NO320349B1 - Modufiserte soppceller, fremgangsmate for fremstilling av rekombinante produkter, DNA-molekyl og anvendelse av slike. - Google Patents
Modufiserte soppceller, fremgangsmate for fremstilling av rekombinante produkter, DNA-molekyl og anvendelse av slike. Download PDFInfo
- Publication number
- NO320349B1 NO320349B1 NO19950534A NO950534A NO320349B1 NO 320349 B1 NO320349 B1 NO 320349B1 NO 19950534 A NO19950534 A NO 19950534A NO 950534 A NO950534 A NO 950534A NO 320349 B1 NO320349 B1 NO 320349B1
- Authority
- NO
- Norway
- Prior art keywords
- dna
- fungal cell
- sequence
- gene
- protein
- Prior art date
Links
- 230000002538 fungal effect Effects 0.000 title claims abstract description 83
- 238000000034 method Methods 0.000 title claims abstract description 25
- 108020004414 DNA Proteins 0.000 title claims description 80
- 102000053602 DNA Human genes 0.000 title claims description 9
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 111
- 102000004169 proteins and genes Human genes 0.000 claims abstract description 50
- 108091028043 Nucleic acid sequence Proteins 0.000 claims abstract description 26
- 230000004048 modification Effects 0.000 claims abstract description 12
- 238000012986 modification Methods 0.000 claims abstract description 12
- 210000004027 cell Anatomy 0.000 claims description 136
- 239000012634 fragment Substances 0.000 claims description 62
- 240000004808 Saccharomyces cerevisiae Species 0.000 claims description 24
- 230000004989 O-glycosylation Effects 0.000 claims description 20
- 230000000694 effects Effects 0.000 claims description 20
- 238000004519 manufacturing process Methods 0.000 claims description 20
- 101150092906 pmt1 gene Proteins 0.000 claims description 19
- 108010087568 Mannosyltransferases Proteins 0.000 claims description 16
- 102000006722 Mannosyltransferases Human genes 0.000 claims description 16
- 238000012239 gene modification Methods 0.000 claims description 16
- 241001138401 Kluyveromyces lactis Species 0.000 claims description 15
- 239000013598 vector Substances 0.000 claims description 15
- 102000004190 Enzymes Human genes 0.000 claims description 14
- 108090000790 Enzymes Proteins 0.000 claims description 14
- 230000005017 genetic modification Effects 0.000 claims description 14
- 235000013617 genetically modified food Nutrition 0.000 claims description 14
- 238000009396 hybridization Methods 0.000 claims description 14
- 108091029865 Exogenous DNA Proteins 0.000 claims description 13
- 239000002773 nucleotide Substances 0.000 claims description 13
- 125000003729 nucleotide group Chemical group 0.000 claims description 13
- 125000000311 mannosyl group Chemical group C1([C@@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 claims description 12
- 239000000523 sample Substances 0.000 claims description 12
- 125000002842 L-seryl group Chemical group O=C([*])[C@](N([H])[H])([H])C([H])([H])O[H] 0.000 claims description 10
- 241000235649 Kluyveromyces Species 0.000 claims description 9
- 101100241858 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) OAC1 gene Proteins 0.000 claims description 9
- 108091026890 Coding region Proteins 0.000 claims description 8
- 238000006243 chemical reaction Methods 0.000 claims description 8
- 230000002068 genetic effect Effects 0.000 claims description 8
- 241000235070 Saccharomyces Species 0.000 claims description 7
- 238000012217 deletion Methods 0.000 claims description 7
- 230000037430 deletion Effects 0.000 claims description 7
- 238000013518 transcription Methods 0.000 claims description 7
- 241000233866 Fungi Species 0.000 claims description 6
- 238000007792 addition Methods 0.000 claims description 6
- 230000035897 transcription Effects 0.000 claims description 5
- 238000013519 translation Methods 0.000 claims description 5
- 230000004071 biological effect Effects 0.000 claims description 4
- 230000015572 biosynthetic process Effects 0.000 claims description 4
- 210000000349 chromosome Anatomy 0.000 claims description 4
- 230000037361 pathway Effects 0.000 claims description 4
- 230000022532 regulation of transcription, DNA-dependent Effects 0.000 claims description 4
- 238000005204 segregation Methods 0.000 claims description 3
- 238000006467 substitution reaction Methods 0.000 claims description 3
- 230000001629 suppression Effects 0.000 claims description 3
- 238000003786 synthesis reaction Methods 0.000 claims description 3
- 108010076504 Protein Sorting Signals Proteins 0.000 claims description 2
- 238000003780 insertion Methods 0.000 claims description 2
- 230000037431 insertion Effects 0.000 claims description 2
- 230000000869 mutational effect Effects 0.000 claims description 2
- 230000003248 secreting effect Effects 0.000 claims description 2
- 230000000977 initiatory effect Effects 0.000 claims 2
- 125000003275 alpha amino acid group Chemical group 0.000 claims 1
- 239000000047 product Substances 0.000 description 30
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 20
- 108091034117 Oligonucleotide Proteins 0.000 description 16
- 108090000765 processed proteins & peptides Proteins 0.000 description 16
- 239000000463 material Substances 0.000 description 13
- 239000013612 plasmid Substances 0.000 description 13
- 102000004196 processed proteins & peptides Human genes 0.000 description 13
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 101100408676 Caenorhabditis elegans pmt-1 gene Proteins 0.000 description 11
- 101150050575 URA3 gene Proteins 0.000 description 11
- 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 11
- 239000000872 buffer Substances 0.000 description 11
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 10
- 238000004458 analytical method Methods 0.000 description 10
- 229940088598 enzyme Drugs 0.000 description 10
- 238000012163 sequencing technique Methods 0.000 description 10
- 101100246753 Halobacterium salinarum (strain ATCC 700922 / JCM 11081 / NRC-1) pyrF gene Proteins 0.000 description 9
- 150000001413 amino acids Chemical group 0.000 description 9
- 239000002609 medium Substances 0.000 description 9
- 238000002105 Southern blotting Methods 0.000 description 8
- 150000001720 carbohydrates Chemical group 0.000 description 8
- 238000006206 glycosylation reaction Methods 0.000 description 8
- 239000012528 membrane Substances 0.000 description 8
- 101710117373 92 kDa protein Proteins 0.000 description 7
- 241000972773 Aulopiformes Species 0.000 description 7
- 238000010276 construction Methods 0.000 description 7
- 230000004927 fusion Effects 0.000 description 7
- 239000011521 glass Substances 0.000 description 7
- 235000019515 salmon Nutrition 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 239000000020 Nitrocellulose Substances 0.000 description 6
- 230000029087 digestion Effects 0.000 description 6
- 229920001220 nitrocellulos Polymers 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 230000009466 transformation Effects 0.000 description 6
- 238000012408 PCR amplification Methods 0.000 description 5
- 239000007983 Tris buffer Substances 0.000 description 5
- 239000000499 gel Substances 0.000 description 5
- 230000013595 glycosylation Effects 0.000 description 5
- 238000000338 in vitro Methods 0.000 description 5
- 238000002955 isolation Methods 0.000 description 5
- 229940046166 oligodeoxynucleotide Drugs 0.000 description 5
- 229920001184 polypeptide Polymers 0.000 description 5
- 108091008146 restriction endonucleases Proteins 0.000 description 5
- 125000002072 seryl group Chemical group 0.000 description 5
- -1 threonyl amino acids Chemical class 0.000 description 5
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 5
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 4
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 102000003886 Glycoproteins Human genes 0.000 description 4
- 108090000288 Glycoproteins Proteins 0.000 description 4
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 4
- 241000235648 Pichia Species 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 229930006000 Sucrose Natural products 0.000 description 4
- 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 4
- 102000004142 Trypsin Human genes 0.000 description 4
- 108090000631 Trypsin Proteins 0.000 description 4
- IPAOLVGASNLKMS-WIFKHAHXSA-N [(6e,10e,14e,18e,22e,26e,30e,34e,38e,42e,46e,50e,54e,58e,62e,66e,70e,74e)-3,7,11,15,19,23,27,31,35,39,43,47,51,55,59,63,67,71,75,79-icosamethyloctaconta-6,10,14,18,22,26,30,34,38,42,46,50,54,58,62,66,70,74,78-nonadecaenyl] [(2s,3s,4s,5s,6r)-3,4,5-trihydro Chemical compound CC(C)=CCCC(/C)=C/CCC(/C)=C/CCC(/C)=C/CCC(/C)=C/CCC(/C)=C/CCC(/C)=C/CCC(/C)=C/CCC(/C)=C/CCC(/C)=C/CCC(/C)=C/CCC(/C)=C/CCC(/C)=C/CCC(/C)=C/CCC(/C)=C/CCC(/C)=C/CCC(/C)=C/CCC(/C)=C/CCC(/C)=C/CCC(C)CCOP(O)(=O)O[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@@H]1O IPAOLVGASNLKMS-WIFKHAHXSA-N 0.000 description 4
- 230000003321 amplification Effects 0.000 description 4
- 239000011324 bead Substances 0.000 description 4
- AIYUHDOJVYHVIT-UHFFFAOYSA-M caesium chloride Chemical compound [Cl-].[Cs+] AIYUHDOJVYHVIT-UHFFFAOYSA-M 0.000 description 4
- 235000014633 carbohydrates Nutrition 0.000 description 4
- 238000003776 cleavage reaction Methods 0.000 description 4
- 238000010367 cloning Methods 0.000 description 4
- 230000008878 coupling Effects 0.000 description 4
- 238000010168 coupling process Methods 0.000 description 4
- 238000005859 coupling reaction Methods 0.000 description 4
- 238000003379 elimination reaction Methods 0.000 description 4
- 238000005516 engineering process Methods 0.000 description 4
- 230000012010 growth Effects 0.000 description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 230000007246 mechanism Effects 0.000 description 4
- 238000003199 nucleic acid amplification method Methods 0.000 description 4
- 229920001542 oligosaccharide Polymers 0.000 description 4
- 150000002482 oligosaccharides Chemical class 0.000 description 4
- 230000007017 scission Effects 0.000 description 4
- 210000002966 serum Anatomy 0.000 description 4
- 239000005720 sucrose Substances 0.000 description 4
- 239000012588 trypsin Substances 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- 238000001262 western blot Methods 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 108010021809 Alcohol dehydrogenase Proteins 0.000 description 3
- 108010025188 Alcohol oxidase Proteins 0.000 description 3
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 3
- 229910000013 Ammonium bicarbonate Inorganic materials 0.000 description 3
- 108091033380 Coding strand Proteins 0.000 description 3
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 3
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 3
- 102000010780 Platelet-Derived Growth Factor Human genes 0.000 description 3
- 108010038512 Platelet-Derived Growth Factor Proteins 0.000 description 3
- 108020004511 Recombinant DNA Proteins 0.000 description 3
- 238000012300 Sequence Analysis Methods 0.000 description 3
- 239000011543 agarose gel Substances 0.000 description 3
- 235000012538 ammonium bicarbonate Nutrition 0.000 description 3
- 239000001099 ammonium carbonate Substances 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- 230000008030 elimination Effects 0.000 description 3
- 239000008188 pellet Substances 0.000 description 3
- 238000012216 screening Methods 0.000 description 3
- 230000028327 secretion Effects 0.000 description 3
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 102000007698 Alcohol dehydrogenase Human genes 0.000 description 2
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 2
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 2
- 241000222120 Candida <Saccharomycetales> Species 0.000 description 2
- 241000588724 Escherichia coli Species 0.000 description 2
- 108700039691 Genetic Promoter Regions Proteins 0.000 description 2
- 108700007698 Genetic Terminator Regions Proteins 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- 238000000636 Northern blotting Methods 0.000 description 2
- 102000011755 Phosphoglycerate Kinase Human genes 0.000 description 2
- 102000012288 Phosphopyruvate Hydratase Human genes 0.000 description 2
- 108010022181 Phosphopyruvate Hydratase Proteins 0.000 description 2
- 239000012722 SDS sample buffer Substances 0.000 description 2
- 229920002684 Sepharose Polymers 0.000 description 2
- 101001099217 Thermotoga maritima (strain ATCC 43589 / DSM 3109 / JCM 10099 / NBRC 100826 / MSB8) Triosephosphate isomerase Proteins 0.000 description 2
- 240000004922 Vigna radiata Species 0.000 description 2
- 235000010721 Vigna radiata var radiata Nutrition 0.000 description 2
- 235000011469 Vigna radiata var sublobata Nutrition 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 238000001042 affinity chromatography Methods 0.000 description 2
- 230000000890 antigenic effect Effects 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 210000002421 cell wall Anatomy 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- 238000007385 chemical modification Methods 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 238000011109 contamination Methods 0.000 description 2
- 238000004925 denaturation Methods 0.000 description 2
- 230000036425 denaturation Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- FRTGEIHSCHXMTI-UHFFFAOYSA-N dimethyl octanediimidate Chemical compound COC(=N)CCCCCCC(=N)OC FRTGEIHSCHXMTI-UHFFFAOYSA-N 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000004520 electroporation Methods 0.000 description 2
- 230000002255 enzymatic effect Effects 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 238000001502 gel electrophoresis Methods 0.000 description 2
- 102000006602 glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 2
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 2
- 239000003102 growth factor Substances 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 230000006801 homologous recombination Effects 0.000 description 2
- 238000002744 homologous recombination Methods 0.000 description 2
- 229910052588 hydroxylapatite Inorganic materials 0.000 description 2
- 230000001900 immune effect Effects 0.000 description 2
- 238000010348 incorporation Methods 0.000 description 2
- 238000011534 incubation Methods 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
- 230000010354 integration Effects 0.000 description 2
- 230000010039 intracellular degradation Effects 0.000 description 2
- 238000002372 labelling Methods 0.000 description 2
- 238000011031 large-scale manufacturing process Methods 0.000 description 2
- 229910001629 magnesium chloride Inorganic materials 0.000 description 2
- 108020004999 messenger RNA Proteins 0.000 description 2
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000003471 mutagenic agent Substances 0.000 description 2
- LRMQCJCMKQSEJD-UHFFFAOYSA-N oligo b Polymers O1C(N2C3=NC=NC(N)=C3N=C2)C(OC)C(OC(=O)C=2C=C3C4(OC(=O)C3=CC=2)C2=CC=C(O)C=C2OC2=CC(O)=CC=C24)C1COP(O)(=O)OC1C(C(O2)N3C(N=C(N)C(C)=C3)=O)OCC12COP(O)(=O)OC(C1OC)C(COP(O)(=O)OC2C3(COP(O)(=O)OC4C(C(OC4COP(O)(=O)OC4C(C(OC4COP(O)(=O)OC4C(C(OC4COP(O)(=O)OC4C5(COP(O)(=O)OC6C(C(OC6COP(O)(=O)OC6C7(COP(O)(=O)OC8C(C(OC8COP(O)(=O)OC8C9(CO)COC8C(O9)N8C(N=C(N)C(C)=C8)=O)N8C(NC(=O)C=C8)=O)OC)COC6C(O7)N6C(N=C(N)C(C)=C6)=O)N6C(N=C(N)C=C6)=O)OC)COC4C(O5)N4C(N=C(N)C(C)=C4)=O)N4C5=NC=NC(N)=C5N=C4)OC)N4C5=C(C(NC(N)=N5)=O)N=C4)OC)N4C5=C(C(NC(N)=N5)=O)N=C4)OC)COC2C(O3)N2C(N=C(N)C(C)=C2)=O)OC1N1C=CC(=O)NC1=O LRMQCJCMKQSEJD-UHFFFAOYSA-N 0.000 description 2
- XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 description 2
- 238000006116 polymerization reaction Methods 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 230000002285 radioactive effect Effects 0.000 description 2
- 230000003362 replicative effect Effects 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 238000000527 sonication Methods 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 230000005026 transcription initiation Effects 0.000 description 2
- 230000014621 translational initiation Effects 0.000 description 2
- 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 1
- ICBQXEWYZVQCFH-UHFFFAOYSA-N 3-(4-bromoanilino)-n,n-dimethylpropanamide Chemical compound CN(C)C(=O)CCNC1=CC=C(Br)C=C1 ICBQXEWYZVQCFH-UHFFFAOYSA-N 0.000 description 1
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 1
- UHPMCKVQTMMPCG-UHFFFAOYSA-N 5,8-dihydroxy-2-methoxy-6-methyl-7-(2-oxopropyl)naphthalene-1,4-dione Chemical compound CC1=C(CC(C)=O)C(O)=C2C(=O)C(OC)=CC(=O)C2=C1O UHPMCKVQTMMPCG-UHFFFAOYSA-N 0.000 description 1
- 208000030507 AIDS Diseases 0.000 description 1
- 108010051457 Acid Phosphatase Proteins 0.000 description 1
- 241001136782 Alca Species 0.000 description 1
- 108090000531 Amidohydrolases Proteins 0.000 description 1
- 102000004092 Amidohydrolases Human genes 0.000 description 1
- 102000013142 Amylases Human genes 0.000 description 1
- 108010065511 Amylases Proteins 0.000 description 1
- 102000007592 Apolipoproteins Human genes 0.000 description 1
- 108010071619 Apolipoproteins Proteins 0.000 description 1
- 241000228212 Aspergillus Species 0.000 description 1
- 244000063299 Bacillus subtilis Species 0.000 description 1
- 235000014469 Bacillus subtilis Nutrition 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 101100275473 Caenorhabditis elegans ctc-3 gene Proteins 0.000 description 1
- 102100035882 Catalase Human genes 0.000 description 1
- 108010053835 Catalase Proteins 0.000 description 1
- 108010008885 Cellulose 1,4-beta-Cellobiosidase Proteins 0.000 description 1
- 108090000746 Chymosin Proteins 0.000 description 1
- 108020004705 Codon Proteins 0.000 description 1
- 108700010070 Codon Usage Proteins 0.000 description 1
- 108020004635 Complementary DNA Proteins 0.000 description 1
- 241000186216 Corynebacterium Species 0.000 description 1
- 241000701022 Cytomegalovirus Species 0.000 description 1
- 102000012410 DNA Ligases Human genes 0.000 description 1
- 108010061982 DNA Ligases Proteins 0.000 description 1
- 238000001712 DNA sequencing Methods 0.000 description 1
- 102100020740 Dolichol phosphate-mannose biosynthesis regulatory protein 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
- 241000196324 Embryophyta Species 0.000 description 1
- 101100054935 Emericella nidulans (strain FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139) alcC gene Proteins 0.000 description 1
- 108010042407 Endonucleases Proteins 0.000 description 1
- 102000004533 Endonucleases Human genes 0.000 description 1
- 102000003951 Erythropoietin Human genes 0.000 description 1
- 108090000394 Erythropoietin Proteins 0.000 description 1
- 101710098247 Exoglucanase 1 Proteins 0.000 description 1
- 241000197417 Exomis Species 0.000 description 1
- 101150021185 FGF gene Proteins 0.000 description 1
- 102000001690 Factor VIII Human genes 0.000 description 1
- 108010054218 Factor VIII Proteins 0.000 description 1
- 102000016359 Fibronectins Human genes 0.000 description 1
- 108010067306 Fibronectins Proteins 0.000 description 1
- 229920001917 Ficoll Polymers 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
- 241000223218 Fusarium Species 0.000 description 1
- 108010073178 Glucan 1,4-alpha-Glucosidase Proteins 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
- 239000004471 Glycine Substances 0.000 description 1
- 102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 description 1
- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 description 1
- 102000004457 Granulocyte-Macrophage Colony-Stimulating Factor Human genes 0.000 description 1
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
- 108010051696 Growth Hormone Proteins 0.000 description 1
- 101710128747 Hemoglobin subunit alpha-A Proteins 0.000 description 1
- 102100021519 Hemoglobin subunit beta Human genes 0.000 description 1
- 108091005904 Hemoglobin subunit beta Proteins 0.000 description 1
- 101000932183 Homo sapiens Dolichol phosphate-mannose biosynthesis regulatory protein Proteins 0.000 description 1
- 101000987586 Homo sapiens Eosinophil peroxidase Proteins 0.000 description 1
- 101000746373 Homo sapiens Granulocyte-macrophage colony-stimulating factor Proteins 0.000 description 1
- 101000801481 Homo sapiens Tissue-type plasminogen activator Proteins 0.000 description 1
- 101000610640 Homo sapiens U4/U6 small nuclear ribonucleoprotein Prp3 Proteins 0.000 description 1
- 102000008100 Human Serum Albumin Human genes 0.000 description 1
- 108091006905 Human Serum Albumin Proteins 0.000 description 1
- XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 description 1
- 102100023915 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 108010050904 Interferons Proteins 0.000 description 1
- 102000015696 Interleukins Human genes 0.000 description 1
- 108010063738 Interleukins Proteins 0.000 description 1
- 108090000769 Isomerases Proteins 0.000 description 1
- 102000004195 Isomerases Human genes 0.000 description 1
- 241000235651 Lachancea waltii Species 0.000 description 1
- 108010059881 Lactase Proteins 0.000 description 1
- 102000004882 Lipase Human genes 0.000 description 1
- 239000004367 Lipase Substances 0.000 description 1
- 108090001060 Lipase Proteins 0.000 description 1
- 102000008072 Lymphokines Human genes 0.000 description 1
- 108010074338 Lymphokines Proteins 0.000 description 1
- 108010046938 Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
- 102000007651 Macrophage Colony-Stimulating Factor Human genes 0.000 description 1
- 229920000057 Mannan Polymers 0.000 description 1
- 108010031099 Mannose Receptor Proteins 0.000 description 1
- 241000235395 Mucor Species 0.000 description 1
- 241000221960 Neurospora Species 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 239000001888 Peptone Substances 0.000 description 1
- 108010080698 Peptones Proteins 0.000 description 1
- 102000003992 Peroxidases Human genes 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 241000276498 Pollachius virens Species 0.000 description 1
- 241000590419 Polygonia interrogationis Species 0.000 description 1
- 239000004365 Protease Substances 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
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
- 101001110823 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) 60S ribosomal protein L6-A Proteins 0.000 description 1
- 101000712176 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) 60S ribosomal protein L6-B Proteins 0.000 description 1
- 241000235346 Schizosaccharomyces Species 0.000 description 1
- 102100038803 Somatotropin Human genes 0.000 description 1
- UQZIYBXSHAGNOE-USOSMYMVSA-N Stachyose 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[C@@H]2[C@@H](O)[C@@H](O)[C@@H](O)[C@H](CO)O2)O1 UQZIYBXSHAGNOE-USOSMYMVSA-N 0.000 description 1
- 241000187747 Streptomyces Species 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 102000019197 Superoxide Dismutase Human genes 0.000 description 1
- 108010012715 Superoxide dismutase Proteins 0.000 description 1
- 241001664469 Tibicina haematodes Species 0.000 description 1
- 102000004357 Transferases Human genes 0.000 description 1
- 108090000992 Transferases Proteins 0.000 description 1
- 241000223259 Trichoderma Species 0.000 description 1
- 102100040374 U4/U6 small nuclear ribonucleoprotein Prp3 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
- GYBNOAFGEKAZTA-QOLULZROSA-N [(6z,10e,14e)-3,7,11,15,19-pentamethylicosa-6,10,14,18-tetraenyl] dihydrogen phosphate Chemical compound OP(=O)(O)OCCC(C)CC\C=C(\C)CC\C=C(/C)CC\C=C(/C)CCC=C(C)C GYBNOAFGEKAZTA-QOLULZROSA-N 0.000 description 1
- 108010048241 acetamidase Proteins 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 102000015395 alpha 1-Antitrypsin Human genes 0.000 description 1
- 108010050122 alpha 1-Antitrypsin Proteins 0.000 description 1
- 229940024142 alpha 1-antitrypsin Drugs 0.000 description 1
- SOIFLUNRINLCBN-UHFFFAOYSA-N ammonium thiocyanate Chemical compound [NH4+].[S-]C#N SOIFLUNRINLCBN-UHFFFAOYSA-N 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
- 235000019418 amylase Nutrition 0.000 description 1
- 229940025131 amylases Drugs 0.000 description 1
- 230000003698 anagen phase Effects 0.000 description 1
- 210000004102 animal cell Anatomy 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000002238 attenuated effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 108010005774 beta-Galactosidase Proteins 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 239000003914 blood derivative Substances 0.000 description 1
- 229950001336 bromamide 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
- 238000010804 cDNA synthesis Methods 0.000 description 1
- 229940041514 candida albicans extract Drugs 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000007248 cellular mechanism Effects 0.000 description 1
- 239000013043 chemical agent Substances 0.000 description 1
- 239000013611 chromosomal DNA Substances 0.000 description 1
- 230000002759 chromosomal effect Effects 0.000 description 1
- 229940080701 chymosin Drugs 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000000593 degrading effect Effects 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 210000002472 endoplasmic reticulum Anatomy 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 229940105423 erythropoietin Drugs 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 108010052305 exodeoxyribonuclease III Proteins 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 229960000301 factor viii Drugs 0.000 description 1
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 1
- 230000002414 glycolytic effect Effects 0.000 description 1
- 239000000122 growth hormone Substances 0.000 description 1
- PJJJBBJSCAKJQF-UHFFFAOYSA-N guanidinium chloride Chemical compound [Cl-].NC(N)=[NH2+] PJJJBBJSCAKJQF-UHFFFAOYSA-N 0.000 description 1
- 238000003505 heat denaturation Methods 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 208000002672 hepatitis B Diseases 0.000 description 1
- 102000046157 human CSF2 Human genes 0.000 description 1
- 102000044890 human EPO Human genes 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 238000009655 industrial fermentation Methods 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 239000000138 intercalating agent Substances 0.000 description 1
- 229940047124 interferons Drugs 0.000 description 1
- 229940047122 interleukins Drugs 0.000 description 1
- 238000011005 laboratory method Methods 0.000 description 1
- 235000019421 lipase Nutrition 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 1
- 230000000394 mitotic effect Effects 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 238000002703 mutagenesis Methods 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- GNOLWGAJQVLBSM-UHFFFAOYSA-N n,n,5,7-tetramethyl-1,2,3,4-tetrahydronaphthalen-1-amine Chemical compound C1=C(C)C=C2C(N(C)C)CCCC2=C1C GNOLWGAJQVLBSM-UHFFFAOYSA-N 0.000 description 1
- 235000019319 peptone Nutrition 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 229920001467 poly(styrenesulfonates) Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 230000001323 posttranslational effect Effects 0.000 description 1
- OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 210000001938 protoplast Anatomy 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
- 238000010188 recombinant method Methods 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000006152 selective media Substances 0.000 description 1
- 238000011451 sequencing strategy Methods 0.000 description 1
- 239000002195 soluble material Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- UQZIYBXSHAGNOE-XNSRJBNMSA-N stachyose 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[C@@H]3[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O3)O)O2)O)O1 UQZIYBXSHAGNOE-XNSRJBNMSA-N 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 239000001226 triphosphate Substances 0.000 description 1
- 235000011178 triphosphate Nutrition 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 210000005253 yeast cell Anatomy 0.000 description 1
- 239000012138 yeast extract 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
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/10—Transferases (2.)
- C12N9/1048—Glycosyltransferases (2.4)
- C12N9/1051—Hexosyltransferases (2.4.1)
-
- 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
- C12N15/80—Vectors or expression systems specially adapted for eukaryotic hosts for fungi
-
- 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
- C12N15/80—Vectors or expression systems specially adapted for eukaryotic hosts for fungi
- C12N15/81—Vectors or expression systems specially adapted for eukaryotic hosts for fungi for yeasts
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Zoology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Wood Science & Technology (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Plant Pathology (AREA)
- Physics & Mathematics (AREA)
- Biophysics (AREA)
- Medicinal Chemistry (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE4226971A DE4226971C2 (de) | 1992-08-14 | 1992-08-14 | Modifizierte Pilzzellen und Verfahren zur Herstellung rekombinanter Produkte |
| PCT/EP1993/002179 WO1994004687A1 (en) | 1992-08-14 | 1993-08-16 | Modified fungal cells and method for producing recombinant products |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO950534D0 NO950534D0 (no) | 1995-02-13 |
| NO950534L NO950534L (no) | 1995-04-05 |
| NO320349B1 true NO320349B1 (no) | 2005-11-28 |
Family
ID=6465579
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO19950534A NO320349B1 (no) | 1992-08-14 | 1995-02-13 | Modufiserte soppceller, fremgangsmate for fremstilling av rekombinante produkter, DNA-molekyl og anvendelse av slike. |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US5714377A (ja) |
| EP (1) | EP0658203B1 (ja) |
| JP (1) | JP3630424B2 (ja) |
| AT (1) | ATE245701T1 (ja) |
| AU (1) | AU679935B2 (ja) |
| CA (1) | CA2140894C (ja) |
| DE (3) | DE4226971C2 (ja) |
| ES (1) | ES2203619T3 (ja) |
| FI (1) | FI121075B (ja) |
| NO (1) | NO320349B1 (ja) |
| NZ (1) | NZ255350A (ja) |
| WO (1) | WO1994004687A1 (ja) |
| ZA (1) | ZA935915B (ja) |
Families Citing this family (56)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2686899B1 (fr) | 1992-01-31 | 1995-09-01 | Rhone Poulenc Rorer Sa | Nouveaux polypeptides biologiquement actifs, leur preparation et compositions pharmaceutiques les contenant. |
| US5728553A (en) | 1992-09-23 | 1998-03-17 | Delta Biotechnology Limited | High purity albumin and method of producing |
| JPH08173170A (ja) * | 1994-05-25 | 1996-07-09 | Kirin Brewery Co Ltd | キャンディダ・ユティリス酵母の形質転換系、およびそれによる異種遺伝子の発現 |
| WO1996036718A1 (en) * | 1995-05-18 | 1996-11-21 | Genencor International, Inc. | Expression of glycosyltransferase in aspergillus |
| GB9526733D0 (en) * | 1995-12-30 | 1996-02-28 | Delta Biotechnology Ltd | Fusion proteins |
| GB9902000D0 (en) * | 1999-01-30 | 1999-03-17 | Delta Biotechnology Ltd | Process |
| AU2007200859A1 (en) * | 1999-01-30 | 2007-03-22 | Novozymes Delta Limited | Process |
| US20050100991A1 (en) * | 2001-04-12 | 2005-05-12 | Human Genome Sciences, Inc. | Albumin fusion proteins |
| EP2267026A1 (en) * | 2000-04-12 | 2010-12-29 | Human Genome Sciences, Inc. | Albumin fusion proteins |
| US6946134B1 (en) | 2000-04-12 | 2005-09-20 | Human Genome Sciences, Inc. | Albumin fusion proteins |
| EP1379667A2 (en) * | 2000-12-05 | 2004-01-14 | The Penn State Research Foundation | Methods and compositions for highly efficient production of heterologous proteins in yeast |
| US20060084794A1 (en) * | 2001-04-12 | 2006-04-20 | Human Genome Sciences, Inc. | Albumin fusion proteins |
| US20050054051A1 (en) * | 2001-04-12 | 2005-03-10 | Human Genome Sciences, Inc. | Albumin fusion proteins |
| US7507413B2 (en) | 2001-04-12 | 2009-03-24 | Human Genome Sciences, Inc. | Albumin fusion proteins |
| US20050244931A1 (en) * | 2001-04-12 | 2005-11-03 | Human Genome Sciences, Inc. | Albumin fusion proteins |
| CA2383556A1 (en) * | 2001-05-16 | 2002-11-16 | Pharmacia & Upjohn Company | High-efficiency assay for protein mannosyl transferases |
| US7176278B2 (en) | 2001-08-30 | 2007-02-13 | Biorexis Technology, Inc. | Modified transferrin fusion proteins |
| WO2003030821A2 (en) * | 2001-10-05 | 2003-04-17 | Human Genome Sciences, Inc. | Albumin fusion proteins |
| AU2002364587A1 (en) * | 2001-12-21 | 2003-07-30 | Human Genome Sciences, Inc. | Albumin fusion proteins |
| PT1463751E (pt) * | 2001-12-21 | 2013-08-26 | Human Genome Sciences Inc | Proteínas de fusão de albumina |
| WO2003066078A1 (en) | 2002-02-07 | 2003-08-14 | Delta Biotechnology Limited | Hiv inhibiting proteins |
| DE60322106D1 (de) * | 2002-12-20 | 2008-08-21 | Unilever Nv | Herstellung von frostschutzprotein |
| GB0329681D0 (en) | 2003-12-23 | 2004-01-28 | Delta Biotechnology Ltd | Gene expression technique |
| GB0329722D0 (en) | 2003-12-23 | 2004-01-28 | Delta Biotechnology Ltd | Modified plasmid and use thereof |
| DK2330200T3 (en) | 2004-12-23 | 2017-07-24 | Albumedix As | GENE EXPRESSION TECHNIQUE |
| AU2006316838B2 (en) | 2005-11-15 | 2012-04-12 | Glycofi, Inc | Production of glycoproteins with reduced O-glycosylation |
| AU2012203729B2 (en) * | 2005-11-22 | 2014-01-30 | Glycofi, Inc | Production of glycoproteins with reduced O-glycosylation |
| EP1816201A1 (en) * | 2006-02-06 | 2007-08-08 | CSL Behring GmbH | Modified coagulation factor VIIa with extended half-life |
| JP5131666B2 (ja) * | 2006-05-16 | 2013-01-30 | 独立行政法人産業技術総合研究所 | タンパク質の高分泌生産方法 |
| ATE524493T1 (de) | 2006-07-24 | 2011-09-15 | Biorexis Pharmaceutical Corp | Exendin-fusionsproteine |
| GB0711424D0 (en) * | 2007-06-13 | 2007-07-25 | Novozymes Delta Ltd | Recombinant transferrin mutants |
| WO2009019314A1 (en) | 2007-08-08 | 2009-02-12 | Novozymes A/S | Transferrin variants and conjugates |
| US8637435B2 (en) * | 2007-11-16 | 2014-01-28 | Merck Sharp & Dohme Corp. | Eukaryotic cell display systems |
| WO2009105357A1 (en) | 2008-02-20 | 2009-08-27 | Glycofi, Inc. | Vectors and yeast strains for protein production |
| EP2263089B1 (en) | 2008-03-03 | 2015-01-28 | GlycoFi, Inc. | Surface display of recombinant proteins in lower eukaryotes |
| EP2324121B1 (en) * | 2008-08-12 | 2012-11-07 | GlycoFi, Inc. | Improved vectors and yeast strains for protein production: ca2+ atpase overexpression |
| US9120871B2 (en) | 2009-01-23 | 2015-09-01 | Novo Nordisk A/S | Process for preparing FGF21 with low degree of O-glycosylation |
| EP2393834B1 (en) | 2009-02-06 | 2013-04-17 | Novozymes Biopharma DK A/S | Purification process |
| US9493545B2 (en) | 2009-02-11 | 2016-11-15 | Albumedix A/S | Albumin variants and conjugates |
| US20120003695A1 (en) | 2009-02-25 | 2012-01-05 | Davidson Robert C | Metabolic engineering of a galactose assimilation pathway in the glycoengineered yeast pichia pastoris |
| EP3421491A3 (en) | 2009-10-30 | 2019-03-27 | Albumedix Ltd | Albumin variants |
| JP2013509181A (ja) | 2009-10-30 | 2013-03-14 | メルク・シャープ・エンド・ドーム・コーポレイション | ジペプチジルアミノペプチダーゼ活性を欠くピチア・パストリスにおける治療用タンパク質の製造方法 |
| EP2534255B1 (en) * | 2010-02-10 | 2017-05-10 | Biocon Limited | Method of reducing glycosylation of proteins, processes and proteins thereof |
| MX2012009802A (es) | 2010-02-24 | 2012-09-12 | Merck Sharp & Dohme | Metodo para incrementar la ocupacion del sitio de n-glucosilacion en glucoproteinas terapeuticas producidas en pichia pastoris. |
| JP5969458B2 (ja) | 2010-04-09 | 2016-08-17 | アルブミディクス アクティーゼルスカブ | アルブミン誘導体及び変異体 |
| MX339809B (es) | 2010-05-27 | 2016-06-09 | Merck Sharp & Dohme Corp * | Metodo para preparar anticuerpos con propiedades mejoradas. |
| JP5885191B2 (ja) | 2011-01-04 | 2016-03-15 | 国立研究開発法人産業技術総合研究所 | 糖鎖改変酵母及びそれを用いた糖タンパク質の製造方法 |
| CN103764837A (zh) | 2011-02-25 | 2014-04-30 | 默沙东公司 | 用于生产具有修饰的o-糖基化的蛋白的酵母菌株 |
| KR20140028013A (ko) | 2011-05-25 | 2014-03-07 | 머크 샤프 앤드 돔 코포레이션 | 개선된 특성을 갖는 Fc-함유 폴리펩티드를 제조하는 방법 |
| EP2780364A2 (en) | 2011-11-18 | 2014-09-24 | Eleven Biotherapeutics, Inc. | Proteins with improved half-life and other properties |
| BR112014018679A2 (pt) | 2012-03-16 | 2017-07-04 | Novozymes Biopharma Dk As | variantes de albumina |
| BR112015010318A2 (pt) | 2012-11-08 | 2017-08-22 | Albumedix As | Variantes de albumina |
| WO2014195452A1 (en) | 2013-06-07 | 2014-12-11 | Novo Nordisk A/S | Method for making mature insulin polypeptides |
| CA2916594C (en) | 2013-07-04 | 2020-03-10 | Novartis Ag | O-mannosyltransferase deficient filamentous fungal cells and methods of use thereof |
| CA2954974A1 (en) | 2014-07-21 | 2016-01-28 | Glykos Finland Oy | Production of glycoproteins with mammalian-like n-glycans in filamentous fungi |
| CN108137674B (zh) | 2015-08-20 | 2022-12-06 | 阿尔布梅迪克斯医疗有限公司 | 白蛋白变体和缀合物 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| YU257278A (en) * | 1977-11-08 | 1984-02-29 | Genentech Inc | Process for obtaining a recombinat clone carrier |
| IT1203758B (it) * | 1986-03-27 | 1989-02-23 | Univ Roma | Vettori di clonazione e di espressione di geni eterologhi in lieviti e lieviti trasformati con tali vettori |
| US4929553A (en) * | 1987-05-29 | 1990-05-29 | Canadian Patents & Development Ltd. | Protease for specific processing of secreted proteins |
| FR2649991B2 (fr) * | 1988-08-05 | 1994-03-04 | Rhone Poulenc Sante | Utilisation de derives stables du plasmide pkd1 pour l'expression et la secretion de proteines heterologues dans les levures du genre kluyveromyces |
| FR2655660B1 (fr) * | 1989-12-11 | 1992-03-20 | Rhone Poulenc Sante | Nouveaux polypeptides, sequences d'adn permettant leur expression, procede de preparation et leur utilisation. |
-
1992
- 1992-08-14 DE DE4226971A patent/DE4226971C2/de not_active Expired - Lifetime
- 1992-08-14 DE DE4244915A patent/DE4244915C2/de not_active Expired - Lifetime
-
1993
- 1993-08-13 ZA ZA935915A patent/ZA935915B/xx unknown
- 1993-08-16 AU AU49482/93A patent/AU679935B2/en not_active Expired
- 1993-08-16 EP EP93919067A patent/EP0658203B1/en not_active Expired - Lifetime
- 1993-08-16 NZ NZ255350A patent/NZ255350A/en not_active IP Right Cessation
- 1993-08-16 US US08/381,931 patent/US5714377A/en not_active Expired - Lifetime
- 1993-08-16 WO PCT/EP1993/002179 patent/WO1994004687A1/en active IP Right Grant
- 1993-08-16 CA CA002140894A patent/CA2140894C/en not_active Expired - Lifetime
- 1993-08-16 DE DE69333112T patent/DE69333112T2/de not_active Expired - Lifetime
- 1993-08-16 JP JP50589294A patent/JP3630424B2/ja not_active Expired - Lifetime
- 1993-08-16 ES ES93919067T patent/ES2203619T3/es not_active Expired - Lifetime
- 1993-08-16 AT AT93919067T patent/ATE245701T1/de active
-
1995
- 1995-02-13 FI FI950628A patent/FI121075B/fi not_active IP Right Cessation
- 1995-02-13 NO NO19950534A patent/NO320349B1/no not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| US5714377A (en) | 1998-02-03 |
| DE4226971C2 (de) | 1997-01-16 |
| EP0658203A1 (en) | 1995-06-21 |
| FI121075B (fi) | 2010-06-30 |
| JP3630424B2 (ja) | 2005-03-16 |
| NO950534D0 (no) | 1995-02-13 |
| EP0658203B1 (en) | 2003-07-23 |
| DE4226971A1 (de) | 1994-02-17 |
| FI950628A (fi) | 1995-02-13 |
| AU679935B2 (en) | 1997-07-17 |
| CA2140894A1 (en) | 1994-03-03 |
| ZA935915B (en) | 1995-04-13 |
| DE69333112D1 (de) | 2003-08-28 |
| AU4948293A (en) | 1994-03-15 |
| NO950534L (no) | 1995-04-05 |
| ATE245701T1 (de) | 2003-08-15 |
| DE4244915C2 (de) | 1998-12-03 |
| DE69333112T2 (de) | 2004-06-09 |
| CA2140894C (en) | 2010-03-02 |
| JPH08500975A (ja) | 1996-02-06 |
| FI950628A0 (fi) | 1995-02-13 |
| NZ255350A (en) | 1996-11-26 |
| WO1994004687A1 (en) | 1994-03-03 |
| ES2203619T3 (es) | 2004-04-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| NO320349B1 (no) | Modufiserte soppceller, fremgangsmate for fremstilling av rekombinante produkter, DNA-molekyl og anvendelse av slike. | |
| KR101262682B1 (ko) | 유전자 발현 기술 | |
| USRE37767E1 (en) | Highly stable recombinant yeasts for the production of recombinant proteins | |
| CA2551496C (en) | 2-micron family plasmid and use thereof | |
| JAUNIAUX et al. | GAP1, the general amino acid permease gene of Saccharomyces cerevisiae: nucleotide sequence, protein similarity with the other bakers yeast amino acid permeases, and nitrogen catabolite repression | |
| Mireau et al. | The same Arabidopsis gene encodes both cytosolic and mitochondrial alanyl-tRNA synthetases. | |
| NO180381B (no) | DNA-konstruksjoner inneholdende en Kluyveromyces alfa-faktor ledersekvens for utskillelse av heterologe polypeptider, ekspresjonsvektor og fremgangsmåte til fremstilling av et heterologt polypeptid i gjær | |
| Fellinger et al. | Expression of the α‐galactosidase from Cyamopsis tetragonoloba (guar) by Hansenula polymorpha | |
| US20240209328A1 (en) | Protein compositions and methods of production | |
| San Segundo et al. | SSG1, a gene encoding a sporulation-specific 1, 3-beta-glucanase in Saccharomyces cerevisiae | |
| EP0631627A1 (en) | A method for production of proteins in yeast | |
| WO2006107084A1 (ja) | 分泌型耐熱性酵素を高分泌生産できる酵母変異株 | |
| EP4186976A1 (en) | N-glycosylation mutant rice, method for preparing same, and method for preparing rice for protein production by using same | |
| CN113549560B (zh) | 一种用于糖蛋白制备的工程化酵母构建方法及其菌株 | |
| Katsukawa et al. | A recQ gene homolog from the basidiomycetous mushroom Lentinula edodes: sequence analysis and expression | |
| Yoshida et al. | Schizosaccharomyces pombe stt3+ is a functional homologue of Saccharomyces cerevisiae STT3 which regulates oligosaccharyltransferase activity | |
| Kanai | STUDIES ON ISOCITRATE LYASE GENE PROMOTER OF | |
| Kanai | STUDIES ON ISOCITRATE LYASE GENE PROMOTER OF CANDIDA TROPICALIS: ITS REGULATION AND APPLICATION TO HETEROLOGOUS GENE EXPRESSION | |
| Boer et al. | The MAPk ASTE11 is involved in the maintenance of cell wall integrity and in¢ lamentation in Arxula adeninivorans, but not in adaptation to hypertonic stress |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MK1K | Patent expired |