyoxyethylene Polymers 0.000 description 5
238000012545 processing Methods 0.000 description 5
238000000746 purification Methods 0.000 description 5
230000010076 replication Effects 0.000 description 5
210000002966 serum Anatomy 0.000 description 5
238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 5
238000001890 transfection Methods 0.000 description 5
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 4
JJWSNOOGIUMOEE-UHFFFAOYSA-N Monomethylmercury Chemical compound [Hg]C JJWSNOOGIUMOEE-UHFFFAOYSA-N 0.000 description 4
ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 4
108091036066 Three prime untranslated region Proteins 0.000 description 4
108020005202 Viral DNA Proteins 0.000 description 4
241000269368 Xenopus laevis Species 0.000 description 4
238000013019 agitation Methods 0.000 description 4
238000004458 analytical method Methods 0.000 description 4
230000008901 benefit Effects 0.000 description 4
230000001413 cellular effect Effects 0.000 description 4
239000003638 chemical reducing agent Substances 0.000 description 4
125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 4
230000002708 enhancing effect Effects 0.000 description 4
210000003714 granulocyte Anatomy 0.000 description 4
210000000987 immune system Anatomy 0.000 description 4
230000002458 infectious effect Effects 0.000 description 4
210000004962 mammalian cell Anatomy 0.000 description 4
150000007523 nucleic acids Chemical class 0.000 description 4
235000015097 nutrients Nutrition 0.000 description 4
239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 4
229940068968 polysorbate 80 Drugs 0.000 description 4
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 4
230000008569 process Effects 0.000 description 4
FSYKKLYZXJSNPZ-UHFFFAOYSA-N sarcosine Chemical compound C[NH2+]CC([O-])=O FSYKKLYZXJSNPZ-UHFFFAOYSA-N 0.000 description 4
230000028327 secretion Effects 0.000 description 4
238000012163 sequencing technique Methods 0.000 description 4
230000004936 stimulating effect Effects 0.000 description 4
239000000758 substrate Substances 0.000 description 4
230000014616 translation Effects 0.000 description 4
238000011144 upstream manufacturing Methods 0.000 description 4
241000894006 Bacteria Species 0.000 description 3
108091003079 Bovine Serum Albumin Proteins 0.000 description 3
108020004635 Complementary DNA Proteins 0.000 description 3
108010005054 Deoxyribonuclease BamHI Proteins 0.000 description 3
229920001917 Ficoll Polymers 0.000 description 3
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
101000916628 Homo sapiens Macrophage colony-stimulating factor 1 Proteins 0.000 description 3
101100135355 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pacc-1 gene Proteins 0.000 description 3
240000004808 Saccharomyces cerevisiae Species 0.000 description 3
229920002684 Sepharose Polymers 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
230000004075 alteration Effects 0.000 description 3
230000004071 biological effect Effects 0.000 description 3
210000004369 blood Anatomy 0.000 description 3
239000008280 blood Substances 0.000 description 3
238000005119 centrifugation Methods 0.000 description 3
230000008859 change Effects 0.000 description 3
238000004587 chromatography analysis Methods 0.000 description 3
238000003776 cleavage reaction Methods 0.000 description 3
150000001875 compounds Chemical class 0.000 description 3
239000012228 culture supernatant Substances 0.000 description 3
238000006471 dimerization reaction Methods 0.000 description 3
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 3
238000001962 electrophoresis Methods 0.000 description 3
HQPMKSGTIOYHJT-UHFFFAOYSA-N ethane-1,2-diol;propane-1,2-diol Chemical compound OCCO.CC(O)CO HQPMKSGTIOYHJT-UHFFFAOYSA-N 0.000 description 3
238000012869 ethanol precipitation Methods 0.000 description 3
108010052305 exodeoxyribonuclease III Proteins 0.000 description 3
238000010353 genetic engineering Methods 0.000 description 3
102000053925 human CSF1 Human genes 0.000 description 3
238000003119 immunoblot Methods 0.000 description 3
230000002401 inhibitory effect Effects 0.000 description 3
238000003780 insertion Methods 0.000 description 3
230000037431 insertion Effects 0.000 description 3
239000011159 matrix material Substances 0.000 description 3
239000004530 micro-emulsion Substances 0.000 description 3
238000004264 monolayer culture Methods 0.000 description 3
238000002703 mutagenesis Methods 0.000 description 3
231100000350 mutagenesis Toxicity 0.000 description 3
108091027963 non-coding RNA Proteins 0.000 description 3
102000042567 non-coding RNA Human genes 0.000 description 3
108020004707 nucleic acids Proteins 0.000 description 3
102000039446 nucleic acids Human genes 0.000 description 3
239000002245 particle Substances 0.000 description 3
239000002953 phosphate buffered saline Substances 0.000 description 3
229920001983 poloxamer Polymers 0.000 description 3
229920001993 poloxamer 188 Polymers 0.000 description 3
230000008488 polyadenylation Effects 0.000 description 3
229920005862 polyol Polymers 0.000 description 3
150000003077 polyols Chemical class 0.000 description 3
230000001323 posttranslational effect Effects 0.000 description 3
230000008439 repair process Effects 0.000 description 3
230000007017 scission Effects 0.000 description 3
239000002356 single layer Substances 0.000 description 3
238000004114 suspension culture Methods 0.000 description 3
238000013519 translation Methods 0.000 description 3
241000701366 unidentified nuclear polyhedrosis viruses Species 0.000 description 3
QGVLYPPODPLXMB-UBTYZVCOSA-N (1aR,1bS,4aR,7aS,7bS,8R,9R,9aS)-4a,7b,9,9a-tetrahydroxy-3-(hydroxymethyl)-1,1,6,8-tetramethyl-1,1a,1b,4,4a,7a,7b,8,9,9a-decahydro-5H-cyclopropa[3,4]benzo[1,2-e]azulen-5-one Chemical compound C1=C(CO)C[C@]2(O)C(=O)C(C)=C[C@H]2[C@@]2(O)[C@H](C)[C@@H](O)[C@@]3(O)C(C)(C)[C@H]3[C@@H]21 QGVLYPPODPLXMB-UBTYZVCOSA-N 0.000 description 2
229920001817 Agar Polymers 0.000 description 2
229920000936 Agarose Polymers 0.000 description 2
101100428021 Candida albicans (strain SC5314 / ATCC MYA-2876) UTR2 gene Proteins 0.000 description 2
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
208000003322 Coinfection Diseases 0.000 description 2
102000004533 Endonucleases Human genes 0.000 description 2
102000004190 Enzymes Human genes 0.000 description 2
108090000790 Enzymes Proteins 0.000 description 2
IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 2
101000746367 Homo sapiens Granulocyte colony-stimulating factor Proteins 0.000 description 2
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
108090000467 Interferon-beta Proteins 0.000 description 2
102000000588 Interleukin-2 Human genes 0.000 description 2
108010002350 Interleukin-2 Proteins 0.000 description 2
CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 2
108090000942 Lactalbumin Proteins 0.000 description 2
102000004407 Lactalbumin Human genes 0.000 description 2
102000003960 Ligases Human genes 0.000 description 2
108090000364 Ligases Proteins 0.000 description 2
102000008072 Lymphokines Human genes 0.000 description 2
108010074338 Lymphokines Proteins 0.000 description 2
241001465754 Metazoa Species 0.000 description 2
241000283973 Oryctolagus cuniculus Species 0.000 description 2
229920003171 Poly (ethylene oxide) Polymers 0.000 description 2
108010021757 Polynucleotide 5'-Hydroxyl-Kinase Proteins 0.000 description 2
102000008422 Polynucleotide 5'-hydroxyl-kinase Human genes 0.000 description 2
108010092799 RNA-directed DNA polymerase Proteins 0.000 description 2
102000007056 Recombinant Fusion Proteins Human genes 0.000 description 2
108010008281 Recombinant Fusion Proteins Proteins 0.000 description 2
108010077895 Sarcosine Proteins 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 2
241000269370 Xenopus <genus> Species 0.000 description 2
241000607479 Yersinia pestis Species 0.000 description 2
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 description 2
239000002253 acid Substances 0.000 description 2
150000007513 acids Chemical class 0.000 description 2
239000008272 agar Substances 0.000 description 2
239000011543 agarose gel Substances 0.000 description 2
238000013459 approach Methods 0.000 description 2
235000003704 aspartic acid Nutrition 0.000 description 2
238000013320 baculovirus expression vector system Methods 0.000 description 2
OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 2
239000012148 binding buffer Substances 0.000 description 2
230000033228 biological regulation Effects 0.000 description 2
239000001506 calcium phosphate Substances 0.000 description 2
229910000389 calcium phosphate Inorganic materials 0.000 description 2
235000011010 calcium phosphates Nutrition 0.000 description 2
229940041514 candida albicans extract Drugs 0.000 description 2
230000010261 cell growth Effects 0.000 description 2
230000000973 chemotherapeutic effect Effects 0.000 description 2
YTRQFSDWAXHJCC-UHFFFAOYSA-N chloroform;phenol Chemical class ClC(Cl)Cl.OC1=CC=CC=C1 YTRQFSDWAXHJCC-UHFFFAOYSA-N 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
230000002281 colonystimulating effect Effects 0.000 description 2
239000012141 concentrate Substances 0.000 description 2
235000018417 cysteine Nutrition 0.000 description 2
230000034994 death Effects 0.000 description 2
238000001212 derivatisation Methods 0.000 description 2
238000001514 detection method Methods 0.000 description 2
229960000633 dextran sulfate Drugs 0.000 description 2
230000004069 differentiation Effects 0.000 description 2
238000010790 dilution Methods 0.000 description 2
239000012895 dilution Substances 0.000 description 2
230000003467 diminishing effect Effects 0.000 description 2
238000004090 dissolution Methods 0.000 description 2
230000009977 dual effect Effects 0.000 description 2
230000001804 emulsifying effect Effects 0.000 description 2
108010021310 endodeoxyribonuclease NcoI Proteins 0.000 description 2
238000000605 extraction Methods 0.000 description 2
235000013305 food Nutrition 0.000 description 2
230000006870 function Effects 0.000 description 2
229920000159 gelatin Polymers 0.000 description 2
230000002068 genetic effect Effects 0.000 description 2
YQOKLYTXVFAUCW-UHFFFAOYSA-N guanidine;isothiocyanic acid Chemical compound N=C=S.NC(N)=N YQOKLYTXVFAUCW-UHFFFAOYSA-N 0.000 description 2
238000002744 homologous recombination Methods 0.000 description 2
230000006801 homologous recombination Effects 0.000 description 2
238000002372 labelling Methods 0.000 description 2
239000010410 layer Substances 0.000 description 2
KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 2
210000004185 liver Anatomy 0.000 description 2
238000011068 loading method Methods 0.000 description 2
239000000463 material Substances 0.000 description 2
239000012528 membrane Substances 0.000 description 2
244000005700 microbiome Species 0.000 description 2
239000013642 negative control Substances 0.000 description 2
230000003472 neutralizing effect Effects 0.000 description 2
230000001717 pathogenic effect Effects 0.000 description 2
QGVLYPPODPLXMB-QXYKVGAMSA-N phorbol Natural products C[C@@H]1[C@@H](O)[C@]2(O)[C@H]([C@H]3C=C(CO)C[C@@]4(O)[C@H](C=C(C)C4=O)[C@@]13O)C2(C)C QGVLYPPODPLXMB-QXYKVGAMSA-N 0.000 description 2
229920000642 polymer Polymers 0.000 description 2
229920001451 polypropylene glycol Polymers 0.000 description 2
229920000136 polysorbate Polymers 0.000 description 2
229950008882 polysorbate Drugs 0.000 description 2
238000001556 precipitation Methods 0.000 description 2
230000037452 priming Effects 0.000 description 2
210000001236 prokaryotic cell Anatomy 0.000 description 2
230000002062 proliferating effect Effects 0.000 description 2
230000035755 proliferation Effects 0.000 description 2
238000003259 recombinant expression Methods 0.000 description 2
230000033458 reproduction Effects 0.000 description 2
229940043230 sarcosine Drugs 0.000 description 2
238000013341 scale-up Methods 0.000 description 2
238000012216 screening Methods 0.000 description 2
238000000926 separation method Methods 0.000 description 2
239000011734 sodium Substances 0.000 description 2
229910052708 sodium Inorganic materials 0.000 description 2
239000012064 sodium phosphate buffer Substances 0.000 description 2
239000003381 stabilizer Substances 0.000 description 2
238000010561 standard procedure Methods 0.000 description 2
210000000130 stem cell Anatomy 0.000 description 2
230000000638 stimulation Effects 0.000 description 2
239000000126 substance Substances 0.000 description 2
238000000856 sucrose gradient centrifugation Methods 0.000 description 2
235000000346 sugar Nutrition 0.000 description 2
239000000725 suspension Substances 0.000 description 2
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 2
230000002485 urinary effect Effects 0.000 description 2
230000035899 viability Effects 0.000 description 2
230000029812 viral genome replication Effects 0.000 description 2
239000013603 viral vector Substances 0.000 description 2
239000011782 vitamin Substances 0.000 description 2
229940088594 vitamin Drugs 0.000 description 2
235000013343 vitamin Nutrition 0.000 description 2
229930003231 vitamin Natural products 0.000 description 2
238000005406 washing Methods 0.000 description 2
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
239000012138 yeast extract Substances 0.000 description 2
GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 2
ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 description 1
IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
OIRDTQYFTABQOQ-KQYNXXCUSA-N Adenosine Natural products 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 1
241000282979 Alces alces Species 0.000 description 1
102000002260 Alkaline Phosphatase Human genes 0.000 description 1
108020004774 Alkaline Phosphatase Proteins 0.000 description 1
241001550224 Apha Species 0.000 description 1
241001367049 Autographa Species 0.000 description 1
241000701412 Baculoviridae Species 0.000 description 1
DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 1
241000167854 Bourreria succulenta Species 0.000 description 1
239000002126 C01EB10 - Adenosine Substances 0.000 description 1
101100290380 Caenorhabditis elegans cel-1 gene Proteins 0.000 description 1
UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
241000589877 Campylobacter coli Species 0.000 description 1
241000283707 Capra Species 0.000 description 1
KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
102000053602 DNA Human genes 0.000 description 1
239000003298 DNA probe Substances 0.000 description 1
230000007018 DNA scission Effects 0.000 description 1
244000000626 Daucus carota Species 0.000 description 1
235000002767 Daucus carota Nutrition 0.000 description 1
241000206602 Eukaryota Species 0.000 description 1
108010013216 GATATC-specific type II deoxyribonucleases Proteins 0.000 description 1
241001669573 Galeorhinus galeus Species 0.000 description 1
108010010803 Gelatin Proteins 0.000 description 1
239000001828 Gelatine Substances 0.000 description 1
108700039691 Genetic Promoter Regions Proteins 0.000 description 1
102000003886 Glycoproteins Human genes 0.000 description 1
108090000288 Glycoproteins Proteins 0.000 description 1
IMCHNUANCIGUKS-SRVKXCTJSA-N His-Glu-Arg Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O IMCHNUANCIGUKS-SRVKXCTJSA-N 0.000 description 1
101000746373 Homo sapiens Granulocyte-macrophage colony-stimulating factor Proteins 0.000 description 1
108010001336 Horseradish Peroxidase Proteins 0.000 description 1
108090000144 Human Proteins Proteins 0.000 description 1
102000003839 Human Proteins Human genes 0.000 description 1
241000714260 Human T-lymphotropic virus 1 Species 0.000 description 1
206010062016 Immunosuppression Diseases 0.000 description 1
102100026720 Interferon beta Human genes 0.000 description 1
102000003996 Interferon-beta Human genes 0.000 description 1
102000014150 Interferons Human genes 0.000 description 1
108010050904 Interferons Proteins 0.000 description 1
102000000589 Interleukin-1 Human genes 0.000 description 1
108010002352 Interleukin-1 Proteins 0.000 description 1
101710163270 Nuclease Proteins 0.000 description 1
108700020497 Nucleopolyhedrovirus polyhedrin Proteins 0.000 description 1
108010058846 Ovalbumin Proteins 0.000 description 1
208000002193 Pain Diseases 0.000 description 1
102000035195 Peptidases Human genes 0.000 description 1
108091005804 Peptidases Proteins 0.000 description 1
229920002021 Pluronic® F 77 Polymers 0.000 description 1
229920002025 Pluronic® F 88 Polymers 0.000 description 1
208000037062 Polyps Diseases 0.000 description 1
229920001213 Polysorbate 20 Polymers 0.000 description 1
GOOHAUXETOMSMM-UHFFFAOYSA-N Propylene oxide Chemical compound CC1CO1 GOOHAUXETOMSMM-UHFFFAOYSA-N 0.000 description 1
239000004365 Protease Substances 0.000 description 1
108020004511 Recombinant DNA Proteins 0.000 description 1
102000006382 Ribonucleases Human genes 0.000 description 1
108010083644 Ribonucleases Proteins 0.000 description 1
238000002105 Southern blotting Methods 0.000 description 1
229920002472 Starch Polymers 0.000 description 1
101710172711 Structural protein Proteins 0.000 description 1
108020005038 Terminator Codon Proteins 0.000 description 1
AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
239000004473 Threonine Substances 0.000 description 1
239000007984 Tris EDTA buffer Substances 0.000 description 1
108091023045 Untranslated Region Proteins 0.000 description 1
VIKZGAUAKQZDOF-NRPADANISA-N Val-Ser-Glu Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCC(O)=O VIKZGAUAKQZDOF-NRPADANISA-N 0.000 description 1
108010067390 Viral Proteins Proteins 0.000 description 1
208000036142 Viral infection Diseases 0.000 description 1
NFXWJYUDIOHFAW-UHFFFAOYSA-N acetic acid;tetradecanoic acid Chemical compound CC(O)=O.CCCCCCCCCCCCCC(O)=O NFXWJYUDIOHFAW-UHFFFAOYSA-N 0.000 description 1
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
230000009471 action Effects 0.000 description 1
239000011149 active material Substances 0.000 description 1
229960005305 adenosine Drugs 0.000 description 1
230000001464 adherent effect Effects 0.000 description 1
230000002411 adverse Effects 0.000 description 1
238000000246 agarose gel electrophoresis Methods 0.000 description 1
239000000783 alginic acid Substances 0.000 description 1
235000010443 alginic acid Nutrition 0.000 description 1
229920000615 alginic acid Polymers 0.000 description 1
229960001126 alginic acid Drugs 0.000 description 1
150000004781 alginic acids Chemical class 0.000 description 1
SHGAZHPCJJPHSC-YCNIQYBTSA-N all-trans-retinoic acid Chemical compound OC(=O)\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-YCNIQYBTSA-N 0.000 description 1
229940087168 alpha tocopherol Drugs 0.000 description 1
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 1
229960000723 ampicillin Drugs 0.000 description 1
238000000137 annealing Methods 0.000 description 1
239000002518 antifoaming agent Substances 0.000 description 1
239000012223 aqueous fraction Substances 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
230000003416 augmentation Effects 0.000 description 1
230000003190 augmentative effect Effects 0.000 description 1
235000015278 beef Nutrition 0.000 description 1
IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 1
230000008827 biological function Effects 0.000 description 1
230000002051 biphasic effect Effects 0.000 description 1
210000000988 bone and bone Anatomy 0.000 description 1
KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
239000004327 boric acid Substances 0.000 description 1
229940098773 bovine serum albumin Drugs 0.000 description 1
UDSAIICHUKSCKT-UHFFFAOYSA-N bromophenol blue Chemical compound C1=C(Br)C(O)=C(Br)C=C1C1(C=2C=C(Br)C(O)=C(Br)C=2)C2=CC=CC=C2S(=O)(=O)O1 UDSAIICHUKSCKT-UHFFFAOYSA-N 0.000 description 1
230000005587 bubbling Effects 0.000 description 1
239000007853 buffer solution Substances 0.000 description 1
210000004900 c-terminal fragment Anatomy 0.000 description 1
210000004899 c-terminal region Anatomy 0.000 description 1
239000001110 calcium chloride Substances 0.000 description 1
229910001628 calcium chloride Inorganic materials 0.000 description 1
150000001720 carbohydrates Chemical class 0.000 description 1
239000001569 carbon dioxide Substances 0.000 description 1
229910002092 carbon dioxide Inorganic materials 0.000 description 1
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 1
230000034303 cell budding Effects 0.000 description 1
239000006143 cell culture medium Substances 0.000 description 1
230000005779 cell damage Effects 0.000 description 1
230000030833 cell death Effects 0.000 description 1
208000037887 cell injury Diseases 0.000 description 1
230000006037 cell lysis Effects 0.000 description 1
210000000170 cell membrane Anatomy 0.000 description 1
238000012512 characterization method Methods 0.000 description 1
238000002512 chemotherapy Methods 0.000 description 1
231100000196 chemotoxic Toxicity 0.000 description 1
230000002604 chemotoxic effect Effects 0.000 description 1
235000019693 cherries Nutrition 0.000 description 1
235000015111 chews Nutrition 0.000 description 1
235000012000 cholesterol Nutrition 0.000 description 1
210000000349 chromosome Anatomy 0.000 description 1
239000013599 cloning vector Substances 0.000 description 1
238000000975 co-precipitation Methods 0.000 description 1
239000003026 cod liver oil Substances 0.000 description 1
235000012716 cod liver oil Nutrition 0.000 description 1
230000001332 colony forming effect Effects 0.000 description 1
230000021615 conjugation Effects 0.000 description 1
238000001816 cooling Methods 0.000 description 1
238000012258 culturing Methods 0.000 description 1
XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
230000009089 cytolysis Effects 0.000 description 1
108091092330 cytoplasmic RNA Proteins 0.000 description 1
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 1
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 1
RGWHQCVHVJXOKC-SHYZEUOFSA-J dCTP(4-) Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O)[C@@H](O)C1 RGWHQCVHVJXOKC-SHYZEUOFSA-J 0.000 description 1
NHVNXKFIZYSCEB-XLPZGREQSA-N dTTP Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)C1 NHVNXKFIZYSCEB-XLPZGREQSA-N 0.000 description 1
230000006378 damage Effects 0.000 description 1
238000012217 deletion Methods 0.000 description 1
230000037430 deletion Effects 0.000 description 1
239000003398 denaturant Substances 0.000 description 1
230000001419 dependent effect Effects 0.000 description 1
238000009792 diffusion process Methods 0.000 description 1
AIUDWMLXCFRVDR-UHFFFAOYSA-N dimethyl 2-(3-ethyl-3-methylpentyl)propanedioate Chemical class CCC(C)(CC)CCC(C(=O)OC)C(=O)OC AIUDWMLXCFRVDR-UHFFFAOYSA-N 0.000 description 1
230000003292 diminished effect Effects 0.000 description 1
201000010099 disease Diseases 0.000 description 1
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 1
239000003814 drug Substances 0.000 description 1
238000001035 drying Methods 0.000 description 1
238000004945 emulsification Methods 0.000 description 1
108010051943 endodeoxyribonuclease SspI Proteins 0.000 description 1
238000005516 engineering process Methods 0.000 description 1
230000007613 environmental effect Effects 0.000 description 1
238000009585 enzyme analysis Methods 0.000 description 1
238000001976 enzyme digestion Methods 0.000 description 1
210000002919 epithelial cell Anatomy 0.000 description 1
210000003527 eukaryotic cell Anatomy 0.000 description 1
208000021045 exocrine pancreatic carcinoma Diseases 0.000 description 1
235000013861 fat-free Nutrition 0.000 description 1
230000002349 favourable effect Effects 0.000 description 1
239000012091 fetal bovine serum Substances 0.000 description 1
239000012894 fetal calf serum Substances 0.000 description 1
230000001605 fetal effect Effects 0.000 description 1
239000006260 foam Substances 0.000 description 1
239000012737 fresh medium Substances 0.000 description 1
230000004927 fusion Effects 0.000 description 1
108020001507 fusion proteins Proteins 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
230000036541 health Effects 0.000 description 1
210000000087 hemolymph Anatomy 0.000 description 1
210000005260 human cell Anatomy 0.000 description 1
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
238000005286 illumination Methods 0.000 description 1
238000001114 immunoprecipitation Methods 0.000 description 1
230000001506 immunosuppresive effect Effects 0.000 description 1
230000005764 inhibitory process Effects 0.000 description 1
238000002347 injection Methods 0.000 description 1
239000007924 injection Substances 0.000 description 1
239000002917 insecticide Substances 0.000 description 1
229940079322 interferon Drugs 0.000 description 1
230000003834 intracellular effect Effects 0.000 description 1
230000009545 invasion Effects 0.000 description 1
238000011835 investigation Methods 0.000 description 1
238000011031 large-scale manufacturing process Methods 0.000 description 1
239000000787 lecithin Substances 0.000 description 1
235000010445 lecithin Nutrition 0.000 description 1
229940067606 lecithin Drugs 0.000 description 1
208000032839 leukemia Diseases 0.000 description 1
239000007788 liquid Substances 0.000 description 1
239000012160 loading buffer Substances 0.000 description 1
238000012423 maintenance Methods 0.000 description 1
238000013507 mapping Methods 0.000 description 1
230000007246 mechanism Effects 0.000 description 1
239000012092 media component Substances 0.000 description 1
229920000609 methyl cellulose Polymers 0.000 description 1
230000011987 methylation Effects 0.000 description 1
238000007069 methylation reaction Methods 0.000 description 1
239000001923 methylcellulose Substances 0.000 description 1
235000010981 methylcellulose Nutrition 0.000 description 1
235000013336 milk Nutrition 0.000 description 1
239000008267 milk Substances 0.000 description 1
210000004080 milk Anatomy 0.000 description 1
239000007758 minimum essential medium Substances 0.000 description 1
238000010369 molecular cloning Methods 0.000 description 1
210000001616 monocyte Anatomy 0.000 description 1
230000007935 neutral effect Effects 0.000 description 1
210000000633 nuclear envelope Anatomy 0.000 description 1
210000004940 nucleus Anatomy 0.000 description 1
231100000590 oncogenic Toxicity 0.000 description 1
230000002246 oncogenic effect Effects 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
230000008520 organization Effects 0.000 description 1
229940092253 ovalbumin Drugs 0.000 description 1
230000003647 oxidation Effects 0.000 description 1
238000007254 oxidation reaction Methods 0.000 description 1
229940094443 oxytocics prostaglandins Drugs 0.000 description 1
230000000242 pagocytic effect Effects 0.000 description 1
230000036407 pain Effects 0.000 description 1
208000008443 pancreatic carcinoma Diseases 0.000 description 1
230000036961 partial effect Effects 0.000 description 1
239000008188 pellet Substances 0.000 description 1
NRNCYVBFPDDJNE-UHFFFAOYSA-N pemoline Chemical compound O1C(N)=NC(=O)C1C1=CC=CC=C1 NRNCYVBFPDDJNE-UHFFFAOYSA-N 0.000 description 1
229940066779 peptones Drugs 0.000 description 1
239000000575 pesticide Substances 0.000 description 1
238000002205 phenol-chloroform extraction Methods 0.000 description 1
150000003904 phospholipids Chemical class 0.000 description 1
230000007505 plaque formation Effects 0.000 description 1
229920002401 polyacrylamide Polymers 0.000 description 1
239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
229920006316 polyvinylpyrrolidine Polymers 0.000 description 1
239000001267 polyvinylpyrrolidone Substances 0.000 description 1
229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
239000002243 precursor Substances 0.000 description 1
150000003180 prostaglandins Chemical class 0.000 description 1
230000001681 protective effect Effects 0.000 description 1
230000009993 protective function Effects 0.000 description 1
230000002797 proteolythic effect Effects 0.000 description 1
238000011084 recovery Methods 0.000 description 1
230000009467 reduction Effects 0.000 description 1
230000002829 reductive effect Effects 0.000 description 1
230000001105 regulatory effect Effects 0.000 description 1
230000003362 replicative effect Effects 0.000 description 1
230000004044 response Effects 0.000 description 1
229930002330 retinoic acid Natural products 0.000 description 1
230000002441 reversible effect Effects 0.000 description 1
239000002342 ribonucleoside Substances 0.000 description 1
239000012146 running buffer Substances 0.000 description 1
229920006395 saturated elastomer Polymers 0.000 description 1
150000004671 saturated fatty acids Chemical group 0.000 description 1
230000003248 secreting effect Effects 0.000 description 1
238000003375 selectivity assay Methods 0.000 description 1
125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 1
239000012679 serum free medium Substances 0.000 description 1
238000012807 shake-flask culturing Methods 0.000 description 1
239000001488 sodium phosphate Substances 0.000 description 1
229910000162 sodium phosphate Inorganic materials 0.000 description 1
239000001593 sorbitan monooleate Substances 0.000 description 1
235000011069 sorbitan monooleate Nutrition 0.000 description 1
229940035049 sorbitan monooleate Drugs 0.000 description 1
238000001228 spectrum Methods 0.000 description 1
230000007480 spreading Effects 0.000 description 1
238000003892 spreading Methods 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
239000007858 starting material Substances 0.000 description 1
230000001954 sterilising effect Effects 0.000 description 1
238000004659 sterilization and disinfection Methods 0.000 description 1
150000008163 sugars Chemical class 0.000 description 1
239000013589 supplement Substances 0.000 description 1
230000001629 suppression Effects 0.000 description 1
230000001360 synchronised effect Effects 0.000 description 1
238000001308 synthesis method Methods 0.000 description 1
230000002123 temporal effect Effects 0.000 description 1
238000012360 testing method Methods 0.000 description 1
229940104230 thymidine Drugs 0.000 description 1
229960000984 tocofersolan Drugs 0.000 description 1
231100000331 toxic Toxicity 0.000 description 1
230000002588 toxic effect Effects 0.000 description 1
238000000844 transformation Methods 0.000 description 1
230000001131 transforming effect Effects 0.000 description 1
230000001052 transient effect Effects 0.000 description 1
230000010474 transient expression Effects 0.000 description 1
229960001727 tretinoin Drugs 0.000 description 1
150000005691 triesters Chemical class 0.000 description 1
239000001226 triphosphate Substances 0.000 description 1
235000011178 triphosphate Nutrition 0.000 description 1
125000002264 triphosphate group Chemical class [H]OP(=O)(O[H])OP(=O)(O[H])OP(=O)(O[H])O* 0.000 description 1
RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
210000004881 tumor cell Anatomy 0.000 description 1
235000021122 unsaturated fatty acids Nutrition 0.000 description 1
150000004670 unsaturated fatty acids Chemical group 0.000 description 1
210000002438 upper gastrointestinal tract Anatomy 0.000 description 1
238000012795 verification Methods 0.000 description 1
230000009385 viral infection Effects 0.000 description 1
230000017613 viral reproduction Effects 0.000 description 1
230000000007 visual effect Effects 0.000 description 1
238000003260 vortexing Methods 0.000 description 1
239000011534 wash buffer Substances 0.000 description 1
229920003169 water-soluble polymer Polymers 0.000 description 1
210000005253 yeast cell Anatomy 0.000 description 1
239000002076 α-tocopherol Substances 0.000 description 1
235000004835 α-tocopherol Nutrition 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
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
- C12N15/86—Viral vectors
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/52—Cytokines; Lymphokines; Interferons
- C07K14/53—Colony-stimulating factor [CSF]
- C07K14/535—Granulocyte CSF; Granulocyte-macrophage CSF
- 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
- C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
- C12N2710/00011—Details
- C12N2710/14011—Baculoviridae
- C12N2710/14111—Nucleopolyhedrovirus, e.g. autographa californica nucleopolyhedrovirus
- C12N2710/14141—Use of virus, viral particle or viral elements as a vector
- C12N2710/14143—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector

Landscapes

Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Genetics & Genomics (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Engineering & Computer Science (AREA)
Zoology (AREA)
Bioinformatics & Cheminformatics (AREA)
Biotechnology (AREA)
General Engineering & Computer Science (AREA)
Molecular Biology (AREA)
General Health & Medical Sciences (AREA)
Biophysics (AREA)
Biochemistry (AREA)
Wood Science & Technology (AREA)
Biomedical Technology (AREA)
Physics & Mathematics (AREA)
Microbiology (AREA)
Plant Pathology (AREA)
Virology (AREA)
Immunology (AREA)
Toxicology (AREA)
Gastroenterology & Hepatology (AREA)
Medicinal Chemistry (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Preparation Of Compounds By Using Micro-Organisms (AREA)
Peptides Or Proteins (AREA)

CA000572544A 1987-07-24 1988-07-20 Production de formes biologiquement actives de csf a l'aide d'un systeme d'expression baculovirus (acnpv) - cellule d'insecte Expired - Lifetime CA1317244C (fr)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US7718887A	1987-07-24	1987-07-24
US077,188		1987-07-24

Publications (1)

Publication Number	Publication Date
CA1317244C true CA1317244C (fr)	1993-05-04

Family

ID=22136589

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA000572544A Expired - Lifetime CA1317244C (fr)	1987-07-24	1988-07-20	Production de formes biologiquement actives de csf a l'aide d'un systeme d'expression baculovirus (acnpv) - cellule d'insecte

Country Status (3)

Country	Link
AU (1)	AU2251488A (fr)
CA (1)	CA1317244C (fr)
WO (1)	WO1989001038A1 (fr)

Families Citing this family (31)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JPH04228066A (ja) *	1990-10-23	1992-08-18	Rikagaku Kenkyusho	外来遺伝子発現用培養細胞
US6342216B1 (en) *	1999-03-17	2002-01-29	The Board Of Regents, The University Of Texas System	Therapy of cancer by insect cells containing recombinant baculovirus encoding genes
US6872385B2 (en)	2000-05-31	2005-03-29	Board Of Regents, The University Of Texas System	Adjuvant preparation for the induction of specific immunity
AU2005319099B2 (en)	2004-02-02	2010-09-16	Ambrx, Inc.	Modified human growth hormone
CN103755800B (zh)	2004-02-02	2016-02-24	Ambrx公司	经修饰的人类生长激素多肽与其用途
CN102532321B (zh)	2004-06-18	2018-10-12	Ambrx公司	新颖抗原结合多肽和其用途
US7638299B2 (en)	2004-07-21	2009-12-29	Ambrx, Inc.	Biosynthetic polypeptides utilizing non-naturally encoded amino acids
KR101224781B1 (ko)	2004-12-22	2013-01-21	암브룩스, 인코포레이티드	비천연적으로 코딩된 아미노산을 포함하는 인간 성장호르몬의 조제물
US7385028B2 (en)	2004-12-22	2008-06-10	Ambrx, Inc	Derivatization of non-natural amino acids and polypeptides
AU2005323106B2 (en)	2004-12-22	2010-07-29	Ambrx, Inc.	Methods for expression and purification of recombinant human growth hormone
NZ555425A (en)	2004-12-22	2010-04-30	Ambrx Inc	Compositions of aminoacyl-tRNA synthetase and uses thereof
WO2006133088A2 (fr)	2005-06-03	2006-12-14	Ambrx, Inc.	Molecules d'interferons humains ameliorees et utilisations de celles-ci
CA2618878C (fr)	2005-08-18	2016-06-28	Ambrx, Inc.	Compositions d'arnt et leurs utilisations
EP1951890A4 (fr)	2005-11-16	2009-06-24	Ambrx Inc	Procedes et compositions comprenant des acides amines non naturels
WO2008030558A2 (fr)	2006-09-08	2008-03-13	Ambrx, Inc.	Polypeptide plasmatique humain modifié ou squelettes de fc et leurs utilisations
ES2457527T3 (es)	2006-09-08	2014-04-28	Ambrx, Inc.	ARNt Supresor hibrido en células de vertebrados
PT2064333E (pt)	2006-09-08	2014-06-09	Ambrx Inc	Supressor híbrido arnt para células de vertebrados
KR101476472B1 (ko)	2007-03-30	2015-01-05	암브룩스, 인코포레이티드	변형된 ｆｇｆ-21 폴리펩티드 및 그 용도
KR20100019467A (ko)	2007-05-02	2010-02-18	암브룩스, 인코포레이티드	변형된 인터페론 베타 폴리펩티드 및 그의 용도
ES2632504T3 (es)	2007-11-20	2017-09-13	Ambrx, Inc.	Polipéptidos de insulina modificados y sus usos
NZ602170A (en)	2008-02-08	2014-03-28	Ambrx Inc	Modified leptin polypeptides and their uses
MX2011000859A (es)	2008-07-23	2011-02-24	Ambrx Inc	Polipeptidos g-csf bovinos modificados y sus usos.
NO2337846T3 (fr)	2008-09-26	2018-06-16
PL2342223T3 (pl)	2008-09-26	2017-09-29	Ambrx, Inc.	Zmodyfikowane polipeptydy zwierzęcej erytropoetyny i ich zastosowania
EP2516455A4 (fr)	2009-12-21	2013-05-22	Ambrx Inc	Polypeptides d'hormone de croissance porcine modifiée et leurs utilisations
NZ600361A (en)	2009-12-21	2014-06-27	Ambrx Inc	Modified bovine somatotropin polypeptides and their uses
US9567386B2 (en)	2010-08-17	2017-02-14	Ambrx, Inc.	Therapeutic uses of modified relaxin polypeptides
SMT201900495T1 (it)	2010-08-17	2019-11-13	Ambrx Inc	Polipeptidi di relaxina modificati e loro usi
TWI480288B (zh)	2010-09-23	2015-04-11	Lilly Co Eli	牛顆粒細胞群落刺激因子及其變體之調配物
BR112017008157A2 (pt)	2014-10-24	2017-12-19	Bristol Myers Squibb Co	polipeptídeos de fgf-21 modificados e usos dos mesmos
US10266578B2 (en)	2017-02-08	2019-04-23	Bristol-Myers Squibb Company	Modified relaxin polypeptides comprising a pharmacokinetic enhancer and uses thereof

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
ATE78293T1 (de) *	1983-05-27	1992-08-15	Texas A & M Univ Sys	Verfahren zur herstellung eines rekombinanten baculovirus-expressionsvektors.
NZ212645A (en) *	1984-07-06	1990-02-26	Sandoz Ltd	Method for producing primate granulocyte-macrophage colony stimulating factor (gm-csf)
WO1988003173A2 (fr) *	1986-10-24	1988-05-05	Cetus Corporation	Nouvelles formes du facteur-1 de stimulation de colonies

1988
- 1988-07-20 WO PCT/US1988/002445 patent/WO1989001038A1/fr not_active Ceased
- 1988-07-20 CA CA000572544A patent/CA1317244C/fr not_active Expired - Lifetime
- 1988-07-20 AU AU22514/88A patent/AU2251488A/en not_active Abandoned

Also Published As

Publication number	Publication date
WO1989001038A1 (fr)	1989-02-09
AU2251488A (en)	1989-03-01

Legal Events

Date	Code	Title	Description
2010-05-04	MKLA	Lapsed
2012-12-05	MKEC	Expiry (correction)	Effective date: 20121205

Publication	Publication Date	Title
WO1989001038A1 (fr)	1989-02-09	PRODUCTION DE FORMES BIOLOGIQUEMENT ACTIVES DE CSF UTILISANT UN SYSTEME D'EXPRESSION DE CELLULES D'INSECTES-BACULOVIRUS (AcNPV)
EP0255231B1 (fr)	1992-05-20	Gène humain d'érythropoiétine: expression à haut niveau dans des cellules de mammifères transférées de façon stable
JP2957974B2 (ja)	1999-10-06	エリスロポエチン活性を有するタンパク質の製造方法
Wojchowski et al.	1987	Active human erythropoietin expressed in insect cells using a baculovirus vector: a role for N-linked oligosaccharide
US4965195A (en)	1990-10-23	Interleukin-7
JP2898291B2 (ja)	1999-05-31	昆虫細胞の増殖およびそれによる生産物の発現のための無血清培地
DE69535680T2 (de)	2008-12-11	Sekretierte, als impfstoffe und diagnostika verwendbare virale cmv-proteine
US6156301A (en)	2000-12-05	Use of interleukin-7 to stimulate proliferation of hematopoietic cell precursors
HU216079B (hu)	1999-04-28	Eljárás eritropoietin előállítására
FI103987B (fi)	1999-10-29	Interleukiini-7
IE58011B1 (en)	1993-06-16	Method for producing a recombinant baculovirus expression vector
JP2515399B2 (ja)	1996-07-10	ヒト神経成長因子
US5972886A (en)	1999-10-26	Megakaryocyte differentiation factor
DE3853139T2 (de)	1995-06-14	Rekombinanter, fremde gene enthaltender menschlicher cytomegalovirus und seine verwendung.
EP0118977A1 (fr)	1984-09-19	Séquences d'ADN, molécules recombinantes d'ADN et procédés pour la production des polypeptides semblables à interleukin-2 humain
KR970003518B1 (ko)	1997-03-18	신규 영장류 조혈성장인자족(family)
AU1496688A (en)	1988-08-10	Human interleukin-3 proteins
KR100218818B1 (ko)	1999-10-01	항-트롬빈 폴리펩타이드
AU599348B2 (en)	1990-07-19	Method for producing selected polypeptides in virally infected insect cells and polypeptides isolated therefrom
JPH0365191A (ja)	1991-03-20	スフェロイジン単離ｄｎａおよび組み換え昆虫ポックスウィルス発現ベクター
AU713681B2 (en)	1999-12-09	Use of the intracytoplasmic domain of the prolactin receptor or the growth hormone receptor for achieving protein secretion
US5888817A (en)	1999-03-30	Pituitary differentiaton factor and methods of use thereof
AU602097B2 (en)	1990-09-27	Bovine granulocyte-macrophage colony stimulating factor
DE3910084A1 (de)	1989-11-16	Polypeptide mit wachstumsfaktor-aktivitaet und nukleinsaeuresequenzen
GB2276622A (en)	1994-10-05	Mollusc polypeptides as insecticides, and DNA thereof