CN113906048A - 通用供体干细胞和相关方法 - Google Patents
通用供体干细胞和相关方法 Download PDFInfo
- Publication number
- CN113906048A CN113906048A CN202080021860.7A CN202080021860A CN113906048A CN 113906048 A CN113906048 A CN 113906048A CN 202080021860 A CN202080021860 A CN 202080021860A CN 113906048 A CN113906048 A CN 113906048A
- Authority
- CN
- China
- Prior art keywords
- hla
- stem cell
- cell
- mhc
- expression
- 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
- 210000000130 stem cell Anatomy 0.000 title claims abstract description 261
- 238000000034 method Methods 0.000 title claims abstract description 81
- 210000004027 cell Anatomy 0.000 claims abstract description 259
- 230000014509 gene expression Effects 0.000 claims abstract description 215
- 239000000427 antigen Substances 0.000 claims abstract description 77
- 108091007433 antigens Proteins 0.000 claims abstract description 77
- 102000036639 antigens Human genes 0.000 claims abstract description 77
- 210000000265 leukocyte Anatomy 0.000 claims abstract description 76
- 230000003614 tolerogenic effect Effects 0.000 claims abstract description 63
- 108090000623 proteins and genes Proteins 0.000 claims description 159
- 102000004169 proteins and genes Human genes 0.000 claims description 133
- 229920002477 rna polymer Polymers 0.000 claims description 93
- 108010074708 B7-H1 Antigen Proteins 0.000 claims description 69
- 210000000822 natural killer cell Anatomy 0.000 claims description 68
- 102100028972 HLA class I histocompatibility antigen, A alpha chain Human genes 0.000 claims description 57
- 108010075704 HLA-A Antigens Proteins 0.000 claims description 57
- 102100028976 HLA class I histocompatibility antigen, B alpha chain Human genes 0.000 claims description 49
- 108010058607 HLA-B Antigens Proteins 0.000 claims description 49
- 108700002010 MHC class II transactivator Proteins 0.000 claims description 48
- 102100028967 HLA class I histocompatibility antigen, alpha chain G Human genes 0.000 claims description 46
- 108010024164 HLA-G Antigens Proteins 0.000 claims description 46
- 108010052199 HLA-C Antigens Proteins 0.000 claims description 44
- 102100028971 HLA class I histocompatibility antigen, C alpha chain Human genes 0.000 claims description 43
- 101000868279 Homo sapiens Leukocyte surface antigen CD47 Proteins 0.000 claims description 42
- 102100032913 Leukocyte surface antigen CD47 Human genes 0.000 claims description 42
- 210000002540 macrophage Anatomy 0.000 claims description 42
- 230000002829 reductive effect Effects 0.000 claims description 42
- 150000007523 nucleic acids Chemical group 0.000 claims description 34
- 230000000694 effects Effects 0.000 claims description 33
- 230000002163 immunogen Effects 0.000 claims description 29
- 108010058597 HLA-DR Antigens Proteins 0.000 claims description 27
- 102000006354 HLA-DR Antigens Human genes 0.000 claims description 27
- 101001000998 Homo sapiens Protein phosphatase 1 regulatory subunit 12C Proteins 0.000 claims description 27
- 102100035620 Protein phosphatase 1 regulatory subunit 12C Human genes 0.000 claims description 27
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 25
- 230000004069 differentiation Effects 0.000 claims description 23
- 108010010378 HLA-DP Antigens Proteins 0.000 claims description 22
- 102000015789 HLA-DP Antigens Human genes 0.000 claims description 22
- 108010062347 HLA-DQ Antigens Proteins 0.000 claims description 22
- 206010057249 Phagocytosis Diseases 0.000 claims description 22
- 230000008782 phagocytosis Effects 0.000 claims description 22
- 108700028369 Alleles Proteins 0.000 claims description 21
- 238000012217 deletion Methods 0.000 claims description 18
- 230000037430 deletion Effects 0.000 claims description 18
- 230000001965 increasing effect Effects 0.000 claims description 15
- 230000007423 decrease Effects 0.000 claims description 13
- 101100382122 Homo sapiens CIITA gene Proteins 0.000 claims description 12
- 102100026371 MHC class II transactivator Human genes 0.000 claims description 11
- 230000005867 T cell response Effects 0.000 claims description 10
- 230000005847 immunogenicity Effects 0.000 claims description 9
- 230000003247 decreasing effect Effects 0.000 claims description 8
- 210000001778 pluripotent stem cell Anatomy 0.000 claims description 8
- 101150000578 HLA-B gene Proteins 0.000 claims description 6
- 101150035071 HLA-C gene Proteins 0.000 claims description 6
- 230000036755 cellular response Effects 0.000 claims description 6
- 101150118346 HLA-A gene Proteins 0.000 claims description 4
- 210000001671 embryonic stem cell Anatomy 0.000 claims description 4
- 102000008096 B7-H1 Antigen Human genes 0.000 claims 7
- 238000002054 transplantation Methods 0.000 abstract description 11
- 238000002560 therapeutic procedure Methods 0.000 abstract description 4
- 238000004519 manufacturing process Methods 0.000 abstract description 2
- 210000001744 T-lymphocyte Anatomy 0.000 description 93
- 210000004509 vascular smooth muscle cell Anatomy 0.000 description 79
- 102100024216 Programmed cell death 1 ligand 1 Human genes 0.000 description 62
- 210000002889 endothelial cell Anatomy 0.000 description 62
- 102000040430 polynucleotide Human genes 0.000 description 53
- 108091033319 polynucleotide Proteins 0.000 description 53
- 239000002157 polynucleotide Substances 0.000 description 53
- 108091033409 CRISPR Proteins 0.000 description 39
- 102100034922 T-cell surface glycoprotein CD8 alpha chain Human genes 0.000 description 28
- 230000008685 targeting Effects 0.000 description 26
- 238000003556 assay Methods 0.000 description 25
- 238000010453 CRISPR/Cas method Methods 0.000 description 24
- 206010043276 Teratoma Diseases 0.000 description 24
- 230000006052 T cell proliferation Effects 0.000 description 21
- 238000010362 genome editing Methods 0.000 description 21
- 108090000765 processed proteins & peptides Proteins 0.000 description 21
- 108020004414 DNA Proteins 0.000 description 20
- 108020005004 Guide RNA Proteins 0.000 description 19
- 230000009467 reduction Effects 0.000 description 19
- 238000010354 CRISPR gene editing Methods 0.000 description 18
- 239000013612 plasmid Substances 0.000 description 16
- 102000004196 processed proteins & peptides Human genes 0.000 description 16
- 101000986085 Homo sapiens HLA class I histocompatibility antigen, alpha chain E Proteins 0.000 description 15
- 230000001404 mediated effect Effects 0.000 description 15
- 102000039446 nucleic acids Human genes 0.000 description 15
- 108020004707 nucleic acids Proteins 0.000 description 15
- 102100028970 HLA class I histocompatibility antigen, alpha chain E Human genes 0.000 description 14
- 229920001184 polypeptide Polymers 0.000 description 14
- 210000001266 CD8-positive T-lymphocyte Anatomy 0.000 description 13
- 239000002609 medium Substances 0.000 description 13
- 108091027544 Subgenomic mRNA Proteins 0.000 description 12
- 230000006044 T cell activation Effects 0.000 description 12
- 230000000735 allogeneic effect Effects 0.000 description 12
- 150000001413 amino acids Chemical class 0.000 description 12
- 238000003379 elimination reaction Methods 0.000 description 12
- 238000000338 in vitro Methods 0.000 description 12
- 102100040678 Programmed cell death protein 1 Human genes 0.000 description 11
- 101710089372 Programmed cell death protein 1 Proteins 0.000 description 11
- 238000003501 co-culture Methods 0.000 description 11
- 230000008030 elimination Effects 0.000 description 11
- 238000005516 engineering process Methods 0.000 description 11
- 238000001727 in vivo Methods 0.000 description 11
- 238000002347 injection Methods 0.000 description 11
- 239000007924 injection Substances 0.000 description 11
- 230000035772 mutation Effects 0.000 description 11
- 239000013641 positive control Substances 0.000 description 11
- 239000000047 product Substances 0.000 description 11
- 102000043129 MHC class I family Human genes 0.000 description 10
- 108091054437 MHC class I family Proteins 0.000 description 10
- 210000000612 antigen-presenting cell Anatomy 0.000 description 10
- 231100000135 cytotoxicity Toxicity 0.000 description 10
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 10
- 239000013642 negative control Substances 0.000 description 10
- 239000002773 nucleotide Substances 0.000 description 10
- 125000003729 nucleotide group Chemical group 0.000 description 10
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 10
- 238000010162 Tukey test Methods 0.000 description 9
- HFHDHCJBZVLPGP-RWMJIURBSA-N alpha-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO HFHDHCJBZVLPGP-RWMJIURBSA-N 0.000 description 9
- 230000004075 alteration Effects 0.000 description 9
- 230000003013 cytotoxicity Effects 0.000 description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 9
- 238000000684 flow cytometry Methods 0.000 description 9
- 238000011534 incubation Methods 0.000 description 9
- 238000003780 insertion Methods 0.000 description 9
- 230000037431 insertion Effects 0.000 description 9
- 238000001543 one-way ANOVA Methods 0.000 description 9
- 238000011529 RT qPCR Methods 0.000 description 8
- 238000001516 cell proliferation assay Methods 0.000 description 8
- 238000004520 electroporation Methods 0.000 description 8
- HKSZLNNOFSGOKW-UHFFFAOYSA-N ent-staurosporine Natural products C12=C3N4C5=CC=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1C1CC(NC)C(OC)C4(C)O1 HKSZLNNOFSGOKW-UHFFFAOYSA-N 0.000 description 8
- 230000002519 immonomodulatory effect Effects 0.000 description 8
- HKSZLNNOFSGOKW-FYTWVXJKSA-N staurosporine Chemical compound C12=C3N4C5=CC=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1[C@H]1C[C@@H](NC)[C@@H](OC)[C@]4(C)O1 HKSZLNNOFSGOKW-FYTWVXJKSA-N 0.000 description 8
- CGPUWJWCVCFERF-UHFFFAOYSA-N staurosporine Natural products C12=C3N4C5=CC=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1C1CC(NC)C(OC)C4(OC)O1 CGPUWJWCVCFERF-UHFFFAOYSA-N 0.000 description 8
- 238000006467 substitution reaction Methods 0.000 description 8
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 7
- 102100025137 Early activation antigen CD69 Human genes 0.000 description 7
- 101000934374 Homo sapiens Early activation antigen CD69 Proteins 0.000 description 7
- 230000004913 activation Effects 0.000 description 7
- 230000004888 barrier function Effects 0.000 description 7
- 230000002950 deficient Effects 0.000 description 7
- 239000012091 fetal bovine serum Substances 0.000 description 7
- 210000001654 germ layer Anatomy 0.000 description 7
- 108020004999 messenger RNA Proteins 0.000 description 7
- 238000007481 next generation sequencing Methods 0.000 description 7
- 230000002018 overexpression Effects 0.000 description 7
- 208000014451 palmoplantar keratoderma and congenital alopecia 2 Diseases 0.000 description 7
- 230000004044 response Effects 0.000 description 7
- 238000011144 upstream manufacturing Methods 0.000 description 7
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 6
- 108090000695 Cytokines Proteins 0.000 description 6
- 102000004127 Cytokines Human genes 0.000 description 6
- 238000013459 approach Methods 0.000 description 6
- 239000011324 bead Substances 0.000 description 6
- 238000003776 cleavage reaction Methods 0.000 description 6
- 230000000295 complement effect Effects 0.000 description 6
- 238000012790 confirmation Methods 0.000 description 6
- 208000035475 disorder Diseases 0.000 description 6
- 210000002304 esc Anatomy 0.000 description 6
- 210000001616 monocyte Anatomy 0.000 description 6
- 230000007017 scission Effects 0.000 description 6
- 102100031180 Hereditary hemochromatosis protein Human genes 0.000 description 5
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 description 5
- 108010002350 Interleukin-2 Proteins 0.000 description 5
- 102000003855 L-lactate dehydrogenase Human genes 0.000 description 5
- 108700023483 L-lactate dehydrogenases Proteins 0.000 description 5
- 108091054438 MHC class II family Proteins 0.000 description 5
- 241000699670 Mus sp. Species 0.000 description 5
- 229930182555 Penicillin Natural products 0.000 description 5
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 5
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 description 5
- 238000010459 TALEN Methods 0.000 description 5
- 108010043645 Transcription Activator-Like Effector Nucleases Proteins 0.000 description 5
- 230000000903 blocking effect Effects 0.000 description 5
- 239000000872 buffer Substances 0.000 description 5
- 230000022534 cell killing Effects 0.000 description 5
- 229960003722 doxycycline Drugs 0.000 description 5
- XQTWDDCIUJNLTR-CVHRZJFOSA-N doxycycline monohydrate Chemical compound O.O=C1C2=C(O)C=CC=C2[C@H](C)[C@@H]2C1=C(O)[C@]1(O)C(=O)C(C(N)=O)=C(O)[C@@H](N(C)C)[C@@H]1[C@H]2O XQTWDDCIUJNLTR-CVHRZJFOSA-N 0.000 description 5
- 230000012010 growth Effects 0.000 description 5
- 230000001771 impaired effect Effects 0.000 description 5
- 230000001939 inductive effect Effects 0.000 description 5
- 230000002401 inhibitory effect Effects 0.000 description 5
- 230000002147 killing effect Effects 0.000 description 5
- 230000004048 modification Effects 0.000 description 5
- 238000012986 modification Methods 0.000 description 5
- 229940049954 penicillin Drugs 0.000 description 5
- 230000037452 priming Effects 0.000 description 5
- 238000007480 sanger sequencing Methods 0.000 description 5
- 229960005322 streptomycin Drugs 0.000 description 5
- 238000010361 transduction Methods 0.000 description 5
- 230000026683 transduction Effects 0.000 description 5
- PHEDXBVPIONUQT-UHFFFAOYSA-N Cocarcinogen A1 Natural products CCCCCCCCCCCCCC(=O)OC1C(C)C2(O)C3C=C(C)C(=O)C3(O)CC(CO)=CC2C2C1(OC(C)=O)C2(C)C PHEDXBVPIONUQT-UHFFFAOYSA-N 0.000 description 4
- 102000053602 DNA Human genes 0.000 description 4
- 108010042407 Endonucleases Proteins 0.000 description 4
- 102000004533 Endonucleases Human genes 0.000 description 4
- 241000283074 Equus asinus Species 0.000 description 4
- 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 4
- 101000993059 Homo sapiens Hereditary hemochromatosis protein Proteins 0.000 description 4
- 101001057504 Homo sapiens Interferon-stimulated gene 20 kDa protein Proteins 0.000 description 4
- 101001055144 Homo sapiens Interleukin-2 receptor subunit alpha Proteins 0.000 description 4
- 101001023379 Homo sapiens Lysosome-associated membrane glycoprotein 1 Proteins 0.000 description 4
- 101000866971 Homo sapiens Putative HLA class I histocompatibility antigen, alpha chain H Proteins 0.000 description 4
- 102100026878 Interleukin-2 receptor subunit alpha Human genes 0.000 description 4
- 102100035133 Lysosome-associated membrane glycoprotein 1 Human genes 0.000 description 4
- 108700005092 MHC Class II Genes Proteins 0.000 description 4
- 102000043131 MHC class II family Human genes 0.000 description 4
- 108010029485 Protein Isoforms Proteins 0.000 description 4
- 102000001708 Protein Isoforms Human genes 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 230000009089 cytolysis Effects 0.000 description 4
- 230000034431 double-strand break repair via homologous recombination Effects 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 230000006870 function Effects 0.000 description 4
- 210000002865 immune cell Anatomy 0.000 description 4
- 210000000987 immune system Anatomy 0.000 description 4
- 238000002513 implantation Methods 0.000 description 4
- 239000003550 marker Substances 0.000 description 4
- PHEDXBVPIONUQT-RGYGYFBISA-N phorbol 13-acetate 12-myristate Chemical compound C([C@]1(O)C(=O)C(C)=C[C@H]1[C@@]1(O)[C@H](C)[C@H]2OC(=O)CCCCCCCCCCCCC)C(CO)=C[C@H]1[C@H]1[C@]2(OC(C)=O)C1(C)C PHEDXBVPIONUQT-RGYGYFBISA-N 0.000 description 4
- 230000002062 proliferating effect Effects 0.000 description 4
- 238000012216 screening Methods 0.000 description 4
- 230000000638 stimulation Effects 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 108091093088 Amplicon Proteins 0.000 description 3
- 108091026890 Coding region Proteins 0.000 description 3
- 108700005089 MHC Class I Genes Proteins 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- 102100026547 Platelet-derived growth factor receptor beta Human genes 0.000 description 3
- 108091008109 Pseudogenes Proteins 0.000 description 3
- 102000057361 Pseudogenes Human genes 0.000 description 3
- 239000012980 RPMI-1640 medium Substances 0.000 description 3
- 206010070834 Sensitisation Diseases 0.000 description 3
- 229940046176 T-cell checkpoint inhibitor Drugs 0.000 description 3
- 239000012644 T-cell checkpoint inhibitor Substances 0.000 description 3
- 206010052779 Transplant rejections Diseases 0.000 description 3
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 3
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 3
- 230000033289 adaptive immune response Effects 0.000 description 3
- 230000001464 adherent effect Effects 0.000 description 3
- 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 description 3
- 239000006143 cell culture medium Substances 0.000 description 3
- 230000001413 cellular effect Effects 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 239000012636 effector Substances 0.000 description 3
- 210000002242 embryoid body Anatomy 0.000 description 3
- 239000012634 fragment Substances 0.000 description 3
- 230000037433 frameshift Effects 0.000 description 3
- 238000011577 humanized mouse model Methods 0.000 description 3
- 229940124644 immune regulator Drugs 0.000 description 3
- 238000003018 immunoassay Methods 0.000 description 3
- 238000010166 immunofluorescence Methods 0.000 description 3
- 210000004263 induced pluripotent stem cell Anatomy 0.000 description 3
- 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 3
- 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 3
- 238000002955 isolation Methods 0.000 description 3
- 238000010859 live-cell imaging Methods 0.000 description 3
- 210000003716 mesoderm Anatomy 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 210000000680 phagosome Anatomy 0.000 description 3
- 230000035755 proliferation Effects 0.000 description 3
- 230000028327 secretion Effects 0.000 description 3
- 238000012163 sequencing technique Methods 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 238000010186 staining Methods 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 230000032258 transport Effects 0.000 description 3
- IGAZHQIYONOHQN-UHFFFAOYSA-N Alexa Fluor 555 Chemical compound C=12C=CC(=N)C(S(O)(=O)=O)=C2OC2=C(S(O)(=O)=O)C(N)=CC=C2C=1C1=CC=C(C(O)=O)C=C1C(O)=O IGAZHQIYONOHQN-UHFFFAOYSA-N 0.000 description 2
- 108091079001 CRISPR RNA Proteins 0.000 description 2
- 108010051109 Cell-Penetrating Peptides Proteins 0.000 description 2
- 102000020313 Cell-Penetrating Peptides Human genes 0.000 description 2
- 206010010099 Combined immunodeficiency Diseases 0.000 description 2
- 244000102216 Crateva tapia Species 0.000 description 2
- 235000003495 Crateva tapia Nutrition 0.000 description 2
- 230000004568 DNA-binding Effects 0.000 description 2
- 241000588724 Escherichia coli Species 0.000 description 2
- OHCQJHSOBUTRHG-KGGHGJDLSA-N FORSKOLIN Chemical compound O=C([C@@]12O)C[C@](C)(C=C)O[C@]1(C)[C@@H](OC(=O)C)[C@@H](O)[C@@H]1[C@]2(C)[C@@H](O)CCC1(C)C OHCQJHSOBUTRHG-KGGHGJDLSA-N 0.000 description 2
- 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- 101150074628 HLA-E gene Proteins 0.000 description 2
- 102000018713 Histocompatibility Antigens Class II Human genes 0.000 description 2
- 101000581981 Homo sapiens Neural cell adhesion molecule 1 Proteins 0.000 description 2
- 101000692455 Homo sapiens Platelet-derived growth factor receptor beta Proteins 0.000 description 2
- 101000863873 Homo sapiens Tyrosine-protein phosphatase non-receptor type substrate 1 Proteins 0.000 description 2
- 101150106931 IFNG gene Proteins 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- 108060004795 Methyltransferase Proteins 0.000 description 2
- 230000006051 NK cell activation Effects 0.000 description 2
- 102100027347 Neural cell adhesion molecule 1 Human genes 0.000 description 2
- 108010076504 Protein Sorting Signals Proteins 0.000 description 2
- 230000004570 RNA-binding Effects 0.000 description 2
- CVBNMWXECPZOLM-UHFFFAOYSA-N Rhamnetin Natural products COc1cc(O)c2C(=O)C(=C(Oc2c1)c3ccc(O)c(O)c3O)O CVBNMWXECPZOLM-UHFFFAOYSA-N 0.000 description 2
- 210000000662 T-lymphocyte subset Anatomy 0.000 description 2
- 108091028113 Trans-activating crRNA Proteins 0.000 description 2
- 108700019146 Transgenes Proteins 0.000 description 2
- 102100029948 Tyrosine-protein phosphatase non-receptor type substrate 1 Human genes 0.000 description 2
- 229940127174 UCHT1 Drugs 0.000 description 2
- 239000012190 activator Substances 0.000 description 2
- 101150063416 add gene Proteins 0.000 description 2
- 238000007792 addition Methods 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 230000027455 binding Effects 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 238000010804 cDNA synthesis Methods 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 230000024203 complement activation Effects 0.000 description 2
- 239000003636 conditioned culture medium Substances 0.000 description 2
- 238000003568 cytokine secretion assay Methods 0.000 description 2
- 231100000433 cytotoxic Toxicity 0.000 description 2
- 230000001472 cytotoxic effect Effects 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 238000006471 dimerization reaction Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 210000003981 ectoderm Anatomy 0.000 description 2
- 210000001900 endoderm Anatomy 0.000 description 2
- 239000003623 enhancer Substances 0.000 description 2
- 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 2
- 239000013604 expression vector Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 238000003209 gene knockout Methods 0.000 description 2
- 238000012239 gene modification Methods 0.000 description 2
- 102000054766 genetic haplotypes Human genes 0.000 description 2
- 230000005017 genetic modification Effects 0.000 description 2
- 235000013617 genetically modified food Nutrition 0.000 description 2
- 230000037451 immune surveillance Effects 0.000 description 2
- 230000001976 improved effect Effects 0.000 description 2
- 230000008595 infiltration Effects 0.000 description 2
- 238000001764 infiltration Methods 0.000 description 2
- 108091008042 inhibitory receptors Proteins 0.000 description 2
- 230000000977 initiatory effect Effects 0.000 description 2
- 230000010354 integration Effects 0.000 description 2
- 238000002843 lactate dehydrogenase assay Methods 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 201000006417 multiple sclerosis Diseases 0.000 description 2
- 230000009437 off-target effect Effects 0.000 description 2
- 230000000149 penetrating effect Effects 0.000 description 2
- -1 phosphorylated Chemical class 0.000 description 2
- 238000011176 pooling Methods 0.000 description 2
- 230000035935 pregnancy Effects 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 238000011002 quantification Methods 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 210000003289 regulatory T cell Anatomy 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 230000000717 retained effect Effects 0.000 description 2
- 230000008313 sensitization Effects 0.000 description 2
- 230000008477 smooth muscle tissue growth Effects 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 230000002269 spontaneous effect Effects 0.000 description 2
- 239000013589 supplement Substances 0.000 description 2
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 2
- 230000002103 transcriptional effect Effects 0.000 description 2
- 238000001890 transfection Methods 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- 230000001960 triggered effect Effects 0.000 description 2
- 210000003462 vein Anatomy 0.000 description 2
- 108700026220 vif Genes Proteins 0.000 description 2
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 1
- 102100040881 60S acidic ribosomal protein P0 Human genes 0.000 description 1
- HJCMDXDYPOUFDY-WHFBIAKZSA-N Ala-Gln Chemical compound C[C@H](N)C(=O)N[C@H](C(O)=O)CCC(N)=O HJCMDXDYPOUFDY-WHFBIAKZSA-N 0.000 description 1
- 241001439211 Almeida Species 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 108010081589 Becaplermin Proteins 0.000 description 1
- 102100027314 Beta-2-microglobulin Human genes 0.000 description 1
- 102100024505 Bone morphogenetic protein 4 Human genes 0.000 description 1
- 102100022002 CD59 glycoprotein Human genes 0.000 description 1
- 101710181688 CRISPR-associated endonuclease Cas9/Csn1 Proteins 0.000 description 1
- 101150069031 CSN2 gene Proteins 0.000 description 1
- AQGNHMOJWBZFQQ-UHFFFAOYSA-N CT 99021 Chemical compound CC1=CNC(C=2C(=NC(NCCNC=3N=CC(=CC=3)C#N)=NC=2)C=2C(=CC(Cl)=CC=2)Cl)=N1 AQGNHMOJWBZFQQ-UHFFFAOYSA-N 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 101710132601 Capsid protein Proteins 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
- 102100026550 Caspase-9 Human genes 0.000 description 1
- 108090000566 Caspase-9 Proteins 0.000 description 1
- 102100032643 Copine-5 Human genes 0.000 description 1
- 150000008574 D-amino acids Chemical class 0.000 description 1
- SUZLHDUTVMZSEV-UHFFFAOYSA-N Deoxycoleonol Natural products C12C(=O)CC(C)(C=C)OC2(C)C(OC(=O)C)C(O)C2C1(C)C(O)CCC2(C)C SUZLHDUTVMZSEV-UHFFFAOYSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 101710191360 Eosinophil cationic protein Proteins 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 102000016359 Fibronectins Human genes 0.000 description 1
- 108010067306 Fibronectins Proteins 0.000 description 1
- 108091092584 GDNA Proteins 0.000 description 1
- 101150106478 GPS1 gene Proteins 0.000 description 1
- 206010064571 Gene mutation Diseases 0.000 description 1
- 102000025850 HLA-A2 Antigen Human genes 0.000 description 1
- 108010074032 HLA-A2 Antigen Proteins 0.000 description 1
- 108700022944 Hemochromatosis Proteins 0.000 description 1
- 208000033981 Hereditary haemochromatosis Diseases 0.000 description 1
- 102000008949 Histocompatibility Antigens Class I Human genes 0.000 description 1
- 108010088652 Histocompatibility Antigens Class I Proteins 0.000 description 1
- 108010027412 Histocompatibility Antigens Class II Proteins 0.000 description 1
- 101000673456 Homo sapiens 60S acidic ribosomal protein P0 Proteins 0.000 description 1
- 101000762379 Homo sapiens Bone morphogenetic protein 4 Proteins 0.000 description 1
- 101000897400 Homo sapiens CD59 glycoprotein Proteins 0.000 description 1
- 101000941772 Homo sapiens Copine-5 Proteins 0.000 description 1
- 101100395310 Homo sapiens HLA-A gene Proteins 0.000 description 1
- 101000946889 Homo sapiens Monocyte differentiation antigen CD14 Proteins 0.000 description 1
- 101000979565 Homo sapiens Protein NLRC5 Proteins 0.000 description 1
- 229940076838 Immune checkpoint inhibitor Drugs 0.000 description 1
- 101150069255 KLRC1 gene Proteins 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- 229930182816 L-glutamine Natural products 0.000 description 1
- FFFHZYDWPBMWHY-VKHMYHEASA-N L-homocysteine Chemical compound OC(=O)[C@@H](N)CCS FFFHZYDWPBMWHY-VKHMYHEASA-N 0.000 description 1
- 241000713666 Lentivirus Species 0.000 description 1
- 101100404845 Macaca mulatta NKG2A gene Proteins 0.000 description 1
- 238000006957 Michael reaction Methods 0.000 description 1
- 229930192392 Mitomycin Natural products 0.000 description 1
- 102100035877 Monocyte differentiation antigen CD14 Human genes 0.000 description 1
- 101100219625 Mus musculus Casd1 gene Proteins 0.000 description 1
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 1
- 102100022682 NKG2-A/NKG2-B type II integral membrane protein Human genes 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 101100385413 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) csm-3 gene Proteins 0.000 description 1
- BZQFBWGGLXLEPQ-UHFFFAOYSA-N O-phosphoryl-L-serine Natural products OC(=O)C(N)COP(O)(O)=O BZQFBWGGLXLEPQ-UHFFFAOYSA-N 0.000 description 1
- 238000012408 PCR amplification Methods 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 108010051742 Platelet-Derived Growth Factor beta Receptor Proteins 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 101150044917 Prl3b1 gene Proteins 0.000 description 1
- 101150113550 Prl3d1 gene Proteins 0.000 description 1
- 102100023432 Protein NLRC5 Human genes 0.000 description 1
- 101710149951 Protein Tat Proteins 0.000 description 1
- 238000002123 RNA extraction Methods 0.000 description 1
- 101100047461 Rattus norvegicus Trpm8 gene Proteins 0.000 description 1
- 102100036007 Ribonuclease 3 Human genes 0.000 description 1
- 101710192197 Ribonuclease 3 Proteins 0.000 description 1
- 108010083644 Ribonucleases Proteins 0.000 description 1
- 102000006382 Ribonucleases Human genes 0.000 description 1
- 102000004389 Ribonucleoproteins Human genes 0.000 description 1
- 108010081734 Ribonucleoproteins Proteins 0.000 description 1
- 108010090804 Streptavidin Proteins 0.000 description 1
- 229940100389 Sulfonylurea Drugs 0.000 description 1
- 230000010782 T cell mediated cytotoxicity Effects 0.000 description 1
- 230000037453 T cell priming Effects 0.000 description 1
- 102000004399 TNF receptor-associated factor 3 Human genes 0.000 description 1
- 108090000922 TNF receptor-associated factor 3 Proteins 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 102000008790 VE-cadherin Human genes 0.000 description 1
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 1
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 238000002679 ablation Methods 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 108010023082 activin A Proteins 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000003044 adaptive effect Effects 0.000 description 1
- 230000004721 adaptive immunity Effects 0.000 description 1
- 238000004115 adherent culture Methods 0.000 description 1
- 125000000539 amino acid group Chemical class 0.000 description 1
- 230000001640 apoptogenic effect Effects 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 238000003149 assay kit Methods 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 108010081355 beta 2-Microglobulin Proteins 0.000 description 1
- 150000001576 beta-amino acids Chemical class 0.000 description 1
- 238000007622 bioinformatic analysis Methods 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 229930189065 blasticidin Natural products 0.000 description 1
- KQNZDYYTLMIZCT-KQPMLPITSA-N brefeldin A Chemical compound O[C@@H]1\C=C\C(=O)O[C@@H](C)CCC\C=C\[C@@H]2C[C@H](O)C[C@H]21 KQNZDYYTLMIZCT-KQPMLPITSA-N 0.000 description 1
- JUMGSHROWPPKFX-UHFFFAOYSA-N brefeldin-A Natural products CC1CCCC=CC2(C)CC(O)CC2(C)C(O)C=CC(=O)O1 JUMGSHROWPPKFX-UHFFFAOYSA-N 0.000 description 1
- 238000010805 cDNA synthesis kit Methods 0.000 description 1
- 108010018828 cadherin 5 Proteins 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 101150055766 cat gene Proteins 0.000 description 1
- 230000020411 cell activation Effects 0.000 description 1
- 230000006037 cell lysis Effects 0.000 description 1
- 230000002759 chromosomal effect Effects 0.000 description 1
- OHCQJHSOBUTRHG-UHFFFAOYSA-N colforsin Natural products OC12C(=O)CC(C)(C=C)OC1(C)C(OC(=O)C)C(O)C1C2(C)C(O)CCC1(C)C OHCQJHSOBUTRHG-UHFFFAOYSA-N 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 229910000366 copper(II) sulfate Inorganic materials 0.000 description 1
- JZCCFEFSEZPSOG-UHFFFAOYSA-L copper(II) sulfate pentahydrate Chemical compound O.O.O.O.O.[Cu+2].[O-]S([O-])(=O)=O JZCCFEFSEZPSOG-UHFFFAOYSA-L 0.000 description 1
- 101150037603 cst-1 gene Proteins 0.000 description 1
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 1
- 230000007402 cytotoxic response Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 229950006137 dexfosfoserine Drugs 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 230000005782 double-strand break Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000004043 dyeing Methods 0.000 description 1
- 230000005014 ectopic expression Effects 0.000 description 1
- 210000003162 effector t lymphocyte Anatomy 0.000 description 1
- 239000013613 expression plasmid Substances 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 210000003754 fetus Anatomy 0.000 description 1
- 238000002073 fluorescence micrograph Methods 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 231100000221 frame shift mutation induction Toxicity 0.000 description 1
- 239000012737 fresh medium Substances 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 210000004475 gamma-delta t lymphocyte Anatomy 0.000 description 1
- 238000003633 gene expression assay Methods 0.000 description 1
- 238000003205 genotyping method Methods 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 1
- 230000013632 homeostatic process Effects 0.000 description 1
- 238000009396 hybridization Methods 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 230000005934 immune activation Effects 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 230000006058 immune tolerance Effects 0.000 description 1
- 239000012274 immune-checkpoint protein inhibitor Substances 0.000 description 1
- 238000000126 in silico method Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000015788 innate immune response Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 230000000366 juvenile effect Effects 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 230000029226 lipidation Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 230000004777 loss-of-function mutation Effects 0.000 description 1
- 238000002826 magnetic-activated cell sorting Methods 0.000 description 1
- 230000000873 masking effect Effects 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 108091043314 miR-6891 stem-loop Proteins 0.000 description 1
- 229960004857 mitomycin Drugs 0.000 description 1
- 210000004980 monocyte derived macrophage Anatomy 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 210000004940 nucleus Anatomy 0.000 description 1
- 210000004287 null lymphocyte Anatomy 0.000 description 1
- VYNDHICBIRRPFP-UHFFFAOYSA-N pacific blue Chemical compound FC1=C(O)C(F)=C2OC(=O)C(C(=O)O)=CC2=C1 VYNDHICBIRRPFP-UHFFFAOYSA-N 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 230000000242 pagocytic effect Effects 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 230000006320 pegylation Effects 0.000 description 1
- 108010043655 penetratin Proteins 0.000 description 1
- MCYTYTUNNNZWOK-LCLOTLQISA-N penetratin Chemical compound C([C@H](NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CCCNC(N)=N)[C@@H](C)CC)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(N)=O)C1=CC=CC=C1 MCYTYTUNNNZWOK-LCLOTLQISA-N 0.000 description 1
- BZQFBWGGLXLEPQ-REOHCLBHSA-N phosphoserine Chemical compound OC(=O)[C@@H](N)COP(O)(O)=O BZQFBWGGLXLEPQ-REOHCLBHSA-N 0.000 description 1
- 108010011110 polyarginine Proteins 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 210000004986 primary T-cell Anatomy 0.000 description 1
- 210000004990 primary immune cell Anatomy 0.000 description 1
- 230000009993 protective function Effects 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 239000013074 reference sample Substances 0.000 description 1
- 230000001172 regenerating effect Effects 0.000 description 1
- 238000009877 rendering Methods 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000003757 reverse transcription PCR Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 239000012679 serum free medium Substances 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- YROXIXLRRCOBKF-UHFFFAOYSA-N sulfonylurea Chemical class OC(=N)N=S(=O)=O YROXIXLRRCOBKF-UHFFFAOYSA-N 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000012353 t test Methods 0.000 description 1
- 108091035539 telomere Proteins 0.000 description 1
- 102000055501 telomere Human genes 0.000 description 1
- 210000003411 telomere Anatomy 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 108091008023 transcriptional regulators Proteins 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 210000002993 trophoblast Anatomy 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 239000013598 vector Substances 0.000 description 1
- 239000013603 viral vector Substances 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 239000011534 wash buffer Substances 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
- C12N15/1138—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing against receptors or cell surface proteins
-
- 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
- C12N15/10—Processes for the isolation, preparation or purification of DNA or RNA
- C12N15/102—Mutagenizing nucleic acids
-
- 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]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K2035/122—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells for inducing tolerance or supression of immune responses
-
- 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
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/10—Type of nucleic acid
- C12N2310/20—Type of nucleic acid involving clustered regularly interspaced short palindromic repeats [CRISPRs]
-
- 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
- C12N2501/00—Active agents used in cell culture processes, e.g. differentation
- C12N2501/50—Cell markers; Cell surface determinants
- C12N2501/599—Cell markers; Cell surface determinants with CD designations not provided for elsewhere
-
- 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
- C12N2502/00—Coculture with; Conditioned medium produced by
- C12N2502/11—Coculture with; Conditioned medium produced by blood or immune system cells
- C12N2502/1114—T 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
- C12N2510/00—Genetically modified cells
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Genetics & Genomics (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Zoology (AREA)
- Biotechnology (AREA)
- Wood Science & Technology (AREA)
- General Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Developmental Biology & Embryology (AREA)
- Microbiology (AREA)
- Reproductive Health (AREA)
- Biochemistry (AREA)
- Gynecology & Obstetrics (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Physics & Mathematics (AREA)
- Plant Pathology (AREA)
- Cell Biology (AREA)
- Crystallography & Structural Chemistry (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201916277913A | 2019-02-15 | 2019-02-15 | |
| US16/277,913 | 2019-02-15 | ||
| US201916596697A | 2019-10-08 | 2019-10-08 | |
| US16/596,697 | 2019-10-08 | ||
| PCT/US2020/018467 WO2020168317A2 (fr) | 2019-02-15 | 2020-02-16 | Cellules souches donnatrices universelles et méthodes associées |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN113906048A true CN113906048A (zh) | 2022-01-07 |
Family
ID=72045137
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202080021860.7A Pending CN113906048A (zh) | 2019-02-15 | 2020-02-16 | 通用供体干细胞和相关方法 |
Country Status (11)
| Country | Link |
|---|---|
| EP (1) | EP3924375A4 (fr) |
| JP (1) | JP2022526218A (fr) |
| KR (1) | KR20210128440A (fr) |
| CN (1) | CN113906048A (fr) |
| AU (1) | AU2020223192A1 (fr) |
| BR (1) | BR112021016178A2 (fr) |
| CA (1) | CA3130398A1 (fr) |
| IL (1) | IL285619A (fr) |
| MX (1) | MX2021009842A (fr) |
| SG (1) | SG11202108891QA (fr) |
| WO (1) | WO2020168317A2 (fr) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP4149525A1 (fr) * | 2020-05-15 | 2023-03-22 | Rxcell Inc. | Cellules hypo-immunogènes et leurs utilisations dans des réponses immunitaires |
| CN114457021A (zh) * | 2020-10-30 | 2022-05-10 | 未来智人再生医学研究院(广州)有限公司 | 一种表达cd47抗体的多能干细胞及其衍生物与应用 |
| CN114525256A (zh) * | 2020-10-30 | 2022-05-24 | 未来智人再生医学研究院(广州)有限公司 | 一种表达Siglec-15阻断物的多能干细胞或其衍生物及应用 |
| US11459372B2 (en) | 2020-11-30 | 2022-10-04 | Crispr Therapeutics Ag | Gene-edited natural killer cells |
| AU2021396403A1 (en) * | 2020-12-11 | 2023-06-29 | Intellia Therapeutics, Inc. | Compositions and methods for reducing mhc class ii in a cell |
| WO2022140587A1 (fr) * | 2020-12-23 | 2022-06-30 | Intellia Therapeutics, Inc. | Compositions et procédés pour modifier génétiquement le ciita dans une cellule |
| CA3200509A1 (fr) | 2020-12-31 | 2022-07-07 | Sonja SCHREPFER | Methodes et compositions pour moduler une activite de car-t |
| AU2022283291A1 (en) | 2021-05-27 | 2023-11-02 | Sana Biotechnology, Inc. | Hypoimmunogenic cells comprising engineered hla-e or hla-g |
| CA3227613A1 (fr) | 2021-08-11 | 2023-02-16 | William Dowdle | Systemes inductibles pour modifier l'expression genique dans des cellules hypoimmunogenes |
| WO2023122337A1 (fr) | 2021-12-23 | 2023-06-29 | Sana Biotechnology, Inc. | Lymphocytes t à récepteur antigénique chimérique (car) pour le traitement d'une maladie auto-immune et méthodes associées |
| WO2023154578A1 (fr) | 2022-02-14 | 2023-08-17 | Sana Biotechnology, Inc. | Méthodes de traitement de patients présentant une thérapie préalable ayant échoué avec des cellules hypoimmunogènes |
| WO2023191063A1 (fr) * | 2022-04-01 | 2023-10-05 | 株式会社Logomix | Cellule appropriée pour l'ingénierie génique, l'ingénierie cellulaire et la médecine cellulaire, et son procédé de production |
| WO2024003349A1 (fr) | 2022-07-01 | 2024-01-04 | Novo Nordisk A/S | Amélioration de la différenciation neuronale de cellules progénitrices neurales du mésencéphale ventral |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107921148A (zh) * | 2015-05-08 | 2018-04-17 | 哈佛学院校长同事会 | 通用供体干细胞和相关方法 |
| WO2018132783A1 (fr) * | 2017-01-13 | 2018-07-19 | The Regents Of The University Of California | Cellules pluripotentes immunologiquement modifiées |
| CN108368520A (zh) * | 2015-11-04 | 2018-08-03 | 菲特治疗公司 | 多能细胞的基因组工程改造 |
-
2020
- 2020-02-16 JP JP2021547755A patent/JP2022526218A/ja active Pending
- 2020-02-16 WO PCT/US2020/018467 patent/WO2020168317A2/fr unknown
- 2020-02-16 EP EP20755906.3A patent/EP3924375A4/fr not_active Withdrawn
- 2020-02-16 AU AU2020223192A patent/AU2020223192A1/en not_active Abandoned
- 2020-02-16 BR BR112021016178A patent/BR112021016178A2/pt unknown
- 2020-02-16 SG SG11202108891QA patent/SG11202108891QA/en unknown
- 2020-02-16 CA CA3130398A patent/CA3130398A1/fr active Pending
- 2020-02-16 MX MX2021009842A patent/MX2021009842A/es unknown
- 2020-02-16 KR KR1020217029445A patent/KR20210128440A/ko unknown
- 2020-02-16 CN CN202080021860.7A patent/CN113906048A/zh active Pending
-
2021
- 2021-08-15 IL IL285619A patent/IL285619A/en unknown
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107921148A (zh) * | 2015-05-08 | 2018-04-17 | 哈佛学院校长同事会 | 通用供体干细胞和相关方法 |
| CN108368520A (zh) * | 2015-11-04 | 2018-08-03 | 菲特治疗公司 | 多能细胞的基因组工程改造 |
| WO2018132783A1 (fr) * | 2017-01-13 | 2018-07-19 | The Regents Of The University Of California | Cellules pluripotentes immunologiquement modifiées |
Also Published As
| Publication number | Publication date |
|---|---|
| IL285619A (en) | 2021-09-30 |
| KR20210128440A (ko) | 2021-10-26 |
| JP2022526218A (ja) | 2022-05-24 |
| SG11202108891QA (en) | 2021-09-29 |
| CA3130398A1 (fr) | 2020-08-20 |
| EP3924375A2 (fr) | 2021-12-22 |
| AU2020223192A1 (en) | 2021-09-09 |
| WO2020168317A8 (fr) | 2021-02-25 |
| WO2020168317A2 (fr) | 2020-08-20 |
| MX2021009842A (es) | 2021-12-10 |
| EP3924375A4 (fr) | 2023-03-22 |
| WO2020168317A3 (fr) | 2020-10-29 |
| BR112021016178A2 (pt) | 2021-11-03 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN113906048A (zh) | 通用供体干细胞和相关方法 | |
| Yamanaka | Pluripotent stem cell-based cell therapy—promise and challenges | |
| JP6985440B2 (ja) | クローディン６特異的免疫受容体およびｔ細胞エピトープ | |
| de Almeida et al. | Immunogenicity of pluripotent stem cells and their derivatives | |
| Dickinson et al. | Graft-versus-leukemia effect following hematopoietic stem cell transplantation for leukemia | |
| JP7123794B2 (ja) | 免疫細胞組成物及びそれを使用する方法 | |
| JP2022008381A (ja) | がんを治療するための方法 | |
| Riolobos et al. | HLA engineering of human pluripotent stem cells | |
| JP2020040969A (ja) | カスパーゼポリペプチドを使用して部分的なアポトーシスを誘導するための方法 | |
| JPWO2019160077A1 (ja) | 低抗原性細胞の製造方法 | |
| KR20180033537A (ko) | Pd-l1 발현 조혈 줄기 세포 및 용도 | |
| Zhao et al. | Strategies for genetically engineering hypoimmunogenic universal pluripotent stem cells | |
| JP2022526372A (ja) | ＨｖＧ疾患の処置における使用のためのＣＡＲ | |
| JP2007523640A (ja) | 免疫応答を誘導または調節する方法 | |
| Meissner et al. | Immune editing: overcoming immune barriers in stem cell transplantation | |
| AU2008247311A1 (en) | Novel thymic cellular populations and uses thereof | |
| US20210171903A1 (en) | Universal donor stem cells and related methods | |
| WO2016154176A1 (fr) | Méthodes et compositions pour modifier des cellules endothéliales | |
| Riddle et al. | Rescue of cytotoxic function in the CD8α knockout mouse by removal of MHC class II | |
| Anastasopoulou | Targeting mutant p53 in spontaneous cancer by T cell receptor gene therapy | |
| MacNabb | Dendritic Cells Prime Anti-tumor CD8 T Cell Responses through MHC-Dressing | |
| Nagy | Acceptance of allogeneic cell transplants without systemic immune suppression | |
| Wolf | Combining effects of one tumor-stroma recognizing TCR with one cancer‑cell specific TCR for eradication of solid tumors | |
| Garnica Caparrós | Transcriptional and epigenetic events underpinning the peptide-MHC-nanoparticle-induced transdifferentiation of T-follicular helper cells into T-regulatory type 1 cells in vivo | |
| Gaykema et al. | T-Cell Mediated Immune Rejection of Beta-2-Microglobulin Knockout Induced Pluripotent Stem Cell-Derived Kidney Organoids |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |