KR20050000558A - 인간 항체를 제조할 수 있는 트랜스제닉 유제동물 - Google Patents
인간 항체를 제조할 수 있는 트랜스제닉 유제동물 Download PDFInfo
- Publication number
- KR20050000558A KR20050000558A KR10-2004-7018599A KR20047018599A KR20050000558A KR 20050000558 A KR20050000558 A KR 20050000558A KR 20047018599 A KR20047018599 A KR 20047018599A KR 20050000558 A KR20050000558 A KR 20050000558A
- Authority
- KR
- South Korea
- Prior art keywords
- embryo
- cells
- cell
- ungulate
- oocytes
- Prior art date
- 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.)
- Ceased
Links
- 241000282414 Homo sapiens Species 0.000 title claims abstract description 283
- 230000009261 transgenic effect Effects 0.000 title claims description 95
- 230000016784 immunoglobulin production Effects 0.000 title description 4
- 238000000034 method Methods 0.000 claims abstract description 238
- 241000283690 Bos taurus Species 0.000 claims abstract description 208
- 230000014509 gene expression Effects 0.000 claims abstract description 95
- 238000004519 manufacturing process Methods 0.000 claims abstract description 34
- 210000004027 cell Anatomy 0.000 claims description 664
- 210000001161 mammalian embryo Anatomy 0.000 claims description 290
- 210000003754 fetus Anatomy 0.000 claims description 224
- 210000002257 embryonic structure Anatomy 0.000 claims description 219
- 210000004940 nucleus Anatomy 0.000 claims description 200
- 210000000287 oocyte Anatomy 0.000 claims description 198
- 108090000623 proteins and genes Proteins 0.000 claims description 193
- 150000007523 nucleic acids Chemical class 0.000 claims description 192
- 102000039446 nucleic acids Human genes 0.000 claims description 177
- 108020004707 nucleic acids Proteins 0.000 claims description 177
- 108010077544 Chromatin Proteins 0.000 claims description 149
- 210000003483 chromatin Anatomy 0.000 claims description 149
- 238000012546 transfer Methods 0.000 claims description 104
- 210000000349 chromosome Anatomy 0.000 claims description 103
- 230000008672 reprogramming Effects 0.000 claims description 101
- 102000004169 proteins and genes Human genes 0.000 claims description 89
- 210000002950 fibroblast Anatomy 0.000 claims description 87
- 239000000284 extract Substances 0.000 claims description 86
- 230000001605 fetal effect Effects 0.000 claims description 85
- 210000003719 b-lymphocyte Anatomy 0.000 claims description 76
- 230000035772 mutation Effects 0.000 claims description 69
- 241001465754 Metazoa Species 0.000 claims description 57
- 108060003951 Immunoglobulin Proteins 0.000 claims description 55
- 102000018358 immunoglobulin Human genes 0.000 claims description 55
- 239000012634 fragment Substances 0.000 claims description 48
- 230000008707 rearrangement Effects 0.000 claims description 47
- 108700005091 Immunoglobulin Genes Proteins 0.000 claims description 44
- 239000000427 antigen Substances 0.000 claims description 41
- 108091007433 antigens Proteins 0.000 claims description 41
- 102000036639 antigens Human genes 0.000 claims description 41
- 238000000338 in vitro Methods 0.000 claims description 39
- 230000000394 mitotic effect Effects 0.000 claims description 38
- 241000894007 species Species 0.000 claims description 38
- 230000018109 developmental process Effects 0.000 claims description 33
- 238000011161 development Methods 0.000 claims description 32
- 239000000243 solution Substances 0.000 claims description 25
- 239000003550 marker Substances 0.000 claims description 23
- 210000002966 serum Anatomy 0.000 claims description 23
- 230000015572 biosynthetic process Effects 0.000 claims description 22
- 230000002759 chromosomal effect Effects 0.000 claims description 22
- 239000003599 detergent Substances 0.000 claims description 22
- 230000005030 transcription termination Effects 0.000 claims description 22
- 230000004927 fusion Effects 0.000 claims description 21
- 239000012528 membrane Substances 0.000 claims description 21
- 210000001082 somatic cell Anatomy 0.000 claims description 20
- 210000004291 uterus Anatomy 0.000 claims description 20
- 210000004602 germ cell Anatomy 0.000 claims description 18
- 108700028369 Alleles Proteins 0.000 claims description 17
- 238000011534 incubation Methods 0.000 claims description 17
- 230000002829 reductive effect Effects 0.000 claims description 17
- 108020004999 messenger RNA Proteins 0.000 claims description 16
- 210000000170 cell membrane Anatomy 0.000 claims description 15
- 235000013336 milk Nutrition 0.000 claims description 15
- 239000008267 milk Substances 0.000 claims description 15
- 210000004080 milk Anatomy 0.000 claims description 15
- 230000003115 biocidal effect Effects 0.000 claims description 14
- 230000004543 DNA replication Effects 0.000 claims description 12
- 241001494479 Pecora Species 0.000 claims description 12
- 102000001253 Protein Kinase Human genes 0.000 claims description 11
- 230000032823 cell division Effects 0.000 claims description 11
- 108060006633 protein kinase Proteins 0.000 claims description 11
- 241000283707 Capra Species 0.000 claims description 10
- 108020004705 Codon Proteins 0.000 claims description 10
- 230000001413 cellular effect Effects 0.000 claims description 10
- 239000000839 emulsion Substances 0.000 claims description 10
- 239000012266 salt solution Substances 0.000 claims description 10
- 241000282898 Sus scrofa Species 0.000 claims description 8
- 108700019146 Transgenes Proteins 0.000 claims description 5
- 210000002308 embryonic cell Anatomy 0.000 claims description 5
- 210000004408 hybridoma Anatomy 0.000 claims description 5
- 210000001671 embryonic stem cell Anatomy 0.000 claims description 4
- 230000001939 inductive effect Effects 0.000 claims description 4
- 230000000977 initiatory effect Effects 0.000 claims description 4
- 230000003169 placental effect Effects 0.000 claims description 4
- 210000003969 blast cell Anatomy 0.000 claims description 3
- 210000001612 chondrocyte Anatomy 0.000 claims description 3
- 210000001339 epidermal cell Anatomy 0.000 claims description 3
- 210000002919 epithelial cell Anatomy 0.000 claims description 3
- 210000003743 erythrocyte Anatomy 0.000 claims description 3
- 239000000835 fiber Substances 0.000 claims description 3
- 210000003958 hematopoietic stem cell Anatomy 0.000 claims description 3
- 210000002510 keratinocyte Anatomy 0.000 claims description 3
- 210000002540 macrophage Anatomy 0.000 claims description 3
- 210000002752 melanocyte Anatomy 0.000 claims description 3
- 210000001616 monocyte Anatomy 0.000 claims description 3
- 210000000663 muscle cell Anatomy 0.000 claims description 3
- 210000002569 neuron Anatomy 0.000 claims description 3
- 210000002826 placenta Anatomy 0.000 claims description 3
- 206010035226 Plasma cell myeloma Diseases 0.000 claims description 2
- 201000000050 myeloid neoplasm Diseases 0.000 claims description 2
- 239000003242 anti bacterial agent Substances 0.000 claims 1
- 210000004507 artificial chromosome Anatomy 0.000 abstract description 13
- 230000002779 inactivation Effects 0.000 abstract description 5
- 210000000688 human artificial chromosome Anatomy 0.000 description 96
- 239000002609 medium Substances 0.000 description 69
- 235000018102 proteins Nutrition 0.000 description 67
- 108020004414 DNA Proteins 0.000 description 62
- YPHMISFOHDHNIV-FSZOTQKASA-N cycloheximide Chemical compound C1[C@@H](C)C[C@H](C)C(=O)[C@@H]1[C@H](O)CC1CC(=O)NC(=O)C1 YPHMISFOHDHNIV-FSZOTQKASA-N 0.000 description 60
- 239000013615 primer Substances 0.000 description 56
- 244000309466 calf Species 0.000 description 55
- 241000124008 Mammalia Species 0.000 description 52
- 101000890594 Homo sapiens A-kinase anchor protein 8 Proteins 0.000 description 49
- 102100040086 A-kinase anchor protein 8 Human genes 0.000 description 48
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 39
- 239000000872 buffer Substances 0.000 description 37
- 108010025821 lamin C Proteins 0.000 description 37
- 210000000952 spleen Anatomy 0.000 description 35
- 210000000633 nuclear envelope Anatomy 0.000 description 34
- 238000003757 reverse transcription PCR Methods 0.000 description 34
- 238000010367 cloning Methods 0.000 description 30
- 239000013598 vector Substances 0.000 description 29
- 238000004458 analytical method Methods 0.000 description 28
- 239000000203 mixture Substances 0.000 description 28
- 210000005053 lamin Anatomy 0.000 description 27
- 210000001519 tissue Anatomy 0.000 description 26
- 238000003780 insertion Methods 0.000 description 25
- 230000037431 insertion Effects 0.000 description 25
- 230000000694 effects Effects 0.000 description 24
- 239000002299 complementary DNA Substances 0.000 description 22
- 238000003752 polymerase chain reaction Methods 0.000 description 22
- 230000000392 somatic effect Effects 0.000 description 22
- 102000006835 Lamins Human genes 0.000 description 21
- 108010047294 Lamins Proteins 0.000 description 21
- 239000000047 product Substances 0.000 description 21
- 239000011780 sodium chloride Substances 0.000 description 20
- 230000000875 corresponding effect Effects 0.000 description 19
- 210000004185 liver Anatomy 0.000 description 19
- 210000004379 membrane Anatomy 0.000 description 19
- 239000011541 reaction mixture Substances 0.000 description 19
- 101710156592 Putative TATA-binding protein pB263R Proteins 0.000 description 18
- 102100040296 TATA-box-binding protein Human genes 0.000 description 18
- 101710145783 TATA-box-binding protein Proteins 0.000 description 18
- RJURFGZVJUQBHK-UHFFFAOYSA-N actinomycin D Natural products CC1OC(=O)C(C(C)C)N(C)C(=O)CN(C)C(=O)C2CCCN2C(=O)C(C(C)C)NC(=O)C1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)NC4C(=O)NC(C(N5CCCC5C(=O)N(C)CC(=O)N(C)C(C(C)C)C(=O)OC4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-UHFFFAOYSA-N 0.000 description 18
- 108010021099 Lamin Type A Proteins 0.000 description 17
- 239000002773 nucleotide Substances 0.000 description 17
- 125000003729 nucleotide group Chemical group 0.000 description 17
- 102000008201 Lamin Type A Human genes 0.000 description 16
- 239000003153 chemical reaction reagent Substances 0.000 description 16
- 239000002953 phosphate buffered saline Substances 0.000 description 16
- 238000002360 preparation method Methods 0.000 description 16
- 239000000523 sample Substances 0.000 description 16
- 241000699666 Mus <mouse, genus> Species 0.000 description 15
- 230000004913 activation Effects 0.000 description 15
- 238000001994 activation Methods 0.000 description 15
- 239000011543 agarose gel Substances 0.000 description 15
- 230000003321 amplification Effects 0.000 description 15
- 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 15
- 238000003199 nucleic acid amplification method Methods 0.000 description 15
- 230000035935 pregnancy Effects 0.000 description 15
- 238000010561 standard procedure Methods 0.000 description 15
- 230000035897 transcription Effects 0.000 description 15
- 238000013518 transcription Methods 0.000 description 15
- 210000004556 brain Anatomy 0.000 description 14
- 210000003917 human chromosome Anatomy 0.000 description 14
- 239000006228 supernatant Substances 0.000 description 14
- 102100031181 Glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 13
- 238000010240 RT-PCR analysis Methods 0.000 description 13
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 13
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 12
- 241000699670 Mus sp. Species 0.000 description 12
- 239000013504 Triton X-100 Substances 0.000 description 12
- 229920004890 Triton X-100 Polymers 0.000 description 12
- 230000010428 chromatin condensation Effects 0.000 description 12
- 150000001875 compounds Chemical class 0.000 description 12
- 238000001514 detection method Methods 0.000 description 12
- 238000003556 assay Methods 0.000 description 11
- 210000002459 blastocyst Anatomy 0.000 description 11
- 230000005494 condensation Effects 0.000 description 11
- 238000009833 condensation Methods 0.000 description 11
- -1 digitotonin Substances 0.000 description 11
- 235000013601 eggs Nutrition 0.000 description 11
- 239000001963 growth medium Substances 0.000 description 11
- 102000040945 Transcription factor Human genes 0.000 description 10
- 108091023040 Transcription factor Proteins 0.000 description 10
- 150000001413 amino acids Chemical group 0.000 description 10
- 238000006243 chemical reaction Methods 0.000 description 10
- 238000010166 immunofluorescence Methods 0.000 description 10
- 210000005059 placental tissue Anatomy 0.000 description 10
- 239000013641 positive control Substances 0.000 description 10
- 238000007634 remodeling Methods 0.000 description 10
- 108010092160 Dactinomycin Proteins 0.000 description 9
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
- RJURFGZVJUQBHK-IIXSONLDSA-N actinomycin D Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)N[C@@H]4C(=O)N[C@@H](C(N5CCC[C@H]5C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-IIXSONLDSA-N 0.000 description 9
- 230000027455 binding Effects 0.000 description 9
- 210000004369 blood Anatomy 0.000 description 9
- 239000008280 blood Substances 0.000 description 9
- 238000005119 centrifugation Methods 0.000 description 9
- 210000000805 cytoplasm Anatomy 0.000 description 9
- 229960000640 dactinomycin Drugs 0.000 description 9
- 238000002347 injection Methods 0.000 description 9
- 239000007924 injection Substances 0.000 description 9
- 102000040430 polynucleotide Human genes 0.000 description 9
- 108091033319 polynucleotide Proteins 0.000 description 9
- 239000002157 polynucleotide Substances 0.000 description 9
- 238000000746 purification Methods 0.000 description 9
- 101000840258 Homo sapiens Immunoglobulin J chain Proteins 0.000 description 8
- 102100029571 Immunoglobulin J chain Human genes 0.000 description 8
- 238000002474 experimental method Methods 0.000 description 8
- 230000004720 fertilization Effects 0.000 description 8
- 239000000499 gel Substances 0.000 description 8
- 210000000987 immune system Anatomy 0.000 description 8
- 230000003053 immunization Effects 0.000 description 8
- 239000003112 inhibitor Substances 0.000 description 8
- 230000014759 maintenance of location Effects 0.000 description 8
- 230000008774 maternal effect Effects 0.000 description 8
- 239000013642 negative control Substances 0.000 description 8
- 239000008188 pellet Substances 0.000 description 8
- 239000012071 phase Substances 0.000 description 8
- 238000011282 treatment Methods 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 102000000905 Cadherin Human genes 0.000 description 7
- 108050007957 Cadherin Proteins 0.000 description 7
- 241000282412 Homo Species 0.000 description 7
- 102000008297 Nuclear Matrix-Associated Proteins Human genes 0.000 description 7
- 108010035916 Nuclear Matrix-Associated Proteins Proteins 0.000 description 7
- 102000035195 Peptidases Human genes 0.000 description 7
- 108091005804 Peptidases Proteins 0.000 description 7
- 239000004365 Protease Substances 0.000 description 7
- 238000010494 dissociation reaction Methods 0.000 description 7
- 230000005593 dissociations Effects 0.000 description 7
- 238000009826 distribution Methods 0.000 description 7
- 239000012091 fetal bovine serum Substances 0.000 description 7
- 238000002649 immunization Methods 0.000 description 7
- 229940072221 immunoglobulins Drugs 0.000 description 7
- 230000001976 improved effect Effects 0.000 description 7
- 230000004044 response Effects 0.000 description 7
- 230000002441 reversible effect Effects 0.000 description 7
- 238000010186 staining Methods 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- 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 6
- 102000009728 CDC2 Protein Kinase Human genes 0.000 description 6
- 108010034798 CDC2 Protein Kinase Proteins 0.000 description 6
- 102000008130 Cyclic AMP-Dependent Protein Kinases Human genes 0.000 description 6
- 108010049894 Cyclic AMP-Dependent Protein Kinases Proteins 0.000 description 6
- 102000004127 Cytokines Human genes 0.000 description 6
- 108090000695 Cytokines Proteins 0.000 description 6
- 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 6
- 102100036961 Nuclear mitotic apparatus protein 1 Human genes 0.000 description 6
- 101710104794 Nuclear mitotic apparatus protein 1 Proteins 0.000 description 6
- 229930040373 Paraformaldehyde Natural products 0.000 description 6
- 108091000080 Phosphotransferase Proteins 0.000 description 6
- 238000004873 anchoring Methods 0.000 description 6
- 239000006059 cover glass Substances 0.000 description 6
- 230000001086 cytosolic effect Effects 0.000 description 6
- 230000007812 deficiency Effects 0.000 description 6
- 238000010185 immunofluorescence analysis Methods 0.000 description 6
- 230000016507 interphase Effects 0.000 description 6
- 229920002866 paraformaldehyde Polymers 0.000 description 6
- 210000005105 peripheral blood lymphocyte Anatomy 0.000 description 6
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 6
- 238000006366 phosphorylation reaction Methods 0.000 description 6
- 102000020233 phosphotransferase Human genes 0.000 description 6
- RXWNCPJZOCPEPQ-NVWDDTSBSA-N puromycin Chemical compound C1=CC(OC)=CC=C1C[C@H](N)C(=O)N[C@H]1[C@@H](O)[C@H](N2C3=NC=NC(=C3N=C2)N(C)C)O[C@@H]1CO RXWNCPJZOCPEPQ-NVWDDTSBSA-N 0.000 description 6
- 102000005962 receptors Human genes 0.000 description 6
- 108020003175 receptors Proteins 0.000 description 6
- 150000003839 salts Chemical class 0.000 description 6
- 230000001225 therapeutic effect Effects 0.000 description 6
- 230000035899 viability Effects 0.000 description 6
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 5
- 239000007995 HEPES buffer Substances 0.000 description 5
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 5
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 5
- 108091028043 Nucleic acid sequence Proteins 0.000 description 5
- 229920001213 Polysorbate 20 Polymers 0.000 description 5
- 102000029797 Prion Human genes 0.000 description 5
- 108091000054 Prion Proteins 0.000 description 5
- 108010007568 Protamines Proteins 0.000 description 5
- 102000007327 Protamines Human genes 0.000 description 5
- 102000003923 Protein Kinase C Human genes 0.000 description 5
- 108090000315 Protein Kinase C Proteins 0.000 description 5
- 229930006000 Sucrose Natural products 0.000 description 5
- 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 5
- 108090000631 Trypsin Proteins 0.000 description 5
- 102000004142 Trypsin Human genes 0.000 description 5
- 239000011575 calcium Substances 0.000 description 5
- 239000003710 calcium ionophore Substances 0.000 description 5
- 229910052799 carbon Inorganic materials 0.000 description 5
- 230000007423 decrease Effects 0.000 description 5
- 238000012217 deletion Methods 0.000 description 5
- 230000037430 deletion Effects 0.000 description 5
- 238000000605 extraction Methods 0.000 description 5
- 238000003119 immunoblot Methods 0.000 description 5
- 230000001965 increasing effect Effects 0.000 description 5
- 230000035800 maturation Effects 0.000 description 5
- 230000001404 mediated effect Effects 0.000 description 5
- 230000004048 modification Effects 0.000 description 5
- 238000012986 modification Methods 0.000 description 5
- 210000000299 nuclear matrix Anatomy 0.000 description 5
- 230000026731 phosphorylation Effects 0.000 description 5
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 5
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- 108090000765 processed proteins & peptides Proteins 0.000 description 5
- 230000009257 reactivity Effects 0.000 description 5
- 238000012163 sequencing technique Methods 0.000 description 5
- 210000000130 stem cell Anatomy 0.000 description 5
- 239000005720 sucrose Substances 0.000 description 5
- 230000004083 survival effect Effects 0.000 description 5
- 230000001360 synchronised effect Effects 0.000 description 5
- 230000008685 targeting Effects 0.000 description 5
- 230000014616 translation Effects 0.000 description 5
- 239000012588 trypsin Substances 0.000 description 5
- 238000001262 western blot Methods 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 101150097493 D gene Proteins 0.000 description 4
- 241000702421 Dependoparvovirus Species 0.000 description 4
- 241000283073 Equus caballus Species 0.000 description 4
- 102000011787 Histone Methyltransferases Human genes 0.000 description 4
- 108010036115 Histone Methyltransferases Proteins 0.000 description 4
- 101150008942 J gene Proteins 0.000 description 4
- 108010021101 Lamin Type B Proteins 0.000 description 4
- DRBBFCLWYRJSJZ-UHFFFAOYSA-N N-phosphocreatine Chemical compound OC(=O)CN(C)C(=N)NP(O)(O)=O DRBBFCLWYRJSJZ-UHFFFAOYSA-N 0.000 description 4
- 241000283973 Oryctolagus cuniculus Species 0.000 description 4
- 210000001744 T-lymphocyte Anatomy 0.000 description 4
- 101150117115 V gene Proteins 0.000 description 4
- 239000012190 activator Substances 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- 230000001588 bifunctional effect Effects 0.000 description 4
- 230000008859 change Effects 0.000 description 4
- 210000003022 colostrum Anatomy 0.000 description 4
- 235000021277 colostrum Nutrition 0.000 description 4
- 230000006378 damage Effects 0.000 description 4
- 238000002716 delivery method Methods 0.000 description 4
- 238000004925 denaturation Methods 0.000 description 4
- 230000036425 denaturation Effects 0.000 description 4
- 238000010790 dilution Methods 0.000 description 4
- 239000012895 dilution Substances 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 239000000975 dye Substances 0.000 description 4
- 239000011521 glass Substances 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 238000011065 in-situ storage Methods 0.000 description 4
- 238000002372 labelling Methods 0.000 description 4
- 210000000265 leukocyte Anatomy 0.000 description 4
- 239000006166 lysate Substances 0.000 description 4
- 210000003794 male germ cell Anatomy 0.000 description 4
- 238000010449 nuclear transplantation Methods 0.000 description 4
- 229920000729 poly(L-lysine) polymer Polymers 0.000 description 4
- 229940048914 protamine Drugs 0.000 description 4
- 235000019419 proteases Nutrition 0.000 description 4
- 230000000717 retained effect Effects 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 238000000527 sonication Methods 0.000 description 4
- 239000012536 storage buffer Substances 0.000 description 4
- 239000000758 substrate Substances 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 239000003053 toxin Substances 0.000 description 4
- 231100000765 toxin Toxicity 0.000 description 4
- 108700012359 toxins Proteins 0.000 description 4
- 238000002054 transplantation Methods 0.000 description 4
- 239000003656 tris buffered saline Substances 0.000 description 4
- 239000013603 viral vector Substances 0.000 description 4
- 230000002407 ATP formation Effects 0.000 description 3
- 108010039627 Aprotinin Proteins 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 3
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
- 102000005403 Casein Kinases Human genes 0.000 description 3
- 108010031425 Casein Kinases Proteins 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 3
- 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 3
- 238000002965 ELISA Methods 0.000 description 3
- 108700039887 Essential Genes Proteins 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 108700024394 Exon Proteins 0.000 description 3
- 108010033040 Histones Proteins 0.000 description 3
- 102000006947 Histones Human genes 0.000 description 3
- 108090000144 Human Proteins Proteins 0.000 description 3
- 102000003839 Human Proteins Human genes 0.000 description 3
- 102000012745 Immunoglobulin Subunits Human genes 0.000 description 3
- 108010079585 Immunoglobulin Subunits Proteins 0.000 description 3
- 102000043136 MAP kinase family Human genes 0.000 description 3
- 108091054455 MAP kinase family Proteins 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 206010028980 Neoplasm Diseases 0.000 description 3
- 238000010222 PCR analysis Methods 0.000 description 3
- 229940123573 Protein synthesis inhibitor Drugs 0.000 description 3
- 229940122618 Trypsin inhibitor Drugs 0.000 description 3
- 101710162629 Trypsin inhibitor Proteins 0.000 description 3
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 3
- 241000700605 Viruses Species 0.000 description 3
- 239000002671 adjuvant Substances 0.000 description 3
- 210000004102 animal cell Anatomy 0.000 description 3
- 238000000137 annealing Methods 0.000 description 3
- 230000003497 anti-pneumococcal effect Effects 0.000 description 3
- 230000005875 antibody response Effects 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
- 229960004405 aprotinin Drugs 0.000 description 3
- 210000001109 blastomere Anatomy 0.000 description 3
- 230000007910 cell fusion Effects 0.000 description 3
- 230000006037 cell lysis Effects 0.000 description 3
- 239000008004 cell lysis buffer Substances 0.000 description 3
- 210000003855 cell nucleus Anatomy 0.000 description 3
- 239000006285 cell suspension Substances 0.000 description 3
- 238000010276 construction Methods 0.000 description 3
- 230000009089 cytolysis Effects 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- 238000010586 diagram Methods 0.000 description 3
- 230000013020 embryo development Effects 0.000 description 3
- CJAONIOAQZUHPN-KKLWWLSJSA-N ethyl 12-[[2-[(2r,3r)-3-[2-[(12-ethoxy-12-oxododecyl)-methylamino]-2-oxoethoxy]butan-2-yl]oxyacetyl]-methylamino]dodecanoate Chemical compound CCOC(=O)CCCCCCCCCCCN(C)C(=O)CO[C@H](C)[C@@H](C)OCC(=O)N(C)CCCCCCCCCCCC(=O)OCC CJAONIOAQZUHPN-KKLWWLSJSA-N 0.000 description 3
- 230000008175 fetal development Effects 0.000 description 3
- 239000012530 fluid Substances 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 102000034356 gene-regulatory proteins Human genes 0.000 description 3
- 108091006104 gene-regulatory proteins Proteins 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- 238000003306 harvesting Methods 0.000 description 3
- 238000000265 homogenisation Methods 0.000 description 3
- 238000002744 homologous recombination Methods 0.000 description 3
- 230000006801 homologous recombination Effects 0.000 description 3
- 210000005260 human cell Anatomy 0.000 description 3
- 230000028993 immune response Effects 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 3
- 238000002955 isolation Methods 0.000 description 3
- 108010045069 keyhole-limpet hemocyanin Proteins 0.000 description 3
- 210000004698 lymphocyte Anatomy 0.000 description 3
- 239000011777 magnesium Substances 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 230000021121 meiosis Effects 0.000 description 3
- 239000002480 mineral oil Substances 0.000 description 3
- 235000010446 mineral oil Nutrition 0.000 description 3
- 210000000056 organ Anatomy 0.000 description 3
- 210000003463 organelle Anatomy 0.000 description 3
- 230000008520 organization Effects 0.000 description 3
- 210000001672 ovary Anatomy 0.000 description 3
- 108010091212 pepstatin Proteins 0.000 description 3
- FAXGPCHRFPCXOO-LXTPJMTPSA-N pepstatin A Chemical compound OC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)NC(=O)CC(C)C FAXGPCHRFPCXOO-LXTPJMTPSA-N 0.000 description 3
- 239000013612 plasmid Substances 0.000 description 3
- 230000002265 prevention Effects 0.000 description 3
- 102000004196 processed proteins & peptides Human genes 0.000 description 3
- 239000000007 protein synthesis inhibitor Substances 0.000 description 3
- 229950010131 puromycin Drugs 0.000 description 3
- 238000012216 screening Methods 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 3
- 239000007790 solid phase Substances 0.000 description 3
- 230000002269 spontaneous effect Effects 0.000 description 3
- 238000012289 standard assay Methods 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 238000010361 transduction Methods 0.000 description 3
- 230000026683 transduction Effects 0.000 description 3
- 238000013519 translation Methods 0.000 description 3
- 239000002753 trypsin inhibitor Substances 0.000 description 3
- 238000002604 ultrasonography Methods 0.000 description 3
- 210000004340 zona pellucida Anatomy 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- TZCPCKNHXULUIY-RGULYWFUSA-N 1,2-distearoyl-sn-glycero-3-phosphoserine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OC[C@H](N)C(O)=O)OC(=O)CCCCCCCCCCCCCCCCC TZCPCKNHXULUIY-RGULYWFUSA-N 0.000 description 2
- 231100000699 Bacterial toxin Toxicity 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- 102000000584 Calmodulin Human genes 0.000 description 2
- 108010041952 Calmodulin Proteins 0.000 description 2
- 241000282472 Canis lupus familiaris Species 0.000 description 2
- 241000282994 Cervidae Species 0.000 description 2
- 101000709520 Chlamydia trachomatis serovar L2 (strain 434/Bu / ATCC VR-902B) Atypical response regulator protein ChxR Proteins 0.000 description 2
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 2
- 102000004420 Creatine Kinase Human genes 0.000 description 2
- 108010042126 Creatine kinase Proteins 0.000 description 2
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 2
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 2
- 238000012286 ELISA Assay Methods 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 241000282326 Felis catus Species 0.000 description 2
- 241000287828 Gallus gallus Species 0.000 description 2
- 108700007698 Genetic Terminator Regions Proteins 0.000 description 2
- 208000034951 Genetic Translocation Diseases 0.000 description 2
- DHCLVCXQIBBOPH-UHFFFAOYSA-N Glycerol 2-phosphate Chemical compound OCC(CO)OP(O)(O)=O DHCLVCXQIBBOPH-UHFFFAOYSA-N 0.000 description 2
- ZWZWYGMENQVNFU-UHFFFAOYSA-N Glycerophosphorylserin Natural products OC(=O)C(N)COP(O)(=O)OCC(O)CO ZWZWYGMENQVNFU-UHFFFAOYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 102100030500 Heparin cofactor 2 Human genes 0.000 description 2
- 101001082432 Homo sapiens Heparin cofactor 2 Proteins 0.000 description 2
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 2
- 102000006496 Immunoglobulin Heavy Chains Human genes 0.000 description 2
- 108010019476 Immunoglobulin Heavy Chains Proteins 0.000 description 2
- 108010065825 Immunoglobulin Light Chains Proteins 0.000 description 2
- 102000013463 Immunoglobulin Light Chains Human genes 0.000 description 2
- 102000015696 Interleukins Human genes 0.000 description 2
- 108010063738 Interleukins Proteins 0.000 description 2
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 2
- 101150077556 LMNA gene Proteins 0.000 description 2
- 229920002274 Nalgene Polymers 0.000 description 2
- 229930193140 Neomycin Natural products 0.000 description 2
- 239000000020 Nitrocellulose Substances 0.000 description 2
- KYRVNWMVYQXFEU-UHFFFAOYSA-N Nocodazole Chemical compound C1=C2NC(NC(=O)OC)=NC2=CC=C1C(=O)C1=CC=CS1 KYRVNWMVYQXFEU-UHFFFAOYSA-N 0.000 description 2
- 108020004485 Nonsense Codon Proteins 0.000 description 2
- 108091005461 Nucleic proteins Proteins 0.000 description 2
- 239000004677 Nylon Substances 0.000 description 2
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 2
- 108010004729 Phycoerythrin Proteins 0.000 description 2
- 239000013614 RNA sample Substances 0.000 description 2
- 230000006819 RNA synthesis Effects 0.000 description 2
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
- 108010011834 Streptolysins Proteins 0.000 description 2
- 101710172711 Structural protein Proteins 0.000 description 2
- 102000006467 TATA-Box Binding Protein Human genes 0.000 description 2
- 108010044281 TATA-Box Binding Protein Proteins 0.000 description 2
- 230000005856 abnormality Effects 0.000 description 2
- 210000004504 adult stem cell Anatomy 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- 239000000688 bacterial toxin Substances 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- 230000005540 biological transmission Effects 0.000 description 2
- 210000001185 bone marrow Anatomy 0.000 description 2
- 244000309464 bull Species 0.000 description 2
- 210000004899 c-terminal region Anatomy 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 239000013592 cell lysate Substances 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- 239000013599 cloning vector Substances 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 238000012790 confirmation Methods 0.000 description 2
- 239000000562 conjugate Substances 0.000 description 2
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
- 150000001982 diacylglycerols Chemical class 0.000 description 2
- 108010067755 dinitrophenyl-bovine serum albumin Proteins 0.000 description 2
- 210000003981 ectoderm Anatomy 0.000 description 2
- 238000001378 electrochemiluminescence detection Methods 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 230000007717 exclusion Effects 0.000 description 2
- 239000012894 fetal calf serum Substances 0.000 description 2
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 2
- 238000012224 gene deletion Methods 0.000 description 2
- 238000012239 gene modification Methods 0.000 description 2
- 238000010363 gene targeting Methods 0.000 description 2
- 210000002149 gonad Anatomy 0.000 description 2
- 239000003102 growth factor Substances 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
- 239000005556 hormone Substances 0.000 description 2
- 210000003405 ileum Anatomy 0.000 description 2
- 230000001900 immune effect Effects 0.000 description 2
- 230000034435 immune system development Effects 0.000 description 2
- 230000010354 integration Effects 0.000 description 2
- 229940047122 interleukins Drugs 0.000 description 2
- 210000002570 interstitial cell Anatomy 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- PGHMRUGBZOYCAA-UHFFFAOYSA-N ionomycin Natural products O1C(CC(O)C(C)C(O)C(C)C=CCC(C)CC(C)C(O)=CC(=O)C(C)CC(C)CC(CCC(O)=O)C)CCC1(C)C1OC(C)(C(C)O)CC1 PGHMRUGBZOYCAA-UHFFFAOYSA-N 0.000 description 2
- PGHMRUGBZOYCAA-ADZNBVRBSA-N ionomycin Chemical compound O1[C@H](C[C@H](O)[C@H](C)[C@H](O)[C@H](C)/C=C/C[C@@H](C)C[C@@H](C)C(/O)=C/C(=O)[C@@H](C)C[C@@H](C)C[C@@H](CCC(O)=O)C)CC[C@@]1(C)[C@@H]1O[C@](C)([C@@H](C)O)CC1 PGHMRUGBZOYCAA-ADZNBVRBSA-N 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 238000001638 lipofection Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 230000013011 mating Effects 0.000 description 2
- 244000000010 microbial pathogen Species 0.000 description 2
- 230000011278 mitosis Effects 0.000 description 2
- 230000000877 morphologic effect Effects 0.000 description 2
- 239000004570 mortar (masonry) Substances 0.000 description 2
- 229960004927 neomycin Drugs 0.000 description 2
- 229920001220 nitrocellulos Polymers 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 229950006344 nocodazole Drugs 0.000 description 2
- 230000037434 nonsense mutation Effects 0.000 description 2
- 238000010899 nucleation Methods 0.000 description 2
- 229920001778 nylon Polymers 0.000 description 2
- 230000008182 oocyte development Effects 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 210000000496 pancreas Anatomy 0.000 description 2
- 239000011574 phosphorus Substances 0.000 description 2
- 229910052698 phosphorus Inorganic materials 0.000 description 2
- 229920003023 plastic Polymers 0.000 description 2
- 239000004033 plastic Substances 0.000 description 2
- 230000000069 prophylactic effect Effects 0.000 description 2
- 238000001243 protein synthesis Methods 0.000 description 2
- 230000006798 recombination Effects 0.000 description 2
- 238000005215 recombination Methods 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000011069 regeneration method Methods 0.000 description 2
- 230000001850 reproductive effect Effects 0.000 description 2
- 210000000582 semen Anatomy 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- ATHGHQPFGPMSJY-UHFFFAOYSA-N spermidine Chemical compound NCCCCNCCCN ATHGHQPFGPMSJY-UHFFFAOYSA-N 0.000 description 2
- PFNFFQXMRSDOHW-UHFFFAOYSA-N spermine Chemical compound NCCCNCCCCNCCCN PFNFFQXMRSDOHW-UHFFFAOYSA-N 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 108010075210 streptolysin O Proteins 0.000 description 2
- 229960005322 streptomycin Drugs 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 239000013589 supplement Substances 0.000 description 2
- 210000001550 testis Anatomy 0.000 description 2
- JGVWCANSWKRBCS-UHFFFAOYSA-N tetramethylrhodamine thiocyanate Chemical compound [Cl-].C=12C=CC(N(C)C)=CC2=[O+]C2=CC(N(C)C)=CC=C2C=1C1=CC=C(SC#N)C=C1C(O)=O JGVWCANSWKRBCS-UHFFFAOYSA-N 0.000 description 2
- 230000002103 transcriptional effect Effects 0.000 description 2
- 241000701161 unidentified adenovirus Species 0.000 description 2
- 210000002700 urine Anatomy 0.000 description 2
- 210000001835 viscera Anatomy 0.000 description 2
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 2
- ASWBNKHCZGQVJV-UHFFFAOYSA-N (3-hexadecanoyloxy-2-hydroxypropyl) 2-(trimethylazaniumyl)ethyl phosphate Chemical compound CCCCCCCCCCCCCCCC(=O)OCC(O)COP([O-])(=O)OCC[N+](C)(C)C ASWBNKHCZGQVJV-UHFFFAOYSA-N 0.000 description 1
- BHNQPLPANNDEGL-UHFFFAOYSA-N 2-(4-octylphenoxy)ethanol Chemical compound CCCCCCCCC1=CC=C(OCCO)C=C1 BHNQPLPANNDEGL-UHFFFAOYSA-N 0.000 description 1
- IDOQDZANRZQBTP-UHFFFAOYSA-N 2-[2-(2,4,4-trimethylpentan-2-yl)phenoxy]ethanol Chemical compound CC(C)(C)CC(C)(C)C1=CC=CC=C1OCCO IDOQDZANRZQBTP-UHFFFAOYSA-N 0.000 description 1
- UMCMPZBLKLEWAF-BCTGSCMUSA-N 3-[(3-cholamidopropyl)dimethylammonio]propane-1-sulfonate Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCCC[N+](C)(C)CCCS([O-])(=O)=O)C)[C@@]2(C)[C@@H](O)C1 UMCMPZBLKLEWAF-BCTGSCMUSA-N 0.000 description 1
- FWBHETKCLVMNFS-UHFFFAOYSA-N 4',6-Diamino-2-phenylindol Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC2=CC=C(C(N)=N)C=C2N1 FWBHETKCLVMNFS-UHFFFAOYSA-N 0.000 description 1
- CYDQOEWLBCCFJZ-UHFFFAOYSA-N 4-(4-fluorophenyl)oxane-4-carboxylic acid Chemical compound C=1C=C(F)C=CC=1C1(C(=O)O)CCOCC1 CYDQOEWLBCCFJZ-UHFFFAOYSA-N 0.000 description 1
- 102100031912 A-kinase anchor protein 1, mitochondrial Human genes 0.000 description 1
- 241000282979 Alces alces Species 0.000 description 1
- 235000002198 Annona diversifolia Nutrition 0.000 description 1
- 208000019901 Anxiety disease Diseases 0.000 description 1
- 102100021569 Apoptosis regulator Bcl-2 Human genes 0.000 description 1
- 101100177160 Arabidopsis thaliana HAC2 gene Proteins 0.000 description 1
- 101100302211 Arabidopsis thaliana RNR2A gene Proteins 0.000 description 1
- 102000015081 Blood Coagulation Factors Human genes 0.000 description 1
- 108010039209 Blood Coagulation Factors Proteins 0.000 description 1
- 241000283725 Bos Species 0.000 description 1
- 101000693922 Bos taurus Albumin Proteins 0.000 description 1
- 241000282817 Bovidae Species 0.000 description 1
- 229960005532 CC-1065 Drugs 0.000 description 1
- 241000282832 Camelidae Species 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- 102000000844 Cell Surface Receptors Human genes 0.000 description 1
- 108010001857 Cell Surface Receptors Proteins 0.000 description 1
- 206010068051 Chimerism Diseases 0.000 description 1
- 241001550206 Colla Species 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 108010051219 Cre recombinase Proteins 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- 241000699802 Cricetulus griseus Species 0.000 description 1
- 101710112752 Cytotoxin Proteins 0.000 description 1
- 238000007400 DNA extraction Methods 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- SHIBSTMRCDJXLN-UHFFFAOYSA-N Digoxigenin Natural products C1CC(C2C(C3(C)CCC(O)CC3CC2)CC2O)(O)C2(C)C1C1=CC(=O)OC1 SHIBSTMRCDJXLN-UHFFFAOYSA-N 0.000 description 1
- 102000016607 Diphtheria Toxin Human genes 0.000 description 1
- 108010053187 Diphtheria Toxin Proteins 0.000 description 1
- 241000257465 Echinoidea Species 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 241000283074 Equus asinus Species 0.000 description 1
- 241001331845 Equus asinus x caballus Species 0.000 description 1
- 102000009109 Fc receptors Human genes 0.000 description 1
- 108010087819 Fc receptors Proteins 0.000 description 1
- 206010064571 Gene mutation Diseases 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 108010043121 Green Fluorescent Proteins Proteins 0.000 description 1
- 102000004144 Green Fluorescent Proteins Human genes 0.000 description 1
- 102000003964 Histone deacetylase Human genes 0.000 description 1
- 108090000353 Histone deacetylase Proteins 0.000 description 1
- 101000774717 Homo sapiens A-kinase anchor protein 1, mitochondrial Proteins 0.000 description 1
- 101000971171 Homo sapiens Apoptosis regulator Bcl-2 Proteins 0.000 description 1
- 101000741910 Homo sapiens Protein phosphatase 1 regulatory subunit 7 Proteins 0.000 description 1
- 101000741917 Homo sapiens Serine/threonine-protein phosphatase 1 regulatory subunit 10 Proteins 0.000 description 1
- 101000639792 Homo sapiens U2 small nuclear ribonucleoprotein A' Proteins 0.000 description 1
- 241000701044 Human gammaherpesvirus 4 Species 0.000 description 1
- GRRNUXAQVGOGFE-UHFFFAOYSA-N Hygromycin-B Natural products OC1C(NC)CC(N)C(O)C1OC1C2OC3(C(C(O)C(O)C(C(N)CO)O3)O)OC2C(O)C(CO)O1 GRRNUXAQVGOGFE-UHFFFAOYSA-N 0.000 description 1
- 206010061598 Immunodeficiency Diseases 0.000 description 1
- 208000029462 Immunodeficiency disease Diseases 0.000 description 1
- 229930182816 L-glutamine Natural products 0.000 description 1
- 241000282838 Lama Species 0.000 description 1
- 239000000232 Lipid Bilayer Substances 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 101100496858 Mus musculus Colec12 gene Proteins 0.000 description 1
- 101100070236 Mus musculus Hcn1 gene Proteins 0.000 description 1
- 241001045988 Neogene Species 0.000 description 1
- 101100384865 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) cot-1 gene Proteins 0.000 description 1
- 102000007999 Nuclear Proteins Human genes 0.000 description 1
- 108010089610 Nuclear Proteins Proteins 0.000 description 1
- 102000003789 Nuclear pore complex proteins Human genes 0.000 description 1
- 108090000163 Nuclear pore complex proteins Proteins 0.000 description 1
- 101710163270 Nuclease Proteins 0.000 description 1
- 241000283903 Ovis aries Species 0.000 description 1
- 241001502414 Ovis canadensis Species 0.000 description 1
- 238000012408 PCR amplification Methods 0.000 description 1
- 241000283089 Perissodactyla Species 0.000 description 1
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
- 239000004952 Polyamide Substances 0.000 description 1
- 229920002535 Polyethylene Glycol 1500 Polymers 0.000 description 1
- 241000283080 Proboscidea <mammal> Species 0.000 description 1
- 102000003946 Prolactin Human genes 0.000 description 1
- 108010057464 Prolactin Proteins 0.000 description 1
- 102100038755 Protein phosphatase 1 regulatory subunit 7 Human genes 0.000 description 1
- 102000004097 Protein phosphatase inhibitor 1 Human genes 0.000 description 1
- 108090000506 Protein phosphatase inhibitor 1 Proteins 0.000 description 1
- LCTONWCANYUPML-UHFFFAOYSA-M Pyruvate Chemical compound CC(=O)C([O-])=O LCTONWCANYUPML-UHFFFAOYSA-M 0.000 description 1
- 102000009572 RNA Polymerase II Human genes 0.000 description 1
- 108010009460 RNA Polymerase II Proteins 0.000 description 1
- 239000013616 RNA primer Substances 0.000 description 1
- 101150002896 RNR2 gene Proteins 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 239000012722 SDS sample buffer Substances 0.000 description 1
- 102100038743 Serine/threonine-protein phosphatase 1 regulatory subunit 10 Human genes 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 241001493546 Suina Species 0.000 description 1
- 239000006180 TBST buffer Substances 0.000 description 1
- 229940123237 Taxane Drugs 0.000 description 1
- 108010017842 Telomerase Proteins 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 229920004929 Triton X-114 Polymers 0.000 description 1
- GLNADSQYFUSGOU-GPTZEZBUSA-J Trypan blue Chemical compound [Na+].[Na+].[Na+].[Na+].C1=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(/N=N/C3=CC=C(C=C3C)C=3C=C(C(=CC=3)\N=N\C=3C(=CC4=CC(=CC(N)=C4C=3O)S([O-])(=O)=O)S([O-])(=O)=O)C)=C(O)C2=C1N GLNADSQYFUSGOU-GPTZEZBUSA-J 0.000 description 1
- 102100034465 U2 small nuclear ribonucleoprotein A' Human genes 0.000 description 1
- 241001416177 Vicugna pacos Species 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 230000009824 affinity maturation Effects 0.000 description 1
- 238000001261 affinity purification Methods 0.000 description 1
- 238000005054 agglomeration Methods 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- APKFDSVGJQXUKY-INPOYWNPSA-N amphotericin B Chemical compound O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/C=C/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-INPOYWNPSA-N 0.000 description 1
- 229940045799 anthracyclines and related substance Drugs 0.000 description 1
- 238000009175 antibody therapy Methods 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 238000003491 array Methods 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 239000012472 biological sample Substances 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 238000005422 blasting Methods 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 239000003114 blood coagulation factor Substances 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 239000007975 buffered saline Substances 0.000 description 1
- OEERIBPGRSLGEK-UHFFFAOYSA-N carbon dioxide;methanol Chemical compound OC.O=C=O OEERIBPGRSLGEK-UHFFFAOYSA-N 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000011712 cell development Effects 0.000 description 1
- 108091092356 cellular DNA Proteins 0.000 description 1
- 210000002230 centromere Anatomy 0.000 description 1
- 108091006090 chromatin-associated proteins Proteins 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 230000008045 co-localization Effects 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 230000024203 complement activation Effects 0.000 description 1
- 239000000356 contaminant Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000013601 cosmid vector Substances 0.000 description 1
- 230000037029 cross reaction Effects 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 229940104302 cytosine Drugs 0.000 description 1
- 230000003436 cytoskeletal effect Effects 0.000 description 1
- 210000000172 cytosol Anatomy 0.000 description 1
- 231100000599 cytotoxic agent Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 239000002619 cytotoxin Substances 0.000 description 1
- 235000013365 dairy product Nutrition 0.000 description 1
- 238000000326 densiometry Methods 0.000 description 1
- 229940009976 deoxycholate Drugs 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- UQLDLKMNUJERMK-UHFFFAOYSA-L di(octadecanoyloxy)lead Chemical compound [Pb+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O UQLDLKMNUJERMK-UHFFFAOYSA-L 0.000 description 1
- 238000001085 differential centrifugation Methods 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- QONQRTHLHBTMGP-UHFFFAOYSA-N digitoxigenin Natural products CC12CCC(C3(CCC(O)CC3CC3)C)C3C11OC1CC2C1=CC(=O)OC1 QONQRTHLHBTMGP-UHFFFAOYSA-N 0.000 description 1
- SHIBSTMRCDJXLN-KCZCNTNESA-N digoxigenin Chemical compound C1([C@@H]2[C@@]3([C@@](CC2)(O)[C@H]2[C@@H]([C@@]4(C)CC[C@H](O)C[C@H]4CC2)C[C@H]3O)C)=CC(=O)OC1 SHIBSTMRCDJXLN-KCZCNTNESA-N 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 235000011180 diphosphates Nutrition 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 241001493065 dsRNA viruses Species 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 210000002969 egg yolk Anatomy 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 239000008393 encapsulating agent Substances 0.000 description 1
- 210000003238 esophagus Anatomy 0.000 description 1
- 239000003797 essential amino acid Substances 0.000 description 1
- 235000020776 essential amino acid Nutrition 0.000 description 1
- DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000013401 experimental design Methods 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 210000003414 extremity Anatomy 0.000 description 1
- 238000000799 fluorescence microscopy Methods 0.000 description 1
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 238000002509 fluorescent in situ hybridization Methods 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 231100000221 frame shift mutation induction Toxicity 0.000 description 1
- 230000037433 frameshift Effects 0.000 description 1
- 238000007306 functionalization reaction Methods 0.000 description 1
- 230000000799 fusogenic effect Effects 0.000 description 1
- 229930182830 galactose Natural products 0.000 description 1
- 125000002519 galactosyl group Chemical group C1([C@H](O)[C@@H](O)[C@@H](O)[C@H](O1)CO)* 0.000 description 1
- 210000000232 gallbladder Anatomy 0.000 description 1
- 238000001502 gel electrophoresis Methods 0.000 description 1
- 230000005017 genetic modification Effects 0.000 description 1
- 230000007614 genetic variation Effects 0.000 description 1
- 235000013617 genetically modified food Nutrition 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 239000005090 green fluorescent protein Substances 0.000 description 1
- 230000037308 hair color Effects 0.000 description 1
- 210000003128 head Anatomy 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 210000002216 heart Anatomy 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- GRRNUXAQVGOGFE-NZSRVPFOSA-N hygromycin B Chemical compound O[C@@H]1[C@@H](NC)C[C@@H](N)[C@H](O)[C@H]1O[C@H]1[C@H]2O[C@@]3([C@@H]([C@@H](O)[C@@H](O)[C@@H](C(N)CO)O3)O)O[C@H]2[C@@H](O)[C@@H](CO)O1 GRRNUXAQVGOGFE-NZSRVPFOSA-N 0.000 description 1
- 229940097277 hygromycin b Drugs 0.000 description 1
- 230000036737 immune function Effects 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000007813 immunodeficiency Effects 0.000 description 1
- 238000003318 immunodepletion Methods 0.000 description 1
- 238000003125 immunofluorescent labeling Methods 0.000 description 1
- 238000001114 immunoprecipitation Methods 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 238000007901 in situ hybridization Methods 0.000 description 1
- 238000011503 in vivo imaging Methods 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 229940008228 intravenous immunoglobulins Drugs 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 238000000021 kinase assay Methods 0.000 description 1
- 125000005647 linker group Chemical group 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 210000000415 mammalian chromosome Anatomy 0.000 description 1
- 210000005075 mammary gland Anatomy 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 210000005060 membrane bound organelle Anatomy 0.000 description 1
- 238000000386 microscopy Methods 0.000 description 1
- 238000001823 molecular biology technique Methods 0.000 description 1
- 239000003147 molecular marker Substances 0.000 description 1
- 230000004660 morphological change Effects 0.000 description 1
- 230000001459 mortal effect Effects 0.000 description 1
- 238000002703 mutagenesis Methods 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- IUJLOAKJZQBENM-UHFFFAOYSA-N n-(1,3-benzothiazol-2-ylsulfanyl)-2-methylpropan-2-amine Chemical compound C1=CC=C2SC(SNC(C)(C)C)=NC2=C1 IUJLOAKJZQBENM-UHFFFAOYSA-N 0.000 description 1
- 210000003928 nasal cavity Anatomy 0.000 description 1
- 101150091879 neo gene Proteins 0.000 description 1
- 238000007857 nested PCR Methods 0.000 description 1
- 230000006911 nucleation Effects 0.000 description 1
- HEGSGKPQLMEBJL-RKQHYHRCSA-N octyl beta-D-glucopyranoside Chemical compound CCCCCCCCO[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O HEGSGKPQLMEBJL-RKQHYHRCSA-N 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 210000004789 organ system Anatomy 0.000 description 1
- 230000002611 ovarian Effects 0.000 description 1
- 238000007500 overflow downdraw method Methods 0.000 description 1
- 210000003101 oviduct Anatomy 0.000 description 1
- 210000004681 ovum Anatomy 0.000 description 1
- 238000002559 palpation Methods 0.000 description 1
- 238000004091 panning Methods 0.000 description 1
- 244000045947 parasite Species 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 239000012466 permeate Substances 0.000 description 1
- 230000002688 persistence Effects 0.000 description 1
- 210000001986 peyer's patch Anatomy 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 1
- 229920002647 polyamide Polymers 0.000 description 1
- 229920000768 polyamine Polymers 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 229940097325 prolactin Drugs 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- XJMOSONTPMZWPB-UHFFFAOYSA-M propidium iodide Chemical compound [I-].[I-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CCC[N+](C)(CC)CC)=C1C1=CC=CC=C1 XJMOSONTPMZWPB-UHFFFAOYSA-M 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 229940070353 protamines Drugs 0.000 description 1
- 229940076788 pyruvate Drugs 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 239000001397 quillaja saponaria molina bark Substances 0.000 description 1
- UOWVMDUEMSNCAV-WYENRQIDSA-N rachelmycin Chemical compound C1([C@]23C[C@@H]2CN1C(=O)C=1NC=2C(OC)=C(O)C4=C(C=2C=1)CCN4C(=O)C1=CC=2C=4CCN(C=4C(O)=C(C=2N1)OC)C(N)=O)=CC(=O)C1=C3C(C)=CN1 UOWVMDUEMSNCAV-WYENRQIDSA-N 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 230000001177 retroviral effect Effects 0.000 description 1
- 238000010839 reverse transcription Methods 0.000 description 1
- 238000010079 rubber tapping Methods 0.000 description 1
- 229930182490 saponin Natural products 0.000 description 1
- 150000007949 saponins Chemical class 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000002864 sequence alignment Methods 0.000 description 1
- 230000037432 silent mutation Effects 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 239000001540 sodium lactate Substances 0.000 description 1
- 229940005581 sodium lactate Drugs 0.000 description 1
- 235000011088 sodium lactate Nutrition 0.000 description 1
- 229940063673 spermidine Drugs 0.000 description 1
- 229940063675 spermine Drugs 0.000 description 1
- 210000000278 spinal cord Anatomy 0.000 description 1
- 230000003393 splenic effect Effects 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 108010071614 streptocin Proteins 0.000 description 1
- FRGKKTITADJNOE-UHFFFAOYSA-N sulfanyloxyethane Chemical compound CCOS FRGKKTITADJNOE-UHFFFAOYSA-N 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- DKPFODGZWDEEBT-QFIAKTPHSA-N taxane Chemical class C([C@]1(C)CCC[C@@H](C)[C@H]1C1)C[C@H]2[C@H](C)CC[C@@H]1C2(C)C DKPFODGZWDEEBT-QFIAKTPHSA-N 0.000 description 1
- 210000001541 thymus gland Anatomy 0.000 description 1
- 210000001685 thyroid gland Anatomy 0.000 description 1
- 210000003437 trachea Anatomy 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
- WBPYTXDJUQJLPQ-VMXQISHHSA-N tylosin Chemical compound O([C@@H]1[C@@H](C)O[C@H]([C@@H]([C@H]1N(C)C)O)O[C@@H]1[C@@H](C)[C@H](O)CC(=O)O[C@@H]([C@H](/C=C(\C)/C=C/C(=O)[C@H](C)C[C@@H]1CC=O)CO[C@H]1[C@@H]([C@H](OC)[C@H](O)[C@@H](C)O1)OC)CC)[C@H]1C[C@@](C)(O)[C@@H](O)[C@H](C)O1 WBPYTXDJUQJLPQ-VMXQISHHSA-N 0.000 description 1
- 210000003954 umbilical cord Anatomy 0.000 description 1
- 210000000626 ureter Anatomy 0.000 description 1
- 210000003708 urethra Anatomy 0.000 description 1
- 210000003932 urinary bladder Anatomy 0.000 description 1
- 238000010200 validation analysis Methods 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 238000003260 vortexing Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 210000005253 yeast cell Anatomy 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K67/00—Rearing or breeding animals, not otherwise provided for; New or modified breeds of animals
- A01K67/027—New or modified breeds of vertebrates
- A01K67/0275—Genetically modified vertebrates, e.g. transgenic
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K67/00—Rearing or breeding animals, not otherwise provided for; New or modified breeds of animals
- A01K67/027—New or modified breeds of vertebrates
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
- C12N15/8509—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells for producing genetically modified animals, e.g. transgenic
-
- 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
- C12N15/87—Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
- C12N15/873—Techniques for producing new embryos, e.g. nuclear transfer, manipulation of totipotent cells or production of chimeric embryos
- C12N15/877—Techniques for producing new mammalian cloned embryos
- C12N15/8773—Ovine embryos
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2207/00—Modified animals
- A01K2207/15—Humanized animals
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2217/00—Genetically modified animals
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2227/00—Animals characterised by species
- A01K2227/10—Mammal
- A01K2227/101—Bovine
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2267/00—Animals characterised by purpose
- A01K2267/01—Animal expressing industrially exogenous proteins
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Engineering & Computer Science (AREA)
- Zoology (AREA)
- Biotechnology (AREA)
- Biomedical Technology (AREA)
- Wood Science & Technology (AREA)
- Organic Chemistry (AREA)
- General Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Environmental Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Biophysics (AREA)
- Animal Behavior & Ethology (AREA)
- Plant Pathology (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Physics & Mathematics (AREA)
- Veterinary Medicine (AREA)
- Microbiology (AREA)
- Animal Husbandry (AREA)
- Biodiversity & Conservation Biology (AREA)
- Developmental Biology & Embryology (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Peptides Or Proteins (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US38153102P | 2002-05-17 | 2002-05-17 | |
| US60/381,531 | 2002-05-17 | ||
| US42505602P | 2002-11-08 | 2002-11-08 | |
| US60/425,056 | 2002-11-08 | ||
| PCT/US2003/015937 WO2003097812A2 (en) | 2002-05-17 | 2003-05-19 | Transgenic ungulates capable of human antibody production |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20050000558A true KR20050000558A (ko) | 2005-01-05 |
Family
ID=29553536
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR10-2004-7018599A Ceased KR20050000558A (ko) | 2002-05-17 | 2003-05-19 | 인간 항체를 제조할 수 있는 트랜스제닉 유제동물 |
Country Status (10)
| Country | Link |
|---|---|
| EP (1) | EP1513397B1 (enExample) |
| JP (1) | JP2005525817A (enExample) |
| KR (1) | KR20050000558A (enExample) |
| CN (1) | CN1668187A (enExample) |
| AT (1) | ATE464389T1 (enExample) |
| CA (1) | CA2484655A1 (enExample) |
| DE (1) | DE60332111D1 (enExample) |
| IL (1) | IL165088A0 (enExample) |
| NZ (1) | NZ536341A (enExample) |
| WO (1) | WO2003097812A2 (enExample) |
Families Citing this family (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0110029D0 (en) | 2001-04-24 | 2001-06-13 | Grosveld Frank | Transgenic animal |
| WO2005104835A2 (en) * | 2004-04-22 | 2005-11-10 | Kirin Beer Kabushiki Kaisha | Transgenic animals and uses thereof |
| US8785187B2 (en) * | 2004-06-09 | 2014-07-22 | The University Court Of The University Of Edinburgh | Neural stem cells |
| CA2958259C (en) * | 2004-10-22 | 2020-06-30 | Revivicor, Inc. | Ungulates with genetically modified immune systems |
| TW200817512A (en) | 2006-07-07 | 2008-04-16 | Kirin Pharma Kk | Human artificial chromosome (hac) vector, and human cell pharmaceutical comprising human artificial chromosome (hac) vector |
| DK2348827T3 (en) | 2008-10-27 | 2015-07-20 | Revivicor Inc | IMMUNICIPLY COMPROMATED PETS |
| EP3187581A1 (en) | 2008-12-23 | 2017-07-05 | BOCO Silicon Valley, Inc. | Target populations of oligodendrocyte precursor cells and methods of making and using same |
| CN102711804B (zh) | 2009-11-13 | 2015-09-16 | 赛诺菲-安万特德国有限公司 | 包含glp-1激动剂和甲硫氨酸的药物组合物 |
| CN102803488A (zh) | 2009-11-17 | 2012-11-28 | 协和发酵麒麟株式会社 | 人类人工染色体载体 |
| CN104755493B (zh) * | 2012-08-03 | 2020-12-25 | Sab有限责任公司 | 用于在转基因动物中生产人类抗体的复杂的染色体工程 |
| EP2956484B1 (en) * | 2013-02-13 | 2018-11-14 | Laboratoire Français du Fractionnement et des Biotechnologies | Cetuximab with modified glycosylation and uses thereof |
| EA038968B1 (ru) * | 2013-04-18 | 2021-11-16 | Институт Насьональ Де Ла Сант Эт Де Ла Решерш Медикаль | Композиция с пониженной иммуногенностью |
| CN107001449A (zh) * | 2014-10-15 | 2017-08-01 | 芝诺锡拉公司 | 具有降低的免疫原性的组合物 |
| EP4103603A4 (en) * | 2020-02-12 | 2024-03-27 | Sab, Llc | ANTI-THYMOCYTE GLOBULIN |
| EP4665391A1 (en) * | 2023-02-17 | 2025-12-24 | Sab, Llc | Ungulate-derived polyclonal immunoglobulin specific for influenza virus and uses thereof |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5652373A (en) * | 1990-01-15 | 1997-07-29 | Yeda Research And Development Co. Ltd. | Engraftment and development of xenogeneic cells in normal mammals having reconstituted hematopoetic deficient immune systems |
| US6300129B1 (en) | 1990-08-29 | 2001-10-09 | Genpharm International | Transgenic non-human animals for producing heterologous antibodies |
| CA2089661C (en) * | 1990-08-29 | 2007-04-03 | Nils Lonberg | Transgenic non-human animals capable of producing heterologous antibodies |
| US5545806A (en) * | 1990-08-29 | 1996-08-13 | Genpharm International, Inc. | Ransgenic non-human animals for producing heterologous antibodies |
| US5770429A (en) | 1990-08-29 | 1998-06-23 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| US5827690A (en) | 1993-12-20 | 1998-10-27 | Genzyme Transgenics Corporatiion | Transgenic production of antibodies in milk |
| US5789655A (en) * | 1994-05-13 | 1998-08-04 | The Regents Of The University Of California | Transgenic animals expressing artificial epitope-tagged proteins |
| ATE390933T1 (de) | 1995-04-27 | 2008-04-15 | Amgen Fremont Inc | Aus immunisierten xenomäusen stammende menschliche antikörper gegen il-8 |
| AU718138B2 (en) * | 1995-08-29 | 2000-04-06 | Kyowa Hakko Kirin Co., Ltd. | Chimeric animal and method for constructing the same |
| EP2314625B1 (en) | 1996-12-03 | 2014-05-07 | Amgen Fremont Inc. | Transgenic mammals having human Ig loci including plural VH and Vkappa regions and antibodies produced therefrom |
| AU1777301A (en) * | 1999-11-19 | 2001-05-30 | Hematech, Llc | Production of ungulates, preferably bovines that produce human immunoglobulins |
| WO2002070648A2 (en) * | 2000-11-17 | 2002-09-12 | Hematech, Llc | Expression of xenogenous (human) immunoglobulins in cloned, transgenic ungulates |
| US20020108132A1 (en) * | 2001-02-02 | 2002-08-08 | Avigenics Inc. | Production of a monoclonal antibody by a transgenic chicken |
-
2003
- 2003-05-19 NZ NZ536341A patent/NZ536341A/en unknown
- 2003-05-19 CA CA002484655A patent/CA2484655A1/en not_active Abandoned
- 2003-05-19 KR KR10-2004-7018599A patent/KR20050000558A/ko not_active Ceased
- 2003-05-19 AT AT03738939T patent/ATE464389T1/de not_active IP Right Cessation
- 2003-05-19 EP EP03738939A patent/EP1513397B1/en not_active Expired - Lifetime
- 2003-05-19 JP JP2004506471A patent/JP2005525817A/ja active Pending
- 2003-05-19 IL IL16508803A patent/IL165088A0/xx unknown
- 2003-05-19 WO PCT/US2003/015937 patent/WO2003097812A2/en not_active Ceased
- 2003-05-19 DE DE60332111T patent/DE60332111D1/de not_active Expired - Lifetime
- 2003-05-19 CN CNA038167425A patent/CN1668187A/zh active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| EP1513397A2 (en) | 2005-03-16 |
| NZ536341A (en) | 2008-05-30 |
| WO2003097812A2 (en) | 2003-11-27 |
| IL165088A0 (en) | 2005-12-18 |
| CN1668187A (zh) | 2005-09-14 |
| EP1513397A4 (en) | 2007-10-24 |
| AU2003245300A1 (en) | 2003-12-02 |
| ATE464389T1 (de) | 2010-04-15 |
| EP1513397B1 (en) | 2010-04-14 |
| WO2003097812A3 (en) | 2004-02-12 |
| DE60332111D1 (de) | 2010-05-27 |
| CA2484655A1 (en) | 2003-11-27 |
| JP2005525817A (ja) | 2005-09-02 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US7803981B2 (en) | Transgenic ungulates capable of human antibody production | |
| US7807863B2 (en) | Transgenic bovine having reduced prion protein activity and uses thereof | |
| KR100882029B1 (ko) | 클로닝된 트랜스제닉 유제류에서 이종 (사람)면역글로블린의 발현 | |
| US7928285B2 (en) | Method of producing xenogenous antibodies using a bovine | |
| US20110067122A1 (en) | Expression of Xenogenous (Human) Immunoglobulins in cloned, transgenic ungulates | |
| JP2005504507A5 (enExample) | ||
| KR20050000558A (ko) | 인간 항체를 제조할 수 있는 트랜스제닉 유제동물 | |
| CN100526460C (zh) | 朊病毒蛋白活性降低的转基因有蹄类动物及其用途 | |
| AU2003245300B2 (en) | Transgenic ungulates capable of human antibody production | |
| US20090276866A1 (en) | Production of ungulates, preferably bovines that produce human immunoglobulins |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PA0105 | International application |
Patent event date: 20041117 Patent event code: PA01051R01D Comment text: International Patent Application |
|
| PG1501 | Laying open of application | ||
| N231 | Notification of change of applicant | ||
| PN2301 | Change of applicant |
Patent event date: 20070406 Comment text: Notification of Change of Applicant Patent event code: PN23011R01D |
|
| N231 | Notification of change of applicant | ||
| PN2301 | Change of applicant |
Patent event date: 20071009 Comment text: Notification of Change of Applicant Patent event code: PN23011R01D |
|
| A201 | Request for examination | ||
| PA0201 | Request for examination |
Patent event code: PA02012R01D Patent event date: 20080519 Comment text: Request for Examination of Application |
|
| E902 | Notification of reason for refusal | ||
| PE0902 | Notice of grounds for rejection |
Comment text: Notification of reason for refusal Patent event date: 20100730 Patent event code: PE09021S01D |
|
| E601 | Decision to refuse application | ||
| PE0601 | Decision on rejection of patent |
Patent event date: 20101018 Comment text: Decision to Refuse Application Patent event code: PE06012S01D Patent event date: 20100730 Comment text: Notification of reason for refusal Patent event code: PE06011S01I |