CA3162639A1 - A murine model of fetal/neonatal alloimmune thrombocytopenia - Google Patents
A murine model of fetal/neonatal alloimmune thrombocytopeniaInfo
- Publication number
- CA3162639A1 CA3162639A1 CA3162639A CA3162639A CA3162639A1 CA 3162639 A1 CA3162639 A1 CA 3162639A1 CA 3162639 A CA3162639 A CA 3162639A CA 3162639 A CA3162639 A CA 3162639A CA 3162639 A1 CA3162639 A1 CA 3162639A1
- Authority
- CA
- Canada
- Prior art keywords
- gpiiia
- mouse
- hpa
- antibody
- seq
- 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.)
- Pending
Links
- 230000001605 fetal effect Effects 0.000 title claims description 39
- 208000009567 Neonatal Alloimmune Thrombocytopenia Diseases 0.000 title description 11
- 238000010172 mouse model Methods 0.000 title description 4
- 108010020950 Integrin beta3 Proteins 0.000 claims abstract description 151
- 238000000034 method Methods 0.000 claims abstract description 86
- 230000035772 mutation Effects 0.000 claims abstract description 76
- 238000012360 testing method Methods 0.000 claims abstract description 53
- 102200128633 rs104893843 Human genes 0.000 claims abstract description 49
- 238000011830 transgenic mouse model Methods 0.000 claims abstract description 46
- 102220131569 rs759461234 Human genes 0.000 claims abstract description 15
- 102220562539 Angiotensin-converting enzyme_S32P_mutation Human genes 0.000 claims abstract description 14
- 241000699666 Mus <mouse, genus> Species 0.000 claims description 107
- 241001529936 Murinae Species 0.000 claims description 70
- 101001015004 Homo sapiens Integrin beta-3 Proteins 0.000 claims description 45
- 230000034431 double-strand break repair via homologous recombination Effects 0.000 claims description 44
- 102100032999 Integrin beta-3 Human genes 0.000 claims description 39
- 108091033409 CRISPR Proteins 0.000 claims description 36
- 102220504838 Choline transporter-like protein 4_N29D_mutation Human genes 0.000 claims description 33
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 26
- 239000000427 antigen Substances 0.000 claims description 24
- 108091007433 antigens Proteins 0.000 claims description 22
- 102000036639 antigens Human genes 0.000 claims description 22
- 108020005004 Guide RNA Proteins 0.000 claims description 21
- 241000699670 Mus sp. Species 0.000 claims description 20
- 230000000740 bleeding effect Effects 0.000 claims description 20
- 230000035935 pregnancy Effects 0.000 claims description 20
- 108091034117 Oligonucleotide Proteins 0.000 claims description 19
- 239000002773 nucleotide Substances 0.000 claims description 18
- 125000003729 nucleotide group Chemical group 0.000 claims description 18
- 239000000758 substrate Substances 0.000 claims description 17
- 230000004044 response Effects 0.000 claims description 13
- 230000037432 silent mutation Effects 0.000 claims description 12
- 102000039446 nucleic acids Human genes 0.000 claims description 10
- 108020004707 nucleic acids Proteins 0.000 claims description 10
- 150000007523 nucleic acids Chemical class 0.000 claims description 10
- 210000000287 oocyte Anatomy 0.000 claims description 10
- 238000012216 screening Methods 0.000 claims description 10
- 230000008685 targeting Effects 0.000 claims description 10
- 238000001727 in vivo Methods 0.000 claims description 9
- 108700039855 mouse a Proteins 0.000 claims description 9
- 230000029087 digestion Effects 0.000 claims description 8
- 238000000338 in vitro Methods 0.000 claims description 8
- 101710163270 Nuclease Proteins 0.000 claims description 7
- 238000003556 assay Methods 0.000 claims description 7
- 239000011324 bead Substances 0.000 claims description 7
- 230000002829 reductive effect Effects 0.000 claims description 7
- 230000003252 repetitive effect Effects 0.000 claims description 7
- 239000000523 sample Substances 0.000 claims description 7
- 210000000805 cytoplasm Anatomy 0.000 claims description 6
- 210000002826 placenta Anatomy 0.000 claims description 6
- 210000003101 oviduct Anatomy 0.000 claims description 4
- 101100113065 Mus musculus Cfi gene Proteins 0.000 claims description 3
- 210000002257 embryonic structure Anatomy 0.000 claims description 3
- 239000012528 membrane Substances 0.000 claims description 3
- 239000002245 particle Substances 0.000 claims description 3
- 239000011347 resin Substances 0.000 claims description 3
- 229920005989 resin Polymers 0.000 claims description 3
- 102200067132 rs3219484 Human genes 0.000 claims description 2
- 102000008607 Integrin beta3 Human genes 0.000 abstract description 142
- 150000001875 compounds Chemical class 0.000 abstract description 5
- 235000001014 amino acid Nutrition 0.000 description 55
- 150000001413 amino acids Chemical class 0.000 description 37
- 208000017118 fetal and neonatal alloimmune thrombocytopenia Diseases 0.000 description 37
- 101000880344 Homo sapiens Elongation factor G, mitochondrial Proteins 0.000 description 30
- 208000015228 acquired partial lipodystrophy Diseases 0.000 description 30
- 102100037642 Elongation factor G, mitochondrial Human genes 0.000 description 29
- 210000004027 cell Anatomy 0.000 description 25
- 238000006467 substitution reaction Methods 0.000 description 24
- 108090000623 proteins and genes Proteins 0.000 description 21
- 208000032843 Hemorrhage Diseases 0.000 description 19
- 208000034158 bleeding Diseases 0.000 description 18
- 230000008774 maternal effect Effects 0.000 description 18
- 241001465754 Metazoa Species 0.000 description 17
- 210000004369 blood Anatomy 0.000 description 17
- 239000008280 blood Substances 0.000 description 17
- 102100030802 Beta-2-glycoprotein 1 Human genes 0.000 description 15
- 101000793425 Homo sapiens Beta-2-glycoprotein 1 Proteins 0.000 description 15
- 102000015795 Platelet Membrane Glycoproteins Human genes 0.000 description 15
- 108010010336 Platelet Membrane Glycoproteins Proteins 0.000 description 15
- 102000006495 integrins Human genes 0.000 description 15
- 108010044426 integrins Proteins 0.000 description 15
- 208000003441 Transfusion reaction Diseases 0.000 description 14
- 230000009261 transgenic effect Effects 0.000 description 14
- 239000013612 plasmid Substances 0.000 description 13
- 102000004169 proteins and genes Human genes 0.000 description 12
- 239000012634 fragment Substances 0.000 description 11
- 235000018102 proteins Nutrition 0.000 description 11
- YQNRVGJCPCNMKT-LFVJCYFKSA-N 2-[(e)-[[2-(4-benzylpiperazin-1-ium-1-yl)acetyl]hydrazinylidene]methyl]-6-prop-2-enylphenolate Chemical compound [O-]C1=C(CC=C)C=CC=C1\C=N\NC(=O)C[NH+]1CCN(CC=2C=CC=CC=2)CC1 YQNRVGJCPCNMKT-LFVJCYFKSA-N 0.000 description 10
- 101000838335 Homo sapiens Dual specificity protein phosphatase 2 Proteins 0.000 description 10
- 101001080401 Homo sapiens Proteasome assembly chaperone 1 Proteins 0.000 description 10
- 229960005552 PAC-1 Drugs 0.000 description 10
- 102100027583 Proteasome assembly chaperone 1 Human genes 0.000 description 10
- 238000000684 flow cytometry Methods 0.000 description 10
- 108090000765 processed proteins & peptides Proteins 0.000 description 10
- 230000000961 alloantigen Effects 0.000 description 9
- 238000003032 molecular docking Methods 0.000 description 9
- 102000004196 processed proteins & peptides Human genes 0.000 description 9
- 206010043554 thrombocytopenia Diseases 0.000 description 9
- 238000010354 CRISPR gene editing Methods 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 108010029485 Protein Isoforms Proteins 0.000 description 7
- 102000001708 Protein Isoforms Human genes 0.000 description 7
- 230000002441 reversible effect Effects 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- 238000011282 treatment Methods 0.000 description 7
- 108020004414 DNA Proteins 0.000 description 6
- 238000002965 ELISA Methods 0.000 description 6
- 102000003886 Glycoproteins Human genes 0.000 description 6
- 108090000288 Glycoproteins Proteins 0.000 description 6
- 206010050455 Refractoriness to platelet transfusion Diseases 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 6
- 230000001404 mediated effect Effects 0.000 description 6
- 241000283707 Capra Species 0.000 description 5
- 101001078143 Homo sapiens Integrin alpha-IIb Proteins 0.000 description 5
- 238000012300 Sequence Analysis Methods 0.000 description 5
- 125000000539 amino acid group Chemical group 0.000 description 5
- 238000009395 breeding Methods 0.000 description 5
- 230000001488 breeding effect Effects 0.000 description 5
- 229920001184 polypeptide Polymers 0.000 description 5
- 230000009257 reactivity Effects 0.000 description 5
- 102200159310 rs28936077 Human genes 0.000 description 5
- 238000001890 transfection Methods 0.000 description 5
- 239000013598 vector Substances 0.000 description 5
- 108700028369 Alleles Proteins 0.000 description 4
- 238000011740 C57BL/6 mouse Methods 0.000 description 4
- 238000011814 C57BL/6N mouse Methods 0.000 description 4
- 206010018985 Haemorrhage intracranial Diseases 0.000 description 4
- 208000008574 Intracranial Hemorrhages Diseases 0.000 description 4
- 108091028043 Nucleic acid sequence Proteins 0.000 description 4
- 108700019146 Transgenes Proteins 0.000 description 4
- 208000037927 alloimmune thrombocytopaenia Diseases 0.000 description 4
- 238000003776 cleavage reaction Methods 0.000 description 4
- 108010048367 enhanced green fluorescent protein Proteins 0.000 description 4
- 210000003754 fetus Anatomy 0.000 description 4
- 230000028993 immune response Effects 0.000 description 4
- 230000003053 immunization Effects 0.000 description 4
- 238000002649 immunization Methods 0.000 description 4
- 230000013011 mating Effects 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 230000000069 prophylactic effect Effects 0.000 description 4
- 241000894007 species Species 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- 206010060935 Alloimmunisation Diseases 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- 101150044523 ITGB3 gene Proteins 0.000 description 3
- 102100025306 Integrin alpha-IIb Human genes 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- -1 aromatic amino acids Chemical class 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 235000013601 eggs Nutrition 0.000 description 3
- 230000002209 hydrophobic effect Effects 0.000 description 3
- 238000003018 immunoassay Methods 0.000 description 3
- 238000010348 incorporation Methods 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 210000001161 mammalian embryo Anatomy 0.000 description 3
- 238000013507 mapping Methods 0.000 description 3
- 239000011159 matrix material Substances 0.000 description 3
- 238000002823 phage display Methods 0.000 description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
- 239000013615 primer Substances 0.000 description 3
- 238000010403 protein-protein docking Methods 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 238000012552 review Methods 0.000 description 3
- 238000012163 sequencing technique Methods 0.000 description 3
- 238000002741 site-directed mutagenesis Methods 0.000 description 3
- 230000003582 thrombocytopenic effect Effects 0.000 description 3
- 101150072006 33 gene Proteins 0.000 description 2
- 208000031261 Acute myeloid leukaemia Diseases 0.000 description 2
- 239000012114 Alexa Fluor 647 Substances 0.000 description 2
- 108010032595 Antibody Binding Sites Proteins 0.000 description 2
- 102000009024 Epidermal Growth Factor Human genes 0.000 description 2
- 102000008946 Fibrinogen Human genes 0.000 description 2
- 108010049003 Fibrinogen Proteins 0.000 description 2
- 208000009329 Graft vs Host Disease Diseases 0.000 description 2
- 102100040482 HLA class II histocompatibility antigen, DR beta 3 chain Human genes 0.000 description 2
- 108010061311 HLA-DRB3 Chains Proteins 0.000 description 2
- 108700018351 Major Histocompatibility Complex Proteins 0.000 description 2
- 108010085220 Multiprotein Complexes Proteins 0.000 description 2
- 102000007474 Multiprotein Complexes Human genes 0.000 description 2
- 101001015002 Mus musculus Integrin beta-3 Proteins 0.000 description 2
- 101100174574 Mus musculus Pikfyve gene Proteins 0.000 description 2
- 210000001744 T-lymphocyte Anatomy 0.000 description 2
- 208000012346 Venoocclusive disease Diseases 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 238000001994 activation Methods 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 210000003719 b-lymphocyte Anatomy 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 239000003599 detergent Substances 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- 238000002224 dissection Methods 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000013604 expression vector Substances 0.000 description 2
- 229940012952 fibrinogen Drugs 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
- 238000002866 fluorescence resonance energy transfer Methods 0.000 description 2
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 208000024908 graft versus host disease Diseases 0.000 description 2
- 208000031169 hemorrhagic disease Diseases 0.000 description 2
- 230000008348 humoral response Effects 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 230000010354 integration Effects 0.000 description 2
- 238000011835 investigation Methods 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 238000007726 management method Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 2
- 238000000520 microinjection Methods 0.000 description 2
- 239000011859 microparticle Substances 0.000 description 2
- 238000000302 molecular modelling Methods 0.000 description 2
- 208000030372 neonatal thrombocytopenia Diseases 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 229940046166 oligodeoxynucleotide Drugs 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 238000003127 radioimmunoassay Methods 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 238000007423 screening assay Methods 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 150000003384 small molecules Chemical class 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 230000020382 suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I Effects 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
- 101710132383 66 kDa protein Proteins 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 229920000936 Agarose Polymers 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 238000010453 CRISPR/Cas method Methods 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 108020004705 Codon Proteins 0.000 description 1
- 208000034656 Contusions Diseases 0.000 description 1
- 239000003155 DNA primer Substances 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102400001368 Epidermal growth factor Human genes 0.000 description 1
- 101800003838 Epidermal growth factor Proteins 0.000 description 1
- 108091029865 Exogenous DNA Proteins 0.000 description 1
- 108010012088 Fibrinogen Receptors Proteins 0.000 description 1
- 206010055690 Foetal death Diseases 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- 108010044091 Globulins Proteins 0.000 description 1
- 102000006395 Globulins Human genes 0.000 description 1
- 101000878605 Homo sapiens Low affinity immunoglobulin epsilon Fc receptor Proteins 0.000 description 1
- 102000008100 Human Serum Albumin Human genes 0.000 description 1
- 108091006905 Human Serum Albumin Proteins 0.000 description 1
- 208000028622 Immune thrombocytopenia Diseases 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 102000004195 Isomerases Human genes 0.000 description 1
- 108090000769 Isomerases Proteins 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- 239000012097 Lipofectamine 2000 Substances 0.000 description 1
- 208000035752 Live birth Diseases 0.000 description 1
- 102100038007 Low affinity immunoglobulin epsilon Fc receptor Human genes 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 102000012750 Membrane Glycoproteins Human genes 0.000 description 1
- 108010090054 Membrane Glycoproteins Proteins 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 101100460719 Mus musculus Noto gene Proteins 0.000 description 1
- 108010021466 Mutant Proteins Proteins 0.000 description 1
- 102000008300 Mutant Proteins Human genes 0.000 description 1
- GHAZCVNUKKZTLG-UHFFFAOYSA-N N-ethyl-succinimide Natural products CCN1C(=O)CCC1=O GHAZCVNUKKZTLG-UHFFFAOYSA-N 0.000 description 1
- HDFGOPSGAURCEO-UHFFFAOYSA-N N-ethylmaleimide Chemical compound CCN1C(=O)C=CC1=O HDFGOPSGAURCEO-UHFFFAOYSA-N 0.000 description 1
- 125000000729 N-terminal amino-acid group Chemical group 0.000 description 1
- 239000012124 Opti-MEM Substances 0.000 description 1
- 238000012408 PCR amplification Methods 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 108010067902 Peptide Library Proteins 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
- 206010037549 Purpura Diseases 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 108700008625 Reporter Genes Proteins 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 102000014105 Semaphorin Human genes 0.000 description 1
- 108050003978 Semaphorin Proteins 0.000 description 1
- 206010040047 Sepsis Diseases 0.000 description 1
- 206010041660 Splenomegaly Diseases 0.000 description 1
- 101100226845 Strongylocentrotus purpuratus EGF2 gene Proteins 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- 108091027544 Subgenomic mRNA Proteins 0.000 description 1
- JDZPLYBLBIKFHJ-UHFFFAOYSA-N Sulfamoyldapsone Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=C1S(N)(=O)=O JDZPLYBLBIKFHJ-UHFFFAOYSA-N 0.000 description 1
- 230000005867 T cell response Effects 0.000 description 1
- 208000031981 Thrombocytopenic Idiopathic Purpura Diseases 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 241000009298 Trigla lyra Species 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 101150117115 V gene Proteins 0.000 description 1
- 241000269370 Xenopus <genus> Species 0.000 description 1
- 108010037096 Xenopus Proteins Proteins 0.000 description 1
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 1
- 229940124532 absorption promoter Drugs 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 239000008351 acetate buffer Substances 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000003044 adaptive effect Effects 0.000 description 1
- 101150063416 add gene Proteins 0.000 description 1
- 239000011543 agarose gel Substances 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 208000033571 alveolar capillary dysplasia with misalignment of pulmonary veins Diseases 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000692 anti-sense effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 238000013176 antiplatelet therapy Methods 0.000 description 1
- 201000003710 autoimmune thrombocytopenic purpura Diseases 0.000 description 1
- 235000013405 beer Nutrition 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- 238000012575 bio-layer interferometry Methods 0.000 description 1
- 230000006287 biotinylation Effects 0.000 description 1
- 238000007413 biotinylation Methods 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 235000013330 chicken meat Nutrition 0.000 description 1
- 230000035606 childbirth Effects 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000007979 citrate buffer Substances 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 238000002967 competitive immunoassay Methods 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 229960001334 corticosteroids Drugs 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000009849 deactivation Effects 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 210000004443 dendritic cell Anatomy 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 230000001066 destructive effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000012850 discrimination method Methods 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 208000009190 disseminated intravascular coagulation Diseases 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 125000002228 disulfide group Chemical group 0.000 description 1
- 230000005782 double-strand break Effects 0.000 description 1
- 238000009510 drug design Methods 0.000 description 1
- 238000007876 drug discovery Methods 0.000 description 1
- 229960001484 edetic acid Drugs 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 229940116977 epidermal growth factor Drugs 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 239000013613 expression plasmid Substances 0.000 description 1
- 238000012921 fluorescence analysis Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 238000010362 genome editing Methods 0.000 description 1
- 238000003205 genotyping method Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 210000003714 granulocyte Anatomy 0.000 description 1
- 230000003394 haemopoietic effect Effects 0.000 description 1
- 102000043652 human GFM1 Human genes 0.000 description 1
- 102000057154 human ITGB3 Human genes 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 229940027941 immunoglobulin g Drugs 0.000 description 1
- 238000003364 immunohistochemistry Methods 0.000 description 1
- 238000012750 in vivo screening Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 150000002484 inorganic compounds Chemical class 0.000 description 1
- 229910010272 inorganic material Inorganic materials 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 238000007917 intracranial administration Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 231100001046 intrauterine death Toxicity 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 239000012139 lysis buffer Substances 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 239000000696 magnetic material Substances 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 239000007922 nasal spray Substances 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 230000001123 neurodevelopmental effect Effects 0.000 description 1
- 230000009437 off-target effect Effects 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 238000003305 oral gavage Methods 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 150000002902 organometallic compounds Chemical class 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000001991 pathophysiological effect Effects 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 208000004594 persistent fetal circulation syndrome Diseases 0.000 description 1
- 206010034754 petechiae Diseases 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 102000002022 plexin Human genes 0.000 description 1
- 108050009312 plexin Proteins 0.000 description 1
- 210000001778 pluripotent stem cell Anatomy 0.000 description 1
- 229950008882 polysorbate Drugs 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 238000011533 pre-incubation Methods 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 230000004853 protein function Effects 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 230000000284 resting effect Effects 0.000 description 1
- 230000000452 restraining effect Effects 0.000 description 1
- 238000002864 sequence alignment Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000003381 solubilizing effect Effects 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 238000004350 spin decoupling difference spectroscopy Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 238000000547 structure data Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 201000003067 thrombocytopenia due to platelet alloimmunization Diseases 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 241001515965 unidentified phage Species 0.000 description 1
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 1
- 238000011179 visual inspection Methods 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 230000036266 weeks of gestation Effects 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
- 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
- A01K2267/03—Animal model, e.g. for test or diseases
- A01K2267/0306—Animal model for genetic diseases
- A01K2267/0325—Animal model for autoimmune 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
- A01K2267/035—Animal model for multifactorial diseases
- A01K2267/0387—Animal model for diseases of the immune system
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Environmental Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Biotechnology (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Health & Medical Sciences (AREA)
- Zoology (AREA)
- Animal Husbandry (AREA)
- Biodiversity & Conservation Biology (AREA)
- Engineering & Computer Science (AREA)
- Peptides Or Proteins (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/US2019/059869 WO2021091539A1 (en) | 2019-11-05 | 2019-11-05 | A murine model of fetal/neonatal alloimmune thrombocytopenia |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA3162639A1 true CA3162639A1 (en) | 2021-05-14 |
Family
ID=69159981
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA3162639A Pending CA3162639A1 (en) | 2019-11-05 | 2019-11-05 | A murine model of fetal/neonatal alloimmune thrombocytopenia |
Country Status (6)
| Country | Link |
|---|---|
| EP (1) | EP4054324A1 (ja) |
| JP (1) | JP2023500896A (ja) |
| CN (1) | CN114630579A (ja) |
| AU (1) | AU2019473345A1 (ja) |
| CA (1) | CA3162639A1 (ja) |
| WO (1) | WO2021091539A1 (ja) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2022381210A1 (en) * | 2021-11-08 | 2024-05-02 | Rallybio Ipa, Llc | ASSAYS FOR QUANTIFICATION OF ANTI-HPA-1a ANTIBODIES |
Family Cites Families (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US661108A (en) | 1899-12-04 | 1900-11-06 | Albert Schmitz | Manufacture of compound tubes. |
| US4873191A (en) | 1981-06-12 | 1989-10-10 | Ohio University | Genetic transformation of zygotes |
| US4870009A (en) | 1982-11-22 | 1989-09-26 | The Salk Institute For Biological Studies | Method of obtaining gene product through the generation of transgenic animals |
| US4736866B1 (en) | 1984-06-22 | 1988-04-12 | Transgenic non-human mammals | |
| US4873316A (en) | 1987-06-23 | 1989-10-10 | Biogen, Inc. | Isolation of exogenous recombinant proteins from the milk of transgenic mammals |
| AU6505690A (en) | 1989-09-26 | 1991-04-28 | Richard R Behringer | Erythroid-specific gene expression system |
| DE4000939A1 (de) | 1990-01-15 | 1991-07-18 | Brem Gottfried Prof Dr Dr | Verfahren zur antikoerpergewinnung |
| AU1228592A (en) | 1991-01-11 | 1992-08-17 | American Red Cross | Expression of active human protein c in mammary tissue of transgenic animals |
| US6331658B1 (en) | 1993-04-20 | 2001-12-18 | Integris Baptist Medical Center, Inc. | Genetically engineered mammals for use as organ donors |
| US5639940A (en) | 1994-03-03 | 1997-06-17 | Pharmaceutical Proteins Ltd. | Production of fibrinogen in transgenic animals |
| US6204431B1 (en) | 1994-03-09 | 2001-03-20 | Abbott Laboratories | Transgenic non-human mammals expressing heterologous glycosyltransferase DNA sequences produce oligosaccharides and glycoproteins in their milk |
| US5959171A (en) | 1994-08-17 | 1999-09-28 | Pharming B.V. | Method for the production of biologically active polypeptides in a mammal's |
| US5880327A (en) | 1994-09-21 | 1999-03-09 | American National Red Cross | Transgenic mammals expressing human coagulation factor VIII |
| WO1996023882A1 (en) * | 1995-01-31 | 1996-08-08 | The Rockefeller University | IDENTIFICATION OF DEC, (DENTRITIC AND EPITHELIAL CELLS, 205 kDa), A RECEPTOR WITH C-TYPE LECTIN DOMAINS, NUCLEIC ACIDS ENCODING DEC, AND USES THEREOF |
| US6339183B1 (en) | 1995-06-05 | 2002-01-15 | New York University | Transgenic mammals expressing heterologous DNA in urothelium and isolation of biologically active molecules from urine |
| US6166288A (en) | 1995-09-27 | 2000-12-26 | Nextran Inc. | Method of producing transgenic animals for xenotransplantation expressing both an enzyme masking or reducing the level of the gal epitope and a complement inhibitor |
| AU7385596A (en) | 1995-10-02 | 1997-04-28 | Duke University | Dopamine transporter knockout mice |
| US6066778A (en) * | 1996-11-06 | 2000-05-23 | The Regents Of The University Of Michigan | Transgenic mice expressing APC resistant factor V |
| EP0971724B1 (en) | 1997-02-14 | 2010-01-20 | American Red Cross | Expression of active human factor ix in mammary tissue of transgenic animals |
| CN1292638A (zh) | 1998-01-08 | 2001-04-25 | 第一制药株式会社 | 基因突变动物 |
| AU4951300A (en) | 1999-05-31 | 2000-12-18 | Chugai Research Institute For Molecular Medicine, Inc. | Lkb1 gene knockout animals |
| US10548302B2 (en) * | 2016-07-29 | 2020-02-04 | Regeneron Pharmaceuticals, Inc. | Fibrillin-1 mutations for modeling neonatal progeroid syndrome with congenital lipodystrophy |
| CN108794631A (zh) * | 2018-06-12 | 2018-11-13 | 广州血液中心 | 一种鼠源性抗鼠cd36单克隆抗体的制备方法 |
| CN110384074A (zh) * | 2019-07-15 | 2019-10-29 | 广州医科大学 | 一种Kir7.1基因失活的小鼠模型及其构建方法 |
-
2019
- 2019-11-05 AU AU2019473345A patent/AU2019473345A1/en active Pending
- 2019-11-05 WO PCT/US2019/059869 patent/WO2021091539A1/en unknown
- 2019-11-05 EP EP19835940.8A patent/EP4054324A1/en active Pending
- 2019-11-05 CA CA3162639A patent/CA3162639A1/en active Pending
- 2019-11-05 JP JP2022526031A patent/JP2023500896A/ja active Pending
- 2019-11-05 CN CN201980101996.6A patent/CN114630579A/zh active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| JP2023500896A (ja) | 2023-01-11 |
| CN114630579A (zh) | 2022-06-14 |
| WO2021091539A1 (en) | 2021-05-14 |
| EP4054324A1 (en) | 2022-09-14 |
| AU2019473345A1 (en) | 2022-05-05 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US9686971B2 (en) | Methods for testing anti-thrombotic agents | |
| JP5315489B2 (ja) | エフェクター機能が増強されたヒトＩｇＧ抗体を作製する方法 | |
| CA2730063C (en) | Anti-baffr antibodies, compositions and processes for production thereof | |
| CN105861548B (zh) | Adam6小鼠 | |
| Zhi et al. | High-resolution mapping of the polyclonal immune response to the human platelet alloantigen HPA-1a (PlA1) | |
| US10725041B2 (en) | Method to bioengineer designer platelets using gene editing and stem cell methodologies | |
| JP2020078350A (ja) | ヒスチジン操作軽鎖抗体およびそれを生成するための遺伝子改変非ヒト動物 | |
| Zhang et al. | CRISPR/Cas9-mediated conversion of human platelet alloantigen allotypes | |
| JP2017505127A (ja) | 抗体親和性の最適化のための高スループットマウスモデル | |
| WO2003104270A2 (en) | Dudulin 2 genes, expression products, non-human animal model: uses in human hematological disease | |
| JP2017510273A (ja) | 異なる結合特性を示すｖｌ抗原結合タンパク質 | |
| JP2024091951A (ja) | 操作された重鎖可変領域を有する齧歯類 | |
| CA3162639A1 (en) | A murine model of fetal/neonatal alloimmune thrombocytopenia | |
| Watkins et al. | HPA-1a phenotype–genotype discrepancy reveals a naturally occurring Arg93Gln substitution in the platelet β3 integrin that disrupts the HPA-1a epitope | |
| US11266129B2 (en) | Murine model of fetal/neonatal alloimmune thrombocytopenia | |
| JP2020535815A (ja) | ヒト化Ｃ１ｑ複合体を発現する非ヒト動物 | |
| Morton et al. | Cloning and characterization of equine CD89 and identification of the CD89 gene in chimpanzees and rhesus macaques | |
| US20090317413A1 (en) | Detection of human platelet antigen (hpa) antibodies | |
| Chapel‐Fernandes et al. | Dombrock genotyping in a native Congolese cohort reveals two novel alleles | |
| US20200332259A1 (en) | Method to bioengineer designer red blood cells using gene editing and stem cell methodologies | |
| JP2005245337A (ja) | ニワトリ−ヒトキメラ抗体発現用ベクターおよびこれを用いたニワトリ−ヒトキメラ抗体生産方法、並びにその利用 | |
| Johnson | Predicting the Severity of Neonatal Alloimmune Thrombocytopenia through Risk Stratifcation by Assessing the IgG Subclasses Involved | |
| Oosterhoff et al. | Generation of human antibodies targeting human platelet antigen (HPA)‐1a | |
| Westhoff et al. | Rh, Kell, Duffy and Kidd antigens and antibodies | |
| Regev | Rapid CLIP dissociation from MHC II promotes an unusual antigen presentation pathway in autoimmunity |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |
Effective date: 20231026 |
|
| EEER | Examination request |
Effective date: 20231026 |
|
| EEER | Examination request |
Effective date: 20231026 |