ES2877275T3 - Animales con dipeptidil peptidasa IV (DPP4) humanizada - Google Patents
Animales con dipeptidil peptidasa IV (DPP4) humanizada Download PDFInfo
- Publication number
- ES2877275T3 ES2877275T3 ES18173004T ES18173004T ES2877275T3 ES 2877275 T3 ES2877275 T3 ES 2877275T3 ES 18173004 T ES18173004 T ES 18173004T ES 18173004 T ES18173004 T ES 18173004T ES 2877275 T3 ES2877275 T3 ES 2877275T3
- Authority
- ES
- Spain
- Prior art keywords
- dpp4
- rodent
- human
- gene
- dpp4 gene
- 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.)
- Active
Links
- 241001465754 Metazoa Species 0.000 title description 15
- 102000016622 Dipeptidyl Peptidase 4 Human genes 0.000 title description 8
- 101000930822 Giardia intestinalis Dipeptidyl-peptidase 4 Proteins 0.000 title description 6
- 241000283984 Rodentia Species 0.000 claims abstract description 271
- 101150093210 DPP4 gene Proteins 0.000 claims abstract description 204
- 101100332180 Homo sapiens DPP4 gene Proteins 0.000 claims abstract description 179
- 241000127282 Middle East respiratory syndrome-related coronavirus Species 0.000 claims abstract description 157
- 101000908391 Homo sapiens Dipeptidyl peptidase 4 Proteins 0.000 claims abstract description 103
- 102000045598 human DPP4 Human genes 0.000 claims abstract description 95
- 239000012634 fragment Substances 0.000 claims abstract description 94
- 230000001105 regulatory effect Effects 0.000 claims abstract description 33
- 230000014509 gene expression Effects 0.000 claims abstract description 18
- 206010035664 Pneumonia Diseases 0.000 claims abstract description 9
- 102100025012 Dipeptidyl peptidase 4 Human genes 0.000 claims description 126
- 210000004027 cell Anatomy 0.000 claims description 79
- 208000015181 infectious disease Diseases 0.000 claims description 78
- 101100332181 Mus musculus Dpp4 gene Proteins 0.000 claims description 51
- 108090000623 proteins and genes Proteins 0.000 claims description 48
- 239000005557 antagonist Substances 0.000 claims description 45
- 238000000034 method Methods 0.000 claims description 28
- 230000001225 therapeutic effect Effects 0.000 claims description 27
- 102000004169 proteins and genes Human genes 0.000 claims description 26
- 210000001161 mammalian embryo Anatomy 0.000 claims description 20
- 208000024891 symptom Diseases 0.000 claims description 8
- 229940090124 dipeptidyl peptidase 4 (dpp-4) inhibitors for blood glucose lowering Drugs 0.000 claims description 7
- 229940096437 Protein S Drugs 0.000 claims description 6
- 101710198474 Spike protein Proteins 0.000 claims description 6
- 210000001671 embryonic stem cell Anatomy 0.000 claims description 5
- 230000000069 prophylactic effect Effects 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 124
- 241000699670 Mus sp. Species 0.000 description 110
- 210000004072 lung Anatomy 0.000 description 72
- 241000700159 Rattus Species 0.000 description 67
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 34
- 238000003753 real-time PCR Methods 0.000 description 32
- 108700024394 Exon Proteins 0.000 description 28
- 238000011144 upstream manufacturing Methods 0.000 description 25
- 210000001744 T-lymphocyte Anatomy 0.000 description 24
- 238000003556 assay Methods 0.000 description 24
- 239000000523 sample Substances 0.000 description 24
- 210000001519 tissue Anatomy 0.000 description 21
- 210000004436 artificial bacterial chromosome Anatomy 0.000 description 20
- 238000001727 in vivo Methods 0.000 description 20
- 206010061218 Inflammation Diseases 0.000 description 19
- 230000004054 inflammatory process Effects 0.000 description 19
- 230000003612 virological effect Effects 0.000 description 19
- 108700028369 Alleles Proteins 0.000 description 18
- 150000007523 nucleic acids Chemical group 0.000 description 18
- 208000025370 Middle East respiratory syndrome Diseases 0.000 description 16
- 210000002865 immune cell Anatomy 0.000 description 16
- 238000011830 transgenic mouse model Methods 0.000 description 16
- 241000699660 Mus musculus Species 0.000 description 15
- 150000001413 amino acids Chemical class 0.000 description 15
- 108020005029 5' Flanking Region Proteins 0.000 description 14
- 210000004556 brain Anatomy 0.000 description 14
- 210000002216 heart Anatomy 0.000 description 14
- 210000003734 kidney Anatomy 0.000 description 14
- 210000004185 liver Anatomy 0.000 description 14
- 210000000496 pancreas Anatomy 0.000 description 14
- 210000002826 placenta Anatomy 0.000 description 14
- 102000004196 processed proteins & peptides Human genes 0.000 description 14
- 108090000765 processed proteins & peptides Proteins 0.000 description 14
- 210000002027 skeletal muscle Anatomy 0.000 description 14
- 108020004414 DNA Proteins 0.000 description 13
- 241000700605 Viruses Species 0.000 description 13
- 108091028043 Nucleic acid sequence Proteins 0.000 description 12
- 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 12
- 230000007170 pathology Effects 0.000 description 12
- 239000002953 phosphate buffered saline Substances 0.000 description 12
- 102000005962 receptors Human genes 0.000 description 12
- 108020003175 receptors Proteins 0.000 description 12
- 239000002773 nucleotide Substances 0.000 description 11
- 125000003729 nucleotide group Chemical group 0.000 description 11
- 230000008685 targeting Effects 0.000 description 11
- 238000011282 treatment Methods 0.000 description 11
- 108091036066 Three prime untranslated region Proteins 0.000 description 10
- 108020004705 Codon Proteins 0.000 description 9
- 238000005516 engineering process Methods 0.000 description 9
- 230000003285 pharmacodynamic effect Effects 0.000 description 9
- 230000002829 reductive effect Effects 0.000 description 9
- 108700039691 Genetic Promoter Regions Proteins 0.000 description 8
- 125000003275 alpha amino acid group Chemical group 0.000 description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 8
- 239000003550 marker Substances 0.000 description 8
- 239000000203 mixture Substances 0.000 description 8
- 108020000999 Viral RNA Proteins 0.000 description 7
- 208000036142 Viral infection Diseases 0.000 description 7
- 210000004369 blood Anatomy 0.000 description 7
- 239000008280 blood Substances 0.000 description 7
- 210000000349 chromosome Anatomy 0.000 description 7
- 150000003384 small molecules Chemical class 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- 230000009385 viral infection Effects 0.000 description 7
- 108020004638 Circular DNA Proteins 0.000 description 6
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 6
- 201000010099 disease Diseases 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- 239000003623 enhancer Substances 0.000 description 6
- 238000012239 gene modification Methods 0.000 description 6
- 230000005017 genetic modification Effects 0.000 description 6
- 235000013617 genetically modified food Nutrition 0.000 description 6
- 238000005259 measurement Methods 0.000 description 6
- 108020004999 messenger RNA Proteins 0.000 description 6
- 229920001184 polypeptide Polymers 0.000 description 6
- 230000002441 reversible effect Effects 0.000 description 6
- 241000894007 species Species 0.000 description 6
- 230000009261 transgenic effect Effects 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 5
- 231100000673 dose–response relationship Toxicity 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 239000003112 inhibitor Substances 0.000 description 5
- 230000003362 replicative effect Effects 0.000 description 5
- 230000008719 thickening Effects 0.000 description 5
- 241001529936 Murinae Species 0.000 description 4
- 229930193140 Neomycin Natural products 0.000 description 4
- 238000011529 RT qPCR Methods 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 238000010171 animal model Methods 0.000 description 4
- 230000001086 cytosolic effect Effects 0.000 description 4
- 210000004602 germ cell Anatomy 0.000 description 4
- 210000005260 human cell Anatomy 0.000 description 4
- 201000001421 hyperglycemia Diseases 0.000 description 4
- 229960004927 neomycin Drugs 0.000 description 4
- 238000006467 substitution reaction Methods 0.000 description 4
- 230000009466 transformation Effects 0.000 description 4
- 239000013598 vector Substances 0.000 description 4
- 230000004580 weight loss Effects 0.000 description 4
- NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 3
- 108091026890 Coding region Proteins 0.000 description 3
- 208000001528 Coronaviridae Infections Diseases 0.000 description 3
- 102000003779 Dipeptidyl-peptidases and tripeptidyl-peptidases Human genes 0.000 description 3
- 108090000194 Dipeptidyl-peptidases and tripeptidyl-peptidases Proteins 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 108091081024 Start codon Proteins 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 3
- 238000011156 evaluation Methods 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 208000024191 minimally invasive lung adenocarcinoma Diseases 0.000 description 3
- 230000003287 optical effect Effects 0.000 description 3
- 230000008506 pathogenesis Effects 0.000 description 3
- 230000002265 prevention Effects 0.000 description 3
- 238000011321 prophylaxis Methods 0.000 description 3
- 230000002685 pulmonary effect Effects 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 230000010076 replication Effects 0.000 description 3
- 238000010187 selection method Methods 0.000 description 3
- 241000701161 unidentified adenovirus Species 0.000 description 3
- 210000005166 vasculature Anatomy 0.000 description 3
- 108020004463 18S ribosomal RNA Proteins 0.000 description 2
- 101710169336 5'-deoxyadenosine deaminase Proteins 0.000 description 2
- NJYVEMPWNAYQQN-UHFFFAOYSA-N 5-carboxyfluorescein Chemical compound C12=CC=C(O)C=C2OC2=CC(O)=CC=C2C21OC(=O)C1=CC(C(=O)O)=CC=C21 NJYVEMPWNAYQQN-UHFFFAOYSA-N 0.000 description 2
- 238000011814 C57BL/6N mouse Methods 0.000 description 2
- 241000711573 Coronaviridae Species 0.000 description 2
- 108010051219 Cre recombinase Proteins 0.000 description 2
- 108010067722 Dipeptidyl Peptidase 4 Proteins 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 241000315672 SARS coronavirus Species 0.000 description 2
- 241000555745 Sciuridae Species 0.000 description 2
- 101150084279 TM gene Proteins 0.000 description 2
- 230000004075 alteration Effects 0.000 description 2
- 125000000539 amino acid group Chemical group 0.000 description 2
- 230000003115 biocidal effect Effects 0.000 description 2
- 238000001574 biopsy Methods 0.000 description 2
- 230000002759 chromosomal effect Effects 0.000 description 2
- 238000010367 cloning Methods 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 238000001506 fluorescence spectroscopy Methods 0.000 description 2
- 238000003205 genotyping method Methods 0.000 description 2
- 238000007490 hematoxylin and eosin (H&E) staining Methods 0.000 description 2
- 238000007901 in situ hybridization Methods 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 210000004969 inflammatory cell Anatomy 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 238000011081 inoculation Methods 0.000 description 2
- 238000003780 insertion Methods 0.000 description 2
- 230000037431 insertion Effects 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 210000002540 macrophage Anatomy 0.000 description 2
- 238000010172 mouse model Methods 0.000 description 2
- 108091027963 non-coding RNA Proteins 0.000 description 2
- 102000042567 non-coding RNA Human genes 0.000 description 2
- 210000002381 plasma Anatomy 0.000 description 2
- 238000003752 polymerase chain reaction Methods 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 238000011714 129 mouse Methods 0.000 description 1
- 101150033839 4 gene Proteins 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
- 102000055025 Adenosine deaminases Human genes 0.000 description 1
- 208000010370 Adenoviridae Infections Diseases 0.000 description 1
- 206010060931 Adenovirus infection Diseases 0.000 description 1
- 125000001433 C-terminal amino-acid group Chemical group 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- 102000053602 DNA Human genes 0.000 description 1
- 102000002322 Egg Proteins Human genes 0.000 description 1
- 108010000912 Egg Proteins Proteins 0.000 description 1
- 241001481760 Erethizon dorsatum Species 0.000 description 1
- 102000018389 Exopeptidases Human genes 0.000 description 1
- 108010091443 Exopeptidases Proteins 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 102000004889 Interleukin-6 Human genes 0.000 description 1
- 108090001005 Interleukin-6 Proteins 0.000 description 1
- 102000010781 Interleukin-6 Receptors Human genes 0.000 description 1
- 108010038501 Interleukin-6 Receptors Proteins 0.000 description 1
- 208000029523 Interstitial Lung disease Diseases 0.000 description 1
- 241000581650 Ivesia Species 0.000 description 1
- 208000019693 Lung disease Diseases 0.000 description 1
- 240000008821 Menyanthes trifoliata Species 0.000 description 1
- 235000011779 Menyanthes trifoliata Nutrition 0.000 description 1
- 238000000636 Northern blotting Methods 0.000 description 1
- 238000013381 RNA quantification Methods 0.000 description 1
- 108091028664 Ribonucleotide Proteins 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 230000006044 T cell activation Effects 0.000 description 1
- 108700009124 Transcription Initiation Site Proteins 0.000 description 1
- 108091005956 Type II transmembrane proteins Proteins 0.000 description 1
- 108091023045 Untranslated Region Proteins 0.000 description 1
- 241001105470 Valenzuela Species 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 208000011589 adenoviridae infectious disease Diseases 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 230000008382 alveolar damage Effects 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 210000004507 artificial chromosome Anatomy 0.000 description 1
- 210000002459 blastocyst Anatomy 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 239000005547 deoxyribonucleotide Substances 0.000 description 1
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 230000008378 epithelial damage Effects 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 238000010195 expression analysis Methods 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 102000034287 fluorescent proteins Human genes 0.000 description 1
- 108091006047 fluorescent proteins Proteins 0.000 description 1
- -1 for example Proteins 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- ZJYYHGLJYGJLLN-UHFFFAOYSA-N guanidinium thiocyanate Chemical compound SC#N.NC(N)=N ZJYYHGLJYGJLLN-UHFFFAOYSA-N 0.000 description 1
- 238000010562 histological examination Methods 0.000 description 1
- 238000000265 homogenisation Methods 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 238000012966 insertion method Methods 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 230000010468 interferon response Effects 0.000 description 1
- 230000031146 intracellular signal transduction Effects 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 229960000318 kanamycin Drugs 0.000 description 1
- 229930027917 kanamycin Natural products 0.000 description 1
- SBUJHOSQTJFQJX-NOAMYHISSA-N kanamycin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N SBUJHOSQTJFQJX-NOAMYHISSA-N 0.000 description 1
- 229930182823 kanamycin A Natural products 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 210000004681 ovum Anatomy 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 231100000915 pathological change Toxicity 0.000 description 1
- 230000036285 pathological change Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 229940076372 protein antagonist Drugs 0.000 description 1
- 229940121649 protein inhibitor Drugs 0.000 description 1
- 238000001273 protein sequence alignment Methods 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 239000002336 ribonucleotide Substances 0.000 description 1
- 125000002652 ribonucleotide group Chemical group 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000002864 sequence alignment Methods 0.000 description 1
- 238000002626 targeted therapy Methods 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 238000010361 transduction Methods 0.000 description 1
- 230000026683 transduction Effects 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000010474 transient expression Effects 0.000 description 1
- 238000002834 transmittance Methods 0.000 description 1
- 230000010415 tropism Effects 0.000 description 1
- 230000009452 underexpressoin Effects 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
- 238000010200 validation analysis Methods 0.000 description 1
- 210000003501 vero cell Anatomy 0.000 description 1
- 230000029812 viral genome replication Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K67/00—Rearing or breeding animals, not otherwise provided for; New or modified breeds of animals
- A01K67/027—New or modified breeds of vertebrates
- A01K67/0275—Genetically modified vertebrates, e.g. transgenic
- A01K67/0278—Knock-in vertebrates, e.g. humanised vertebrates
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K67/00—Rearing or breeding animals, not otherwise provided for; New or modified breeds of animals
- A01K67/027—New or modified breeds of vertebrates
- A01K67/0275—Genetically modified vertebrates, e.g. transgenic
- A01K67/0276—Knock-out vertebrates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- 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
-
- 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
-
- 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
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0603—Embryonic cells ; Embryoid bodies
- C12N5/0606—Pluripotent embryonic cells, e.g. embryonic stem cells [ES]
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
- C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/70—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving virus or bacteriophage
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y304/00—Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
- C12Y304/14—Dipeptidyl-peptidases and tripeptidyl-peptidases (3.4.14)
- C12Y304/14005—Dipeptidyl-peptidase IV (3.4.14.5)
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/569—Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses
- G01N33/56983—Viruses
-
- 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
- A01K2217/07—Animals genetically altered by homologous recombination
- A01K2217/072—Animals genetically altered by homologous recombination maintaining or altering function, i.e. knock in
-
- 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
- A01K2227/105—Murine
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2267/00—Animals characterised by purpose
- A01K2267/01—Animal expressing industrially exogenous proteins
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2267/00—Animals characterised by purpose
- A01K2267/03—Animal model, e.g. for test or diseases
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2267/00—Animals characterised by purpose
- A01K2267/03—Animal model, e.g. for test or diseases
- A01K2267/0337—Animal models for infectious diseases
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Zoology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Wood Science & Technology (AREA)
- Biotechnology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- Immunology (AREA)
- Molecular Biology (AREA)
- Environmental Sciences (AREA)
- Analytical Chemistry (AREA)
- Microbiology (AREA)
- Biomedical Technology (AREA)
- Physics & Mathematics (AREA)
- Biophysics (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Virology (AREA)
- Biodiversity & Conservation Biology (AREA)
- Animal Husbandry (AREA)
- Pathology (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Medicinal Chemistry (AREA)
- Cell Biology (AREA)
- Diabetes (AREA)
- Tropical Medicine & Parasitology (AREA)
- Food Science & Technology (AREA)
- General Physics & Mathematics (AREA)
- Developmental Biology & Embryology (AREA)
- Gynecology & Obstetrics (AREA)
- Reproductive Health (AREA)
- Plant Pathology (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201462005476P | 2014-05-30 | 2014-05-30 | |
| US201462051626P | 2014-09-17 | 2014-09-17 | |
| US201462072692P | 2014-10-30 | 2014-10-30 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2877275T3 true ES2877275T3 (es) | 2021-11-16 |
Family
ID=53366330
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES18173004T Active ES2877275T3 (es) | 2014-05-30 | 2015-05-28 | Animales con dipeptidil peptidasa IV (DPP4) humanizada |
| ES15727832T Active ES2691529T3 (es) | 2014-05-30 | 2015-05-28 | Animales con dipeptidil peptidasa iv (dpp4) humanizada |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES15727832T Active ES2691529T3 (es) | 2014-05-30 | 2015-05-28 | Animales con dipeptidil peptidasa iv (dpp4) humanizada |
Country Status (16)
| Country | Link |
|---|---|
| US (5) | US9497945B2 (enExample) |
| EP (2) | EP3381279B1 (enExample) |
| JP (2) | JP6212659B2 (enExample) |
| KR (1) | KR101737432B1 (enExample) |
| CN (2) | CN106413394B (enExample) |
| AU (1) | AU2015266841C1 (enExample) |
| BR (1) | BR112016026245A2 (enExample) |
| CA (1) | CA2947899C (enExample) |
| ES (2) | ES2877275T3 (enExample) |
| IL (1) | IL248702B (enExample) |
| MX (2) | MX373055B (enExample) |
| NZ (1) | NZ726355A (enExample) |
| PH (1) | PH12016502170A1 (enExample) |
| RU (1) | RU2648166C1 (enExample) |
| SG (1) | SG11201609154TA (enExample) |
| WO (1) | WO2015184164A1 (enExample) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JO3701B1 (ar) * | 2014-05-23 | 2021-01-31 | Regeneron Pharma | مضادات حيوية بشرية لمتلازمة الشرق الأوسط التنفسية - بروتين كورونا فيروس الشوكي |
| BR112016026245A2 (pt) | 2014-05-30 | 2018-02-20 | Regeneron Pharma | ?roedor, e, métodos para fazer um roedor humanizado, para fazer um camundongo com dpp4 humanizado, para fazer um roedor transgênico humanizado e para determinar a eficácia terapêutica in vivo de um antagonista da dpp4 específica para humanos no roedor? |
| EP3585162B1 (en) * | 2017-09-29 | 2023-08-30 | Regeneron Pharmaceuticals, Inc. | Rodents comprising a humanized ttr locus and methods of use |
| CN109022489B (zh) * | 2018-08-09 | 2023-03-31 | 中国食品药品检定研究院 | 人dpp4基因敲入的小鼠模型、其产生方法和用途 |
| EP3927153A1 (en) | 2019-02-22 | 2021-12-29 | Regeneron Pharmaceuticals, Inc. | Rodents having genetically modified sodium channels and methods of use thereof |
| JP2023511626A (ja) * | 2020-01-28 | 2023-03-20 | リジェネロン・ファーマシューティカルズ・インコーポレイテッド | ヒト化ｐｎｐｌａ３遺伝子座を含む非ヒト動物および使用方法 |
| KR102207249B1 (ko) * | 2020-02-28 | 2021-01-25 | 대한민국(관리청: 특허청장, 승계청: 질병관리청장) | 한국형 중동호흡기증후군 코로나바이러스 감염에 감수성을 가지는 인간 dpp4 유전자를 전신에 발현하는 형질전환마우스와 이의 용도 |
| KR102243416B1 (ko) * | 2020-02-28 | 2021-04-22 | 대한민국(질병관리청장) | 한국형 중동호흡기증후군 코로나바이러스 감염에 감수성을 가지는 인간 dpp4 유전자를 폐 조직 특이적으로 발현하는 형질전환마우스와 이의 용도 |
| CN113355325B (zh) * | 2020-03-06 | 2023-07-14 | 中国科学院广州生物医药与健康研究院 | 人源化ace2基因改造小鼠胚胎干细胞模型制备方法及应用 |
| WO2021263146A2 (en) * | 2020-06-26 | 2021-12-30 | Regeneron Pharmaceuticals, Inc. | Non-human animals comprising a humanized ace2 locus |
| WO2024124111A1 (en) * | 2022-12-08 | 2024-06-13 | The Regents Of The University Of California | Multimeric protein complexes for neutralization of viral pathogens in diagnostic, prophylactic, and therapeutic applications |
Family Cites Families (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6368604B1 (en) * | 1997-09-26 | 2002-04-09 | University Of Maryland Biotechnology Institute | Non-pyrogenic derivatives of lipid A |
| WO2002006630A1 (en) | 2000-07-18 | 2002-01-24 | The Charles Machine Works, Inc. | Apparatus and method for maintaining control of a drilling machine |
| US6586251B2 (en) | 2000-10-31 | 2003-07-01 | Regeneron Pharmaceuticals, Inc. | Methods of modifying eukaryotic cells |
| US20050144655A1 (en) | 2000-10-31 | 2005-06-30 | Economides Aris N. | Methods of modifying eukaryotic cells |
| US6596541B2 (en) * | 2000-10-31 | 2003-07-22 | Regeneron Pharmaceuticals, Inc. | Methods of modifying eukaryotic cells |
| EP1631680A2 (en) * | 2003-05-21 | 2006-03-08 | Bayer HealthCare AG | Diagnostics and therapeutics for diseases associated with dipeptidylpeptidase iv (dpp4) |
| EP1802193B1 (en) | 2004-10-19 | 2014-04-30 | Regeneron Pharmaceuticals, Inc. | Method for generating a mouse homozygous for a genetic modification |
| US20060272038A1 (en) | 2005-05-27 | 2006-11-30 | Michael De Vivo | Transgenic Alzheimer's mouse model vectors and uses thereof |
| US8110720B2 (en) * | 2006-12-22 | 2012-02-07 | Genentech, Inc | Transgenic mice expressing humanized VEGF |
| WO2010110914A2 (en) * | 2009-03-27 | 2010-09-30 | Zirus, Inc. | Mammalian genes involved in infection |
| EP3336102A3 (en) | 2009-12-21 | 2018-08-01 | Regeneron Pharmaceuticals, Inc. | Humanized fc gamma r mice |
| CN105950654B (zh) * | 2010-11-27 | 2020-03-20 | 朱坚 | 一种人源化的转基因动物 |
| RU2577978C2 (ru) * | 2011-02-15 | 2016-03-20 | Ридженерон Фармасьютикалз, Инк. | Гуманизированные m-csf мыши |
| RU2751240C2 (ru) * | 2011-10-28 | 2021-07-12 | Регенерон Фармасьютикалс, Инк. | Гуманизированные il-6 и рецептор il-6 |
| WO2014045254A2 (en) * | 2012-09-23 | 2014-03-27 | Erasmus University Medical Center Rotterdam | Human betacoronavirus lineage c and identification of n-terminal dipeptidyl peptidase as its virus receptor |
| JP6475172B2 (ja) | 2013-02-20 | 2019-02-27 | リジェネロン・ファーマシューティカルズ・インコーポレイテッドＲｅｇｅｎｅｒｏｎ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． | ラットの遺伝子組換え |
| EP3456831B1 (en) | 2013-04-16 | 2021-07-14 | Regeneron Pharmaceuticals, Inc. | Targeted modification of rat genome |
| CN103554235B (zh) * | 2013-06-17 | 2015-06-24 | 清华大学 | MERS-CoV病毒膜蛋白中的RBD片段及其编码基因和应用 |
| CN103724406A (zh) * | 2013-11-20 | 2014-04-16 | 中国疾病预防控制中心病毒病预防控制所 | 一种具有中和活性的MERS-CoV合成肽疫苗及其应用 |
| MX388127B (es) * | 2013-12-11 | 2025-03-19 | Regeneron Pharma | Metodos y composiciones para la modificacion dirigida de un genoma. |
| BR112016026245A2 (pt) | 2014-05-30 | 2018-02-20 | Regeneron Pharma | ?roedor, e, métodos para fazer um roedor humanizado, para fazer um camundongo com dpp4 humanizado, para fazer um roedor transgênico humanizado e para determinar a eficácia terapêutica in vivo de um antagonista da dpp4 específica para humanos no roedor? |
-
2015
- 2015-05-28 BR BR112016026245A patent/BR112016026245A2/pt not_active IP Right Cessation
- 2015-05-28 WO PCT/US2015/033024 patent/WO2015184164A1/en not_active Ceased
- 2015-05-28 MX MX2016015609A patent/MX373055B/es active IP Right Grant
- 2015-05-28 AU AU2015266841A patent/AU2015266841C1/en active Active
- 2015-05-28 CA CA2947899A patent/CA2947899C/en active Active
- 2015-05-28 JP JP2016566982A patent/JP6212659B2/ja active Active
- 2015-05-28 EP EP18173004.5A patent/EP3381279B1/en active Active
- 2015-05-28 SG SG11201609154TA patent/SG11201609154TA/en unknown
- 2015-05-28 RU RU2016150679A patent/RU2648166C1/ru active
- 2015-05-28 MX MX2020004803A patent/MX387036B/es unknown
- 2015-05-28 CN CN201580027887.6A patent/CN106413394B/zh active Active
- 2015-05-28 CN CN202010059426.XA patent/CN111118047B/zh active Active
- 2015-05-28 US US14/723,855 patent/US9497945B2/en active Active
- 2015-05-28 ES ES18173004T patent/ES2877275T3/es active Active
- 2015-05-28 ES ES15727832T patent/ES2691529T3/es active Active
- 2015-05-28 NZ NZ726355A patent/NZ726355A/en not_active IP Right Cessation
- 2015-05-28 KR KR1020167031766A patent/KR101737432B1/ko not_active Expired - Fee Related
- 2015-05-28 EP EP15727832.6A patent/EP2993977B1/en active Active
- 2015-08-12 US US14/824,475 patent/US9532555B2/en active Active
-
2016
- 2016-10-17 US US15/295,955 patent/US10212923B2/en active Active
- 2016-11-02 IL IL248702A patent/IL248702B/en active IP Right Grant
- 2016-11-02 PH PH12016502170A patent/PH12016502170A1/en unknown
-
2017
- 2017-09-15 JP JP2017177761A patent/JP6636486B2/ja active Active
-
2019
- 2019-01-03 US US16/239,028 patent/US11013220B2/en active Active
-
2021
- 2021-04-21 US US17/236,083 patent/US12256720B2/en active Active
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2877275T3 (es) | Animales con dipeptidil peptidasa IV (DPP4) humanizada | |
| ES2656529T3 (es) | Animales con IL-4 e IL-4R alfa humanizadas | |
| CN110951745A (zh) | Cd163突变基因及其在抑制或阻断猪产生抗体的方法和应用 | |
| WO2022232348A1 (en) | Angiotensin-converting enzyme ii (ace2) transgenic animal and uses thereof | |
| CN106554954B (zh) | 一种ev71疫苗的体内效力评价方法及抗病毒药物筛选方法 | |
| HK1257297B (en) | Humanized dipeptidyl peptidase iv (dpp4) animals | |
| HK1216822B (en) | Humanized dipeptidyl peptidase iv (dpp4) animals | |
| CN115279184A (zh) | B4galt1介导的功能的啮齿动物模型 | |
| An et al. | A transgenic mouse line with a 58-kb fragment deletion in chromosome 11E1 that encompasses part of the Fam20a gene and its upstream region shows growth disorder | |
| KR20250169390A (ko) | 인간 ace2 및 tmprss2 유전자를 발현하는 형질전환마우스와 이의 용도 | |
| Tucker | Inborn Errors of Metabolism II | |
| CN117721152A (zh) | Ttp在制备骨关节炎药物中的应用 |