AU2022325231A1 - Genetically modified cells for allogeneic cell therapy to reduce complement-mediated inflammatory reactions - Google Patents

Info

Publication number

AU2022325231A1

AU2022325231A1 AU2022325231A AU2022325231A AU2022325231A1 AU 2022325231 A1 AU2022325231 A1 AU 2022325231A1 AU 2022325231 A AU2022325231 A AU 2022325231A AU 2022325231 A AU2022325231 A AU 2022325231A AU 2022325231 A1 AU2022325231 A1 AU 2022325231A1

Authority

AU

Australia

Prior art keywords

cell

engineered

cells

gene

engineered cell

Prior art date

2021-08-11

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

• Espacenet
• Global Dossier
• Discuss

• 230000001404 mediated effect Effects 0.000 title claims description 37
• 230000000295 complement effect Effects 0.000 title claims description 21
• 238000011129 allogeneic cell therapy Methods 0.000 title abstract description 4
• 206010061218 Inflammation Diseases 0.000 title 1
• 230000004054 inflammatory process Effects 0.000 title 1
• 230000014509 gene expression Effects 0.000 claims abstract description 332
• 230000004048 modification Effects 0.000 claims abstract description 170
• 238000012986 modification Methods 0.000 claims abstract description 170
• 102100022002 CD59 glycoprotein Human genes 0.000 claims abstract description 159
• 101000897400 Homo sapiens CD59 glycoprotein Proteins 0.000 claims abstract description 159
• 101000961414 Homo sapiens Membrane cofactor protein Proteins 0.000 claims abstract description 157
• 102100039373 Membrane cofactor protein Human genes 0.000 claims abstract description 155
• 230000001965 increasing effect Effects 0.000 claims abstract description 75
• 210000004027 cell Anatomy 0.000 claims description 775
• 238000000034 method Methods 0.000 claims description 344
• 102000040430 polynucleotide Human genes 0.000 claims description 247
• 108091033319 polynucleotide Proteins 0.000 claims description 247
• 239000002157 polynucleotide Substances 0.000 claims description 247
• 108090000623 proteins and genes Proteins 0.000 claims description 203
• 230000003614 tolerogenic effect Effects 0.000 claims description 178
• 101000868279 Homo sapiens Leukocyte surface antigen CD47 Proteins 0.000 claims description 134
• 102100032913 Leukocyte surface antigen CD47 Human genes 0.000 claims description 134
• 102100025680 Complement decay-accelerating factor Human genes 0.000 claims description 131
• 101000856022 Homo sapiens Complement decay-accelerating factor Proteins 0.000 claims description 130
• 210000004369 blood Anatomy 0.000 claims description 98
• 239000008280 blood Substances 0.000 claims description 98
• 102100035833 Histo-blood group ABO system transferase Human genes 0.000 claims description 84
• 101000802660 Homo sapiens Histo-blood group ABO system transferase Proteins 0.000 claims description 84
• 102100028970 HLA class I histocompatibility antigen, alpha chain E Human genes 0.000 claims description 78
• 101000986085 Homo sapiens HLA class I histocompatibility antigen, alpha chain E Proteins 0.000 claims description 78
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 76
• 201000010099 disease Diseases 0.000 claims description 66
• 102100024216 Programmed cell death 1 ligand 1 Human genes 0.000 claims description 63
• 230000002829 reductive effect Effects 0.000 claims description 61
• 239000003018 immunosuppressive agent Substances 0.000 claims description 59
• 229940125721 immunosuppressive agent Drugs 0.000 claims description 58
• 102000004169 proteins and genes Human genes 0.000 claims description 57
• 238000010362 genome editing Methods 0.000 claims description 52
• 239000000203 mixture Substances 0.000 claims description 50
• 102000043129 MHC class I family Human genes 0.000 claims description 49
• 108091054437 MHC class I family Proteins 0.000 claims description 49
• 239000013598 vector Substances 0.000 claims description 47
• 101001117317 Homo sapiens Programmed cell death 1 ligand 1 Proteins 0.000 claims description 45
• 108091054438 MHC class II family Proteins 0.000 claims description 43
• 102000043131 MHC class II family Human genes 0.000 claims description 43
• 101100382122 Homo sapiens CIITA gene Proteins 0.000 claims description 40
• 206010010144 Completed suicide Diseases 0.000 claims description 39
• 101150076800 B2M gene Proteins 0.000 claims description 38
• 101710163270 Nuclease Proteins 0.000 claims description 37
• 108010074708 B7-H1 Antigen Proteins 0.000 claims description 33
• 102100030886 Complement receptor type 1 Human genes 0.000 claims description 33
• 101000727061 Homo sapiens Complement receptor type 1 Proteins 0.000 claims description 33
• 108090000765 processed proteins & peptides Proteins 0.000 claims description 33
• 230000002779 inactivation Effects 0.000 claims description 31
• 102100028967 HLA class I histocompatibility antigen, alpha chain G Human genes 0.000 claims description 29
• -1 HLA-DM Proteins 0.000 claims description 29
• 108010024164 HLA-G Antigens Proteins 0.000 claims description 29
• 101000884271 Homo sapiens Signal transducer CD24 Proteins 0.000 claims description 29
• 102100038081 Signal transducer CD24 Human genes 0.000 claims description 29
• 239000000427 antigen Substances 0.000 claims description 29
• 108091007433 antigens Proteins 0.000 claims description 29
• 102000036639 antigens Human genes 0.000 claims description 29
• 230000000694 effects Effects 0.000 claims description 29
• 238000003780 insertion Methods 0.000 claims description 29
• 230000037431 insertion Effects 0.000 claims description 29
• 101001098352 Homo sapiens OX-2 membrane glycoprotein Proteins 0.000 claims description 27
• 102100037589 OX-2 membrane glycoprotein Human genes 0.000 claims description 27
• 210000002966 serum Anatomy 0.000 claims description 27
• 102100036846 C-C motif chemokine 21 Human genes 0.000 claims description 25
• 101000713085 Homo sapiens C-C motif chemokine 21 Proteins 0.000 claims description 25
• 102000004196 processed proteins & peptides Human genes 0.000 claims description 25
• 210000000130 stem cell Anatomy 0.000 claims description 25
• 102000004039 Caspase-9 Human genes 0.000 claims description 24
• 108090000566 Caspase-9 Proteins 0.000 claims description 24
• 108020004414 DNA Proteins 0.000 claims description 24
• 108700019146 Transgenes Proteins 0.000 claims description 24
• 230000001939 inductive effect Effects 0.000 claims description 24
• 229920001184 polypeptide Polymers 0.000 claims description 24
• 102100039648 Lactadherin Human genes 0.000 claims description 23
• 102100031988 Tumor necrosis factor ligand superfamily member 6 Human genes 0.000 claims description 23
• 108700028369 Alleles Proteins 0.000 claims description 22
• AVVWPBAENSWJCB-GASJEMHNSA-N D-mannofuranose Chemical compound OC[C@@H](O)[C@H]1OC(O)[C@@H](O)[C@H]1O AVVWPBAENSWJCB-GASJEMHNSA-N 0.000 claims description 22
• 101150089023 FASLG gene Proteins 0.000 claims description 22
• 101001034314 Homo sapiens Lactadherin Proteins 0.000 claims description 22
• 101000616876 Homo sapiens Mesencephalic astrocyte-derived neurotrophic factor Proteins 0.000 claims description 22
• 101000836075 Homo sapiens Serpin B9 Proteins 0.000 claims description 22
• 102100021833 Mesencephalic astrocyte-derived neurotrophic factor Human genes 0.000 claims description 22
• 102100025517 Serpin B9 Human genes 0.000 claims description 22
• 230000001413 cellular effect Effects 0.000 claims description 22
• 230000007812 deficiency Effects 0.000 claims description 22
• 108010017070 Zinc Finger Nucleases Proteins 0.000 claims description 21
• 210000001778 pluripotent stem cell Anatomy 0.000 claims description 21
• 108010080611 Cytosine Deaminase Proteins 0.000 claims description 20
• 102000000311 Cytosine Deaminase Human genes 0.000 claims description 20
• 230000002147 killing effect Effects 0.000 claims description 20
• 108091033409 CRISPR Proteins 0.000 claims description 19
• 108020005004 Guide RNA Proteins 0.000 claims description 19
• 108700002010 MHC class II transactivator Proteins 0.000 claims description 19
• 210000004153 islets of langerhan Anatomy 0.000 claims description 19
• 125000003275 alpha amino acid group Chemical group 0.000 claims description 16
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical group CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 15
• 150000001413 amino acids Chemical class 0.000 claims description 15
• 238000011282 treatment Methods 0.000 claims description 15
• 239000003795 chemical substances by application Substances 0.000 claims description 14
• 230000010354 integration Effects 0.000 claims description 14
• 102100028971 HLA class I histocompatibility antigen, C alpha chain Human genes 0.000 claims description 13
• 108010052199 HLA-C Antigens Proteins 0.000 claims description 13
• 238000010459 TALEN Methods 0.000 claims description 13
• 230000034431 double-strand break repair via homologous recombination Effects 0.000 claims description 13
• 210000005260 human cell Anatomy 0.000 claims description 13
• 210000004263 induced pluripotent stem cell Anatomy 0.000 claims description 13
• 230000002401 inhibitory effect Effects 0.000 claims description 13
• 241000701022 Cytomegalovirus Species 0.000 claims description 12
• 241000701044 Human gammaherpesvirus 4 Species 0.000 claims description 12
• 102000004389 Ribonucleoproteins Human genes 0.000 claims description 12
• 108010081734 Ribonucleoproteins Proteins 0.000 claims description 12
• 241000714474 Rous sarcoma virus Species 0.000 claims description 12
• 230000030833 cell death Effects 0.000 claims description 12
• ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 claims description 12
• 229960002930 sirolimus Drugs 0.000 claims description 12
• QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 claims description 12
• 102000003814 Interleukin-10 Human genes 0.000 claims description 11
• 108090000174 Interleukin-10 Proteins 0.000 claims description 11
• 230000004075 alteration Effects 0.000 claims description 11
• 210000002889 endothelial cell Anatomy 0.000 claims description 11
• 239000003112 inhibitor Substances 0.000 claims description 11
• 230000008685 targeting Effects 0.000 claims description 11
• 102100027207 CD27 antigen Human genes 0.000 claims description 10
• 108010076667 Caspases Proteins 0.000 claims description 10
• 102000011727 Caspases Human genes 0.000 claims description 10
• 101000914511 Homo sapiens CD27 antigen Proteins 0.000 claims description 10
• 101001037256 Homo sapiens Indoleamine 2,3-dioxygenase 1 Proteins 0.000 claims description 10
• 101000917858 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-A Proteins 0.000 claims description 10
• 101000917839 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-B Proteins 0.000 claims description 10
• 101001000998 Homo sapiens Protein phosphatase 1 regulatory subunit 12C Proteins 0.000 claims description 10
• 102100040061 Indoleamine 2,3-dioxygenase 1 Human genes 0.000 claims description 10
• 102100035620 Protein phosphatase 1 regulatory subunit 12C Human genes 0.000 claims description 10
• 210000001744 T-lymphocyte Anatomy 0.000 claims description 10
• 102000006601 Thymidine Kinase Human genes 0.000 claims description 10
• 108020004440 Thymidine kinase Proteins 0.000 claims description 10
• 230000004913 activation Effects 0.000 claims description 10
• 238000002659 cell therapy Methods 0.000 claims description 10
• 238000012217 deletion Methods 0.000 claims description 10
• 230000037430 deletion Effects 0.000 claims description 10
• 208000035475 disorder Diseases 0.000 claims description 10
• 230000006870 function Effects 0.000 claims description 10
• 102000001301 EGF receptor Human genes 0.000 claims description 9
• 206010012601 diabetes mellitus Diseases 0.000 claims description 9
• 239000003814 drug Substances 0.000 claims description 9
• 231100000221 frame shift mutation induction Toxicity 0.000 claims description 9
• 230000037433 frameshift Effects 0.000 claims description 9
• 241001529453 unidentified herpesvirus Species 0.000 claims description 9
• 206010028980 Neoplasm Diseases 0.000 claims description 8
• 101710153660 Nuclear receptor corepressor 2 Proteins 0.000 claims description 8
• 108010073062 Transcription Activator-Like Effectors Proteins 0.000 claims description 8
• 108010047933 Tumor Necrosis Factor alpha-Induced Protein 3 Proteins 0.000 claims description 8
• 102100024596 Tumor necrosis factor alpha-induced protein 3 Human genes 0.000 claims description 8
• 230000006907 apoptotic process Effects 0.000 claims description 8
• 229960000106 biosimilars Drugs 0.000 claims description 8
• 201000011510 cancer Diseases 0.000 claims description 8
• 208000019423 liver disease Diseases 0.000 claims description 8
• 210000000822 natural killer cell Anatomy 0.000 claims description 8
• 229940002612 prodrug Drugs 0.000 claims description 8
• 239000000651 prodrug Substances 0.000 claims description 8
• 241000283690 Bos taurus Species 0.000 claims description 7
• 210000001671 embryonic stem cell Anatomy 0.000 claims description 7
• 210000003494 hepatocyte Anatomy 0.000 claims description 7
• 210000002865 immune cell Anatomy 0.000 claims description 7
• 210000001685 thyroid gland Anatomy 0.000 claims description 7
• 108010088751 Albumins Proteins 0.000 claims description 6
• 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 claims description 6
• 102100024217 CAMPATH-1 antigen Human genes 0.000 claims description 6
• 101150017501 CCR5 gene Proteins 0.000 claims description 6
• 108010065524 CD52 Antigen Proteins 0.000 claims description 6
• 101150066398 CXCR4 gene Proteins 0.000 claims description 6
• 108010019670 Chimeric Antigen Receptors Proteins 0.000 claims description 6
• 101150055030 Clybl gene Proteins 0.000 claims description 6
• 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 claims description 6
• 101100321817 Human parvovirus B19 (strain HV) 7.5K gene Proteins 0.000 claims description 6
• 102100029185 Low affinity immunoglobulin gamma Fc region receptor III-B Human genes 0.000 claims description 6
• 241000829100 Macaca mulatta polyomavirus 1 Species 0.000 claims description 6
• 241000713333 Mouse mammary tumor virus Species 0.000 claims description 6
• 102000008579 Transposases Human genes 0.000 claims description 6
• 108010020764 Transposases Proteins 0.000 claims description 6
• 241000700618 Vaccinia virus Species 0.000 claims description 6
• 241000700605 Viruses Species 0.000 claims description 6
• 210000004102 animal cell Anatomy 0.000 claims description 6
• 150000001875 compounds Chemical class 0.000 claims description 6
• 208000021921 corneal disease Diseases 0.000 claims description 6
• 239000002577 cryoprotective agent Substances 0.000 claims description 6
• 208000024891 symptom Diseases 0.000 claims description 6
• 238000002054 transplantation Methods 0.000 claims description 6
• 241000701161 unidentified adenovirus Species 0.000 claims description 6
• 101100067974 Arabidopsis thaliana POP2 gene Proteins 0.000 claims description 5
• 101710149863 C-C chemokine receptor type 4 Proteins 0.000 claims description 5
• 102100032976 CCR4-NOT transcription complex subunit 6 Human genes 0.000 claims description 5
• 102100021158 Double homeobox protein 4 Human genes 0.000 claims description 5
• 208000030836 Hashimoto thyroiditis Diseases 0.000 claims description 5
• 101000968549 Homo sapiens Double homeobox protein 4 Proteins 0.000 claims description 5
• 101100118549 Homo sapiens EGFR gene Proteins 0.000 claims description 5
• 101000851376 Homo sapiens Tumor necrosis factor receptor superfamily member 8 Proteins 0.000 claims description 5
• 101100123851 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) HER1 gene Proteins 0.000 claims description 5
• 102100036857 Tumor necrosis factor receptor superfamily member 8 Human genes 0.000 claims description 5
• 210000003719 b-lymphocyte Anatomy 0.000 claims description 5
• 210000000601 blood cell Anatomy 0.000 claims description 5
• 229940079593 drug Drugs 0.000 claims description 5
• 230000003511 endothelial effect Effects 0.000 claims description 5
• 210000000981 epithelium Anatomy 0.000 claims description 5
• 238000002347 injection Methods 0.000 claims description 5
• 239000007924 injection Substances 0.000 claims description 5
• 210000003061 neural cell Anatomy 0.000 claims description 5
• 230000002207 retinal effect Effects 0.000 claims description 5
• 210000004927 skin cell Anatomy 0.000 claims description 5
• 150000003384 small molecules Chemical class 0.000 claims description 5
• 102100023990 60S ribosomal protein L17 Human genes 0.000 claims description 4
• 208000025324 B-cell acute lymphoblastic leukemia Diseases 0.000 claims description 4
• 102100027544 Blood group Rh(D) polypeptide Human genes 0.000 claims description 4
• CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 claims description 4
• PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 claims description 4
• 108010036949 Cyclosporine Proteins 0.000 claims description 4
• 102000006395 Globulins Human genes 0.000 claims description 4
• 108010044091 Globulins Proteins 0.000 claims description 4
• 102100041003 Glutamate carboxypeptidase 2 Human genes 0.000 claims description 4
• 101000580024 Homo sapiens Blood group Rh(D) polypeptide Proteins 0.000 claims description 4
• 101000892862 Homo sapiens Glutamate carboxypeptidase 2 Proteins 0.000 claims description 4
• 101001133056 Homo sapiens Mucin-1 Proteins 0.000 claims description 4
• 101000979565 Homo sapiens Protein NLRC5 Proteins 0.000 claims description 4
• 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 claims description 4
• 101000635804 Homo sapiens Tissue factor Proteins 0.000 claims description 4
• 101150105660 MFGE8 gene Proteins 0.000 claims description 4
• 102100034256 Mucin-1 Human genes 0.000 claims description 4
• 101001024425 Mus musculus Ig gamma-2A chain C region secreted form Proteins 0.000 claims description 4
• 206010035226 Plasma cell myeloma Diseases 0.000 claims description 4
• 101710089372 Programmed cell death protein 1 Proteins 0.000 claims description 4
• 102100023432 Protein NLRC5 Human genes 0.000 claims description 4
• 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 claims description 4
• QJJXYPPXXYFBGM-LFZNUXCKSA-N Tacrolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1\C=C(/C)[C@@H]1[C@H](C)[C@@H](O)CC(=O)[C@H](CC=C)/C=C(C)/C[C@H](C)C[C@H](OC)[C@H]([C@H](C[C@H]2C)OC)O[C@@]2(O)C(=O)C(=O)N2CCCC[C@H]2C(=O)O1 QJJXYPPXXYFBGM-LFZNUXCKSA-N 0.000 claims description 4
• 230000001494 anti-thymocyte effect Effects 0.000 claims description 4
• 230000027455 binding Effects 0.000 claims description 4
• 229960001265 ciclosporin Drugs 0.000 claims description 4
• 239000003246 corticosteroid Substances 0.000 claims description 4
• 229960004397 cyclophosphamide Drugs 0.000 claims description 4
• 229930182912 cyclosporin Natural products 0.000 claims description 4
• 230000003013 cytotoxicity Effects 0.000 claims description 4
• 231100000135 cytotoxicity Toxicity 0.000 claims description 4
• 239000003623 enhancer Substances 0.000 claims description 4
• 239000012595 freezing medium Substances 0.000 claims description 4
• 230000002518 glial effect Effects 0.000 claims description 4
• 210000002064 heart cell Anatomy 0.000 claims description 4
• 230000002519 immonomodulatory effect Effects 0.000 claims description 4
• 230000028993 immune response Effects 0.000 claims description 4
• 230000002757 inflammatory effect Effects 0.000 claims description 4
• 238000010255 intramuscular injection Methods 0.000 claims description 4
• 239000007927 intramuscular injection Substances 0.000 claims description 4
• 208000017169 kidney disease Diseases 0.000 claims description 4
• 239000003446 ligand Substances 0.000 claims description 4
• GLVAUDGFNGKCSF-UHFFFAOYSA-N mercaptopurine Chemical compound S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 claims description 4
• 238000012544 monitoring process Methods 0.000 claims description 4
• RTGDFNSFWBGLEC-SYZQJQIISA-N mycophenolate mofetil Chemical compound COC1=C(C)C=2COC(=O)C=2C(O)=C1C\C=C(/C)CCC(=O)OCCN1CCOCC1 RTGDFNSFWBGLEC-SYZQJQIISA-N 0.000 claims description 4
• 229960004866 mycophenolate mofetil Drugs 0.000 claims description 4
• 229940124597 therapeutic agent Drugs 0.000 claims description 4
• 230000002792 vascular Effects 0.000 claims description 4
• 101710169336 5'-deoxyadenosine deaminase Proteins 0.000 claims description 3
• 102000055025 Adenosine deaminases Human genes 0.000 claims description 3
• 102100020986 DNA-binding protein RFX5 Human genes 0.000 claims description 3
• 102100021044 DNA-binding protein RFXANK Human genes 0.000 claims description 3
• 102100028972 HLA class I histocompatibility antigen, A alpha chain Human genes 0.000 claims description 3
• 102100028976 HLA class I histocompatibility antigen, B alpha chain Human genes 0.000 claims description 3
• 102100031547 HLA class II histocompatibility antigen, DO alpha chain Human genes 0.000 claims description 3
• 102100031546 HLA class II histocompatibility antigen, DO beta chain Human genes 0.000 claims description 3
• 108010075704 HLA-A Antigens Proteins 0.000 claims description 3
• 108010058607 HLA-B Antigens Proteins 0.000 claims description 3
• 108010010378 HLA-DP Antigens Proteins 0.000 claims description 3
• 102000015789 HLA-DP Antigens Human genes 0.000 claims description 3
• 108010062347 HLA-DQ Antigens Proteins 0.000 claims description 3
• 108010058597 HLA-DR Antigens Proteins 0.000 claims description 3
• 102000006354 HLA-DR Antigens Human genes 0.000 claims description 3
• 101001075432 Homo sapiens DNA-binding protein RFX5 Proteins 0.000 claims description 3
• 101001075464 Homo sapiens DNA-binding protein RFXANK Proteins 0.000 claims description 3
• 101000866278 Homo sapiens HLA class II histocompatibility antigen, DO alpha chain Proteins 0.000 claims description 3
• 101000866281 Homo sapiens HLA class II histocompatibility antigen, DO beta chain Proteins 0.000 claims description 3
• 101000991061 Homo sapiens MHC class I polypeptide-related sequence B Proteins 0.000 claims description 3
• 101001075466 Homo sapiens Regulatory factor X-associated protein Proteins 0.000 claims description 3
• 102100030301 MHC class I polypeptide-related sequence A Human genes 0.000 claims description 3
• 102100030300 MHC class I polypeptide-related sequence B Human genes 0.000 claims description 3
• 241001494479 Pecora Species 0.000 claims description 3
• 102100021043 Regulatory factor X-associated protein Human genes 0.000 claims description 3
• 230000001154 acute effect Effects 0.000 claims description 3
• 229960005395 cetuximab Drugs 0.000 claims description 3
• 230000024203 complement activation Effects 0.000 claims description 3
• 230000001506 immunosuppresive effect Effects 0.000 claims description 3
• 208000003747 lymphoid leukemia Diseases 0.000 claims description 3
• 210000002540 macrophage Anatomy 0.000 claims description 3
• 229950007699 mogamulizumab Drugs 0.000 claims description 3
• 229960003347 obinutuzumab Drugs 0.000 claims description 3
• 229950009090 ocaratuzumab Drugs 0.000 claims description 3
• 239000008194 pharmaceutical composition Substances 0.000 claims description 3
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
• 229960004641 rituximab Drugs 0.000 claims description 3
• 229940060960 tomuzotuximab Drugs 0.000 claims description 3
• 229950004593 ublituximab Drugs 0.000 claims description 3
• 102100031585 ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Human genes 0.000 claims description 2
• 206010052747 Adenocarcinoma pancreas Diseases 0.000 claims description 2
• 206010005003 Bladder cancer Diseases 0.000 claims description 2
• 206010006187 Breast cancer Diseases 0.000 claims description 2
• 208000026310 Breast neoplasm Diseases 0.000 claims description 2
• 101150013553 CD40 gene Proteins 0.000 claims description 2
• 206010009944 Colon cancer Diseases 0.000 claims description 2
• 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 2
• 206010010356 Congenital anomaly Diseases 0.000 claims description 2
• 108010039471 Fas Ligand Protein Proteins 0.000 claims description 2
• 206010016654 Fibrosis Diseases 0.000 claims description 2
• 201000001925 Fuchs' endothelial dystrophy Diseases 0.000 claims description 2
• 102100026122 High affinity immunoglobulin gamma Fc receptor I Human genes 0.000 claims description 2
• 101000777636 Homo sapiens ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Proteins 0.000 claims description 2
• 101100066427 Homo sapiens FCGR1A gene Proteins 0.000 claims description 2
• 101000599951 Homo sapiens Insulin-like growth factor I Proteins 0.000 claims description 2
• 101001063392 Homo sapiens Lymphocyte function-associated antigen 3 Proteins 0.000 claims description 2
• 101000763322 Homo sapiens M1-specific T cell receptor beta chain Proteins 0.000 claims description 2
• 101000996109 Homo sapiens Neuroligin-4, Y-linked Proteins 0.000 claims description 2
• 101000613375 Homo sapiens Protocadherin-11 Y-linked Proteins 0.000 claims description 2
• 101000738771 Homo sapiens Receptor-type tyrosine-protein phosphatase C Proteins 0.000 claims description 2
• 101000763321 Homo sapiens T cell receptor beta chain MC.7.G5 Proteins 0.000 claims description 2
• 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 claims description 2
• 102100037850 Interferon gamma Human genes 0.000 claims description 2
• 108010074328 Interferon-gamma Proteins 0.000 claims description 2
• 108010038453 Interleukin-2 Receptors Proteins 0.000 claims description 2
• 102000010789 Interleukin-2 Receptors Human genes 0.000 claims description 2
• 108090000978 Interleukin-4 Proteins 0.000 claims description 2
• 102000004388 Interleukin-4 Human genes 0.000 claims description 2
• 108010002616 Interleukin-5 Proteins 0.000 claims description 2
• 102000000743 Interleukin-5 Human genes 0.000 claims description 2
• 108090001005 Interleukin-6 Proteins 0.000 claims description 2
• 108010002586 Interleukin-7 Proteins 0.000 claims description 2
• 108090001007 Interleukin-8 Proteins 0.000 claims description 2
• UETNIIAIRMUTSM-UHFFFAOYSA-N Jacareubin Natural products CC1(C)OC2=CC3Oc4c(O)c(O)ccc4C(=O)C3C(=C2C=C1)O UETNIIAIRMUTSM-UHFFFAOYSA-N 0.000 claims description 2
• FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 claims description 2
• 208000031671 Large B-Cell Diffuse Lymphoma Diseases 0.000 claims description 2
• 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 2
• 102100030984 Lymphocyte function-associated antigen 3 Human genes 0.000 claims description 2
• 208000028018 Lymphocytic leukaemia Diseases 0.000 claims description 2
• 102100026964 M1-specific T cell receptor beta chain Human genes 0.000 claims description 2
• HZQDCMWJEBCWBR-UUOKFMHZSA-N Mizoribine Chemical compound OC1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 HZQDCMWJEBCWBR-UUOKFMHZSA-N 0.000 claims description 2
• 208000034578 Multiple myelomas Diseases 0.000 claims description 2
• 101001055320 Myxine glutinosa Insulin-like growth factor Proteins 0.000 claims description 2
• 206010029260 Neuroblastoma Diseases 0.000 claims description 2
• 102100034448 Neuroligin-4, Y-linked Human genes 0.000 claims description 2
• 208000022873 Ocular disease Diseases 0.000 claims description 2
• 206010033128 Ovarian cancer Diseases 0.000 claims description 2
• 206010061535 Ovarian neoplasm Diseases 0.000 claims description 2
• 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 2
• 102100040932 Protocadherin-11 Y-linked Human genes 0.000 claims description 2
• 102100037422 Receptor-type tyrosine-protein phosphatase C Human genes 0.000 claims description 2
• 208000005718 Stomach Neoplasms Diseases 0.000 claims description 2
• 102100029452 T cell receptor alpha chain constant Human genes 0.000 claims description 2
• 102100025237 T-cell surface antigen CD2 Human genes 0.000 claims description 2
• 102100036011 T-cell surface glycoprotein CD4 Human genes 0.000 claims description 2
• 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 claims description 2
• 102400000160 Thymopentin Human genes 0.000 claims description 2
• 101800001703 Thymopentin Proteins 0.000 claims description 2
• 208000024799 Thyroid disease Diseases 0.000 claims description 2
• 102100030859 Tissue factor Human genes 0.000 claims description 2
• 102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 claims description 2
• 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 2
• 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 2
• 239000003430 antimalarial agent Substances 0.000 claims description 2
• 229940033495 antimalarials Drugs 0.000 claims description 2
• LMEKQMALGUDUQG-UHFFFAOYSA-N azathioprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC=NC2=C1NC=N2 LMEKQMALGUDUQG-UHFFFAOYSA-N 0.000 claims description 2
• 229960002170 azathioprine Drugs 0.000 claims description 2
• PHEZJEYUWHETKO-UHFFFAOYSA-N brequinar Chemical compound N1=C2C=CC(F)=CC2=C(C(O)=O)C(C)=C1C(C=C1)=CC=C1C1=CC=CC=C1F PHEZJEYUWHETKO-UHFFFAOYSA-N 0.000 claims description 2
• 229950010231 brequinar Drugs 0.000 claims description 2
• 230000006037 cell lysis Effects 0.000 claims description 2
• 230000007882 cirrhosis Effects 0.000 claims description 2
• 208000019425 cirrhosis of liver Diseases 0.000 claims description 2
• 210000000399 corneal endothelial cell Anatomy 0.000 claims description 2
• 229960001334 corticosteroids Drugs 0.000 claims description 2
• 206010012818 diffuse large B-cell lymphoma Diseases 0.000 claims description 2
• 210000002919 epithelial cell Anatomy 0.000 claims description 2
• 201000006585 gastric adenocarcinoma Diseases 0.000 claims description 2
• 206010017758 gastric cancer Diseases 0.000 claims description 2
• 208000005017 glioblastoma Diseases 0.000 claims description 2
• 150000002343 gold Chemical class 0.000 claims description 2
• 230000002440 hepatic effect Effects 0.000 claims description 2
• 206010073071 hepatocellular carcinoma Diseases 0.000 claims description 2
• 231100000844 hepatocellular carcinoma Toxicity 0.000 claims description 2
• 230000002163 immunogen Effects 0.000 claims description 2
• 230000028709 inflammatory response Effects 0.000 claims description 2
• 238000010253 intravenous injection Methods 0.000 claims description 2
• 229960000681 leflunomide Drugs 0.000 claims description 2
• VHOGYURTWQBHIL-UHFFFAOYSA-N leflunomide Chemical compound O1N=CC(C(=O)NC=2C=CC(=CC=2)C(F)(F)F)=C1C VHOGYURTWQBHIL-UHFFFAOYSA-N 0.000 claims description 2
• 210000004185 liver Anatomy 0.000 claims description 2
• 201000007270 liver cancer Diseases 0.000 claims description 2
• 208000014018 liver neoplasm Diseases 0.000 claims description 2
• 201000005202 lung cancer Diseases 0.000 claims description 2
• 208000020816 lung neoplasm Diseases 0.000 claims description 2
• 201000005243 lung squamous cell carcinoma Diseases 0.000 claims description 2
• 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 2
• 210000001939 mature NK cell Anatomy 0.000 claims description 2
• 229960001428 mercaptopurine Drugs 0.000 claims description 2
• 229960000485 methotrexate Drugs 0.000 claims description 2
• HPNSFSBZBAHARI-UHFFFAOYSA-N micophenolic acid Natural products OC1=C(CC=C(C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-UHFFFAOYSA-N 0.000 claims description 2
• 229950000844 mizoribine Drugs 0.000 claims description 2
• 229960000951 mycophenolic acid Drugs 0.000 claims description 2
• HPNSFSBZBAHARI-RUDMXATFSA-N mycophenolic acid Chemical compound OC1=C(C\C=C(/C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-RUDMXATFSA-N 0.000 claims description 2
• 230000031942 natural killer cell mediated cytotoxicity Effects 0.000 claims description 2
• 210000004498 neuroglial cell Anatomy 0.000 claims description 2
• 208000002154 non-small cell lung carcinoma Diseases 0.000 claims description 2
• 201000002094 pancreatic adenocarcinoma Diseases 0.000 claims description 2
• 201000002528 pancreatic cancer Diseases 0.000 claims description 2
• 208000008443 pancreatic carcinoma Diseases 0.000 claims description 2
• 239000002243 precursor Substances 0.000 claims description 2
• XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 claims description 2
• 229960004618 prednisone Drugs 0.000 claims description 2
• 230000000069 prophylactic effect Effects 0.000 claims description 2
• 102000005962 receptors Human genes 0.000 claims description 2
• 108020003175 receptors Proteins 0.000 claims description 2
• 208000017520 skin disease Diseases 0.000 claims description 2
• 201000011549 stomach cancer Diseases 0.000 claims description 2
• NCEXYHBECQHGNR-QZQOTICOSA-N sulfasalazine Chemical compound C1=C(O)C(C(=O)O)=CC(\N=N\C=2C=CC(=CC=2)S(=O)(=O)NC=2N=CC=CC=2)=C1 NCEXYHBECQHGNR-QZQOTICOSA-N 0.000 claims description 2
• 229960001940 sulfasalazine Drugs 0.000 claims description 2
• NCEXYHBECQHGNR-UHFFFAOYSA-N sulfasalazine Natural products C1=C(O)C(C(=O)O)=CC(N=NC=2C=CC(=CC=2)S(=O)(=O)NC=2N=CC=CC=2)=C1 NCEXYHBECQHGNR-UHFFFAOYSA-N 0.000 claims description 2
• 230000001629 suppression Effects 0.000 claims description 2
• 230000008718 systemic inflammatory response Effects 0.000 claims description 2
• 230000001225 therapeutic effect Effects 0.000 claims description 2
• PSWFFKRAVBDQEG-YGQNSOCVSA-N thymopentin Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 PSWFFKRAVBDQEG-YGQNSOCVSA-N 0.000 claims description 2
• 229960004517 thymopentin Drugs 0.000 claims description 2
• 208000021510 thyroid gland disease Diseases 0.000 claims description 2
• 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims description 2
• 201000005112 urinary bladder cancer Diseases 0.000 claims description 2
• 102100027314 Beta-2-microglobulin Human genes 0.000 claims 10
• 102100026371 MHC class II transactivator Human genes 0.000 claims 10
• 210000003958 hematopoietic stem cell Anatomy 0.000 claims 7
• 108020003285 Isocitrate lyase Proteins 0.000 claims 6
• 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims 6
• 208000018706 hematopoietic system disease Diseases 0.000 claims 6
• 210000002901 mesenchymal stem cell Anatomy 0.000 claims 5
• 201000004311 Gilles de la Tourette syndrome Diseases 0.000 claims 4
• 101150021904 HMGB1 gene Proteins 0.000 claims 4
• 206010059176 Juvenile idiopathic arthritis Diseases 0.000 claims 4
• 101150091651 MICB gene Proteins 0.000 claims 4
• 208000000323 Tourette Syndrome Diseases 0.000 claims 4
• 208000016620 Tourette disease Diseases 0.000 claims 4
• 208000032839 leukemia Diseases 0.000 claims 4
• 208000023275 Autoimmune disease Diseases 0.000 claims 3
• 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 claims 3
• 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 claims 3
• 238000010354 CRISPR gene editing Methods 0.000 claims 3
• 208000010833 Chronic myeloid leukaemia Diseases 0.000 claims 3
• 102100029722 Ectonucleoside triphosphate diphosphohydrolase 1 Human genes 0.000 claims 3
• 208000007465 Giant cell arteritis Diseases 0.000 claims 3
• 101001012447 Homo sapiens Ectonucleoside triphosphate diphosphohydrolase 1 Proteins 0.000 claims 3
• 206010049567 Miller Fisher syndrome Diseases 0.000 claims 3
• 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 claims 3
• 208000037538 Myelomonocytic Juvenile Leukemia Diseases 0.000 claims 3
• 208000000733 Paroxysmal Hemoglobinuria Diseases 0.000 claims 3
• 206010034277 Pemphigoid Diseases 0.000 claims 3
• 102100036050 Phosphatidylinositol N-acetylglucosaminyltransferase subunit A Human genes 0.000 claims 3
• 206010014599 encephalitis Diseases 0.000 claims 3
• 208000014951 hematologic disease Diseases 0.000 claims 3
• 201000005992 juvenile myelomonocytic leukemia Diseases 0.000 claims 3
• 201000002215 juvenile rheumatoid arthritis Diseases 0.000 claims 3
• 201000006417 multiple sclerosis Diseases 0.000 claims 3
• 210000000663 muscle cell Anatomy 0.000 claims 3
• 201000003045 paroxysmal nocturnal hemoglobinuria Diseases 0.000 claims 3
• 208000024893 Acute lymphoblastic leukemia Diseases 0.000 claims 2
• 208000014697 Acute lymphocytic leukaemia Diseases 0.000 claims 2
• 208000008190 Agammaglobulinemia Diseases 0.000 claims 2
• 101100339431 Arabidopsis thaliana HMGB2 gene Proteins 0.000 claims 2
• 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 claims 2
• 208000031212 Autoimmune polyendocrinopathy Diseases 0.000 claims 2
• 208000009299 Benign Mucous Membrane Pemphigoid Diseases 0.000 claims 2
• 102100035875 C-C chemokine receptor type 5 Human genes 0.000 claims 2
• 101710149870 C-C chemokine receptor type 5 Proteins 0.000 claims 2
• 102100031650 C-X-C chemokine receptor type 4 Human genes 0.000 claims 2
• 101150069031 CSN2 gene Proteins 0.000 claims 2
• 108700004991 Cas12a Proteins 0.000 claims 2
• 102100034229 Citramalyl-CoA lyase, mitochondrial Human genes 0.000 claims 2
• 206010053138 Congenital aplastic anaemia Diseases 0.000 claims 2
• 102100025621 Cytochrome b-245 heavy chain Human genes 0.000 claims 2
• 101150048676 FUT1 gene Proteins 0.000 claims 2
• 102100039835 Galactoside alpha-(1,2)-fucosyltransferase 1 Human genes 0.000 claims 2
• 208000035895 Guillain-Barré syndrome Diseases 0.000 claims 2
• 108700010013 HMGB1 Proteins 0.000 claims 2
• 208000035186 Hemolytic Autoimmune Anemia Diseases 0.000 claims 2
• 102100037907 High mobility group protein B1 Human genes 0.000 claims 2
• 101000922348 Homo sapiens C-X-C chemokine receptor type 4 Proteins 0.000 claims 2
• 101000710917 Homo sapiens Citramalyl-CoA lyase, mitochondrial Proteins 0.000 claims 2
• 101000885616 Homo sapiens Galactoside alpha-(1,2)-fucosyltransferase 1 Proteins 0.000 claims 2
• 101001088879 Homo sapiens Lysine-specific demethylase 5D Proteins 0.000 claims 2
• 101000896414 Homo sapiens Nuclear nucleic acid-binding protein C1D Proteins 0.000 claims 2
• 101001043564 Homo sapiens Prolow-density lipoprotein receptor-related protein 1 Proteins 0.000 claims 2
• 208000023105 Huntington disease Diseases 0.000 claims 2
• 206010020983 Hypogammaglobulinaemia Diseases 0.000 claims 2
• 208000010159 IgA glomerulonephritis Diseases 0.000 claims 2
• 206010021263 IgA nephropathy Diseases 0.000 claims 2
• 208000003456 Juvenile Arthritis Diseases 0.000 claims 2
• 101150091012 KDM5D gene Proteins 0.000 claims 2
• 208000012309 Linear IgA disease Diseases 0.000 claims 2
• 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 claims 2
• 102100033143 Lysine-specific demethylase 5D Human genes 0.000 claims 2
• 208000015914 Non-Hodgkin lymphomas Diseases 0.000 claims 2
• 208000018737 Parkinson disease Diseases 0.000 claims 2
• 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 claims 2
• 102100021923 Prolow-density lipoprotein receptor-related protein 1 Human genes 0.000 claims 2
• 208000028017 Psychotic disease Diseases 0.000 claims 2
• 101150108975 Rhd gene Proteins 0.000 claims 2
• 208000006045 Spondylarthropathies Diseases 0.000 claims 2
• 208000031981 Thrombocytopenic Idiopathic Purpura Diseases 0.000 claims 2
• 208000006110 Wiskott-Aldrich syndrome Diseases 0.000 claims 2
• 101150099178 abo gene Proteins 0.000 claims 2
• 208000002552 acute disseminated encephalomyelitis Diseases 0.000 claims 2
• 208000007502 anemia Diseases 0.000 claims 2
• 201000003710 autoimmune thrombocytopenic purpura Diseases 0.000 claims 2
• 210000004413 cardiac myocyte Anatomy 0.000 claims 2
• 208000016532 chronic granulomatous disease Diseases 0.000 claims 2
• 208000032852 chronic lymphocytic leukemia Diseases 0.000 claims 2
• 101150055601 cops2 gene Proteins 0.000 claims 2
• 210000005064 dopaminergic neuron Anatomy 0.000 claims 2
• 101150084157 lrp-1 gene Proteins 0.000 claims 2
• 239000010445 mica Substances 0.000 claims 2
• 229910052618 mica group Inorganic materials 0.000 claims 2
• 201000000050 myeloid neoplasm Diseases 0.000 claims 2
• 230000004770 neurodegeneration Effects 0.000 claims 2
• 208000015122 neurodegenerative disease Diseases 0.000 claims 2
• 229910052703 rhodium Inorganic materials 0.000 claims 2
• 201000000980 schizophrenia Diseases 0.000 claims 2
• 208000002491 severe combined immunodeficiency Diseases 0.000 claims 2
• 210000002363 skeletal muscle cell Anatomy 0.000 claims 2
• 208000011580 syndromic disease Diseases 0.000 claims 2
• 206010043207 temporal arteritis Diseases 0.000 claims 2
• MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 claims 1
• 102100033051 40S ribosomal protein S19 Human genes 0.000 claims 1
• 208000030507 AIDS Diseases 0.000 claims 1
• 102100024643 ATP-binding cassette sub-family D member 1 Human genes 0.000 claims 1
• 206010056508 Acquired epidermolysis bullosa Diseases 0.000 claims 1
• 206010000748 Acute febrile neutrophilic dermatosis Diseases 0.000 claims 1
• 208000032194 Acute haemorrhagic leukoencephalitis Diseases 0.000 claims 1
• 208000026872 Addison Disease Diseases 0.000 claims 1
• 208000002485 Adiposis dolorosa Diseases 0.000 claims 1
• 201000011452 Adrenoleukodystrophy Diseases 0.000 claims 1
• 208000032671 Allergic granulomatous angiitis Diseases 0.000 claims 1
• 206010002556 Ankylosing Spondylitis Diseases 0.000 claims 1
• 208000003343 Antiphospholipid Syndrome Diseases 0.000 claims 1
• 208000001839 Antisynthetase syndrome Diseases 0.000 claims 1
• 208000032467 Aplastic anaemia Diseases 0.000 claims 1
• 206010003645 Atopy Diseases 0.000 claims 1
• 206010071576 Autoimmune aplastic anaemia Diseases 0.000 claims 1
• 206010003827 Autoimmune hepatitis Diseases 0.000 claims 1
• 208000000659 Autoimmune lymphoproliferative syndrome Diseases 0.000 claims 1
• 206010069002 Autoimmune pancreatitis Diseases 0.000 claims 1
• 208000022106 Autoimmune polyendocrinopathy type 2 Diseases 0.000 claims 1
• 201000002827 Balo concentric sclerosis Diseases 0.000 claims 1
• 208000008439 Biliary Liver Cirrhosis Diseases 0.000 claims 1
• 208000033222 Biliary cirrhosis primary Diseases 0.000 claims 1
• 208000033932 Blackfan-Diamond anemia Diseases 0.000 claims 1
• 208000009766 Blau syndrome Diseases 0.000 claims 1
• 201000002829 CREST Syndrome Diseases 0.000 claims 1
• 208000005024 Castleman disease Diseases 0.000 claims 1
• 206010008609 Cholangitis sclerosing Diseases 0.000 claims 1
• 206010008748 Chorea Diseases 0.000 claims 1
• 208000030939 Chronic inflammatory demyelinating polyneuropathy Diseases 0.000 claims 1
• 201000000724 Chronic recurrent multifocal osteomyelitis Diseases 0.000 claims 1
• 208000006344 Churg-Strauss Syndrome Diseases 0.000 claims 1
• 208000031879 Chédiak-Higashi syndrome Diseases 0.000 claims 1
• 208000015943 Coeliac disease Diseases 0.000 claims 1
• 208000010007 Cogan syndrome Diseases 0.000 claims 1
• 208000011038 Cold agglutinin disease Diseases 0.000 claims 1
• 206010009868 Cold type haemolytic anaemia Diseases 0.000 claims 1
• 206010009900 Colitis ulcerative Diseases 0.000 claims 1
• 206010010252 Concentric sclerosis Diseases 0.000 claims 1
• 208000011231 Crohn disease Diseases 0.000 claims 1
• 208000019707 Cryoglobulinemic vasculitis Diseases 0.000 claims 1
• 208000014311 Cushing syndrome Diseases 0.000 claims 1
• 208000016192 Demyelinating disease Diseases 0.000 claims 1
• 201000004624 Dermatitis Diseases 0.000 claims 1
• 206010012468 Dermatitis herpetiformis Diseases 0.000 claims 1
• 201000004449 Diamond-Blackfan anemia Diseases 0.000 claims 1
• 208000004986 Diffuse Cerebral Sclerosis of Schilder Diseases 0.000 claims 1
• 201000003066 Diffuse Scleroderma Diseases 0.000 claims 1
• 208000024134 Diffuse cutaneous systemic sclerosis Diseases 0.000 claims 1
• 208000006926 Discoid Lupus Erythematosus Diseases 0.000 claims 1
• 206010014954 Eosinophilic fasciitis Diseases 0.000 claims 1
• 208000018428 Eosinophilic granulomatosis with polyangiitis Diseases 0.000 claims 1
• 206010015226 Erythema nodosum Diseases 0.000 claims 1
• 208000004332 Evans syndrome Diseases 0.000 claims 1
• 201000004939 Fanconi anemia Diseases 0.000 claims 1
• 102000015212 Fas Ligand Protein Human genes 0.000 claims 1
• 208000007882 Gastritis Diseases 0.000 claims 1
• 206010018364 Glomerulonephritis Diseases 0.000 claims 1
• 208000024869 Goodpasture syndrome Diseases 0.000 claims 1
• 206010072579 Granulomatosis with polyangiitis Diseases 0.000 claims 1
• 208000003807 Graves Disease Diseases 0.000 claims 1
• 208000015023 Graves' disease Diseases 0.000 claims 1
• 208000031220 Hemophilia Diseases 0.000 claims 1
• 208000009292 Hemophilia A Diseases 0.000 claims 1
• 201000004331 Henoch-Schoenlein purpura Diseases 0.000 claims 1
• 206010019617 Henoch-Schonlein purpura Diseases 0.000 claims 1
• 206010019939 Herpes gestationis Diseases 0.000 claims 1
• 208000017604 Hodgkin disease Diseases 0.000 claims 1
• 208000021519 Hodgkin lymphoma Diseases 0.000 claims 1
• 208000010747 Hodgkins lymphoma Diseases 0.000 claims 1
• 206010020751 Hypersensitivity Diseases 0.000 claims 1
• 201000009794 Idiopathic Pulmonary Fibrosis Diseases 0.000 claims 1
• 206010021245 Idiopathic thrombocytopenic purpura Diseases 0.000 claims 1
• 208000031814 IgA Vasculitis Diseases 0.000 claims 1
• 208000014919 IgG4-related retroperitoneal fibrosis Diseases 0.000 claims 1
• 206010052210 Infantile genetic agranulocytosis Diseases 0.000 claims 1
• 208000005615 Interstitial Cystitis Diseases 0.000 claims 1
• 208000000209 Isaacs syndrome Diseases 0.000 claims 1
• 208000011200 Kawasaki disease Diseases 0.000 claims 1
• 201000010743 Lambert-Eaton myasthenic syndrome Diseases 0.000 claims 1
• 201000001779 Leukocyte adhesion deficiency Diseases 0.000 claims 1
• 208000034624 Leukocytoclastic Cutaneous Vasculitis Diseases 0.000 claims 1
• 208000032514 Leukocytoclastic vasculitis Diseases 0.000 claims 1
• 206010024434 Lichen sclerosus Diseases 0.000 claims 1
• 208000000185 Localized scleroderma Diseases 0.000 claims 1
• 208000009777 Majeed syndrome Diseases 0.000 claims 1
• 206010064281 Malignant atrophic papulosis Diseases 0.000 claims 1
• 108010049137 Member 1 Subfamily D ATP Binding Cassette Transporter Proteins 0.000 claims 1
• 208000027530 Meniere disease Diseases 0.000 claims 1
• 208000003250 Mixed connective tissue disease Diseases 0.000 claims 1
• 206010027982 Morphoea Diseases 0.000 claims 1
• 208000012192 Mucous membrane pemphigoid Diseases 0.000 claims 1
• 206010028424 Myasthenic syndrome Diseases 0.000 claims 1
• 201000003793 Myelodysplastic syndrome Diseases 0.000 claims 1
• 201000002481 Myositis Diseases 0.000 claims 1
• 206010072359 Neuromyotonia Diseases 0.000 claims 1
• 208000005225 Opsoclonus-Myoclonus Syndrome Diseases 0.000 claims 1
• 206010053869 POEMS syndrome Diseases 0.000 claims 1
• 206010048705 Paraneoplastic cerebellar degeneration Diseases 0.000 claims 1
• 208000004788 Pars Planitis Diseases 0.000 claims 1
• 208000008223 Pemphigoid Gestationis Diseases 0.000 claims 1
• 201000011152 Pemphigus Diseases 0.000 claims 1
• 241000721454 Pemphigus Species 0.000 claims 1
• 208000000766 Pityriasis Lichenoides Diseases 0.000 claims 1
• 206010048895 Pityriasis lichenoides et varioliformis acuta Diseases 0.000 claims 1
• 206010065159 Polychondritis Diseases 0.000 claims 1
• 208000007048 Polymyalgia Rheumatica Diseases 0.000 claims 1
• 208000012654 Primary biliary cholangitis Diseases 0.000 claims 1
• 208000037534 Progressive hemifacial atrophy Diseases 0.000 claims 1
• 201000004681 Psoriasis Diseases 0.000 claims 1
• 201000001263 Psoriatic Arthritis Diseases 0.000 claims 1
• 208000036824 Psoriatic arthropathy Diseases 0.000 claims 1
• 208000003670 Pure Red-Cell Aplasia Diseases 0.000 claims 1
• 206010037660 Pyrexia Diseases 0.000 claims 1
• 206010071141 Rasmussen encephalitis Diseases 0.000 claims 1
• 208000004160 Rasmussen subacute encephalitis Diseases 0.000 claims 1
• 208000003782 Raynaud disease Diseases 0.000 claims 1
• 208000012322 Raynaud phenomenon Diseases 0.000 claims 1
• 208000033464 Reiter syndrome Diseases 0.000 claims 1
• 208000005793 Restless legs syndrome Diseases 0.000 claims 1
• 206010038979 Retroperitoneal fibrosis Diseases 0.000 claims 1
• 201000010848 Schnitzler Syndrome Diseases 0.000 claims 1
• 206010039705 Scleritis Diseases 0.000 claims 1
• 206010039710 Scleroderma Diseases 0.000 claims 1
• 208000032384 Severe immune-mediated enteropathy Diseases 0.000 claims 1
• 208000021386 Sjogren Syndrome Diseases 0.000 claims 1
• 206010072148 Stiff-Person syndrome Diseases 0.000 claims 1
• 206010042276 Subacute endocarditis Diseases 0.000 claims 1
• 208000002286 Susac Syndrome Diseases 0.000 claims 1
• 208000010265 Sweet syndrome Diseases 0.000 claims 1
• 208000027522 Sydenham chorea Diseases 0.000 claims 1
• 206010042742 Sympathetic ophthalmia Diseases 0.000 claims 1
• 208000012827 T-B+ severe combined immunodeficiency due to gamma chain deficiency Diseases 0.000 claims 1
• 208000001106 Takayasu Arteritis Diseases 0.000 claims 1
• 208000002903 Thalassemia Diseases 0.000 claims 1
• 206010051526 Tolosa-Hunt syndrome Diseases 0.000 claims 1
• 108060008682 Tumor Necrosis Factor Proteins 0.000 claims 1
• 102100040247 Tumor necrosis factor Human genes 0.000 claims 1
• 208000026928 Turner syndrome Diseases 0.000 claims 1
• 201000006704 Ulcerative Colitis Diseases 0.000 claims 1
• 208000025851 Undifferentiated connective tissue disease Diseases 0.000 claims 1
• 208000017379 Undifferentiated connective tissue syndrome Diseases 0.000 claims 1
• 206010046851 Uveitis Diseases 0.000 claims 1
• 206010047115 Vasculitis Diseases 0.000 claims 1
• 206010047642 Vitiligo Diseases 0.000 claims 1
• 208000023940 X-Linked Combined Immunodeficiency disease Diseases 0.000 claims 1
• 201000007146 X-linked severe combined immunodeficiency Diseases 0.000 claims 1
• 208000026935 allergic disease Diseases 0.000 claims 1
• 230000007815 allergy Effects 0.000 claims 1
• 208000004631 alopecia areata Diseases 0.000 claims 1
• 208000010668 atopic eczema Diseases 0.000 claims 1
• 201000004984 autoimmune cardiomyopathy Diseases 0.000 claims 1
• 208000001974 autoimmune enteropathy Diseases 0.000 claims 1
• 201000000448 autoimmune hemolytic anemia Diseases 0.000 claims 1
• 208000027625 autoimmune inner ear disease Diseases 0.000 claims 1
• 201000004339 autoimmune neuropathy Diseases 0.000 claims 1
• 201000005011 autoimmune peripheral neuropathy Diseases 0.000 claims 1
• 201000011385 autoimmune polyendocrine syndrome Diseases 0.000 claims 1
• 201000009780 autoimmune polyendocrine syndrome type 2 Diseases 0.000 claims 1
• 206010071572 autoimmune progesterone dermatitis Diseases 0.000 claims 1
• 208000029407 autoimmune urticaria Diseases 0.000 claims 1
• 201000004982 autoimmune uveitis Diseases 0.000 claims 1
• 208000005980 beta thalassemia Diseases 0.000 claims 1
• 208000000594 bullous pemphigoid Diseases 0.000 claims 1
• 208000019069 chronic childhood arthritis Diseases 0.000 claims 1
• 201000005795 chronic inflammatory demyelinating polyneuritis Diseases 0.000 claims 1
• 208000025302 chronic primary adrenal insufficiency Diseases 0.000 claims 1
• 208000024376 chronic urticaria Diseases 0.000 claims 1
• 201000010002 cicatricial pemphigoid Diseases 0.000 claims 1
• 201000003056 complement component 2 deficiency Diseases 0.000 claims 1
• 201000003278 cryoglobulinemia Diseases 0.000 claims 1
• 208000018261 cutaneous leukocytoclastic angiitis Diseases 0.000 claims 1
• 208000004921 cutaneous lupus erythematosus Diseases 0.000 claims 1
• 206010061811 demyelinating polyneuropathy Diseases 0.000 claims 1
• 201000001981 dermatomyositis Diseases 0.000 claims 1
• 229910003460 diamond Inorganic materials 0.000 claims 1
• 239000010432 diamond Substances 0.000 claims 1
• 201000001564 eosinophilic gastroenteritis Diseases 0.000 claims 1
• 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 claims 1
• 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 claims 1
• 201000011114 epidermolysis bullosa acquisita Diseases 0.000 claims 1
• 208000002980 facial hemiatrophy Diseases 0.000 claims 1
• 210000004700 fetal blood Anatomy 0.000 claims 1
• 230000002496 gastric effect Effects 0.000 claims 1
• 210000001368 germline stem cell Anatomy 0.000 claims 1
• 230000002949 hemolytic effect Effects 0.000 claims 1
• 208000006454 hepatitis Diseases 0.000 claims 1
• 231100000283 hepatitis Toxicity 0.000 claims 1
• 201000006362 hypersensitivity vasculitis Diseases 0.000 claims 1
• 208000015446 immunoglobulin a vasculitis Diseases 0.000 claims 1
• 201000008319 inclusion body myositis Diseases 0.000 claims 1
• 208000036971 interstitial lung disease 2 Diseases 0.000 claims 1
• 201000011486 lichen planus Diseases 0.000 claims 1
• 210000004072 lung Anatomy 0.000 claims 1
• 206010025135 lupus erythematosus Diseases 0.000 claims 1
• 206010063344 microscopic polyangiitis Diseases 0.000 claims 1
• 208000001725 mucocutaneous lymph node syndrome Diseases 0.000 claims 1
• 210000002894 multi-fate stem cell Anatomy 0.000 claims 1
• 206010028417 myasthenia gravis Diseases 0.000 claims 1
• YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 claims 1
• 210000000581 natural killer T-cell Anatomy 0.000 claims 1
• 201000001119 neuropathy Diseases 0.000 claims 1
• 230000007823 neuropathy Effects 0.000 claims 1
• 208000015200 ocular cicatricial pemphigoid Diseases 0.000 claims 1
• 201000005580 palindromic rheumatism Diseases 0.000 claims 1
• 201000001976 pemphigus vulgaris Diseases 0.000 claims 1
• 208000033808 peripheral neuropathy Diseases 0.000 claims 1
• 229920001481 poly(stearyl methacrylate) Polymers 0.000 claims 1
• 201000006292 polyarteritis nodosa Diseases 0.000 claims 1
• 208000005987 polymyositis Diseases 0.000 claims 1
• 201000009395 primary hyperaldosteronism Diseases 0.000 claims 1
• 201000000742 primary sclerosing cholangitis Diseases 0.000 claims 1
• 230000000750 progressive effect Effects 0.000 claims 1
• 208000009954 pyoderma gangrenosum Diseases 0.000 claims 1
• 208000002574 reactive arthritis Diseases 0.000 claims 1
• 208000009169 relapsing polychondritis Diseases 0.000 claims 1
• 206010039073 rheumatoid arthritis Diseases 0.000 claims 1
• 201000000306 sarcoidosis Diseases 0.000 claims 1
• 208000010157 sclerosing cholangitis Diseases 0.000 claims 1
• 208000007056 sickle cell anemia Diseases 0.000 claims 1
• 210000000329 smooth muscle myocyte Anatomy 0.000 claims 1
• 208000008467 subacute bacterial endocarditis Diseases 0.000 claims 1
• 206010043778 thyroiditis Diseases 0.000 claims 1
• 208000009174 transverse myelitis Diseases 0.000 claims 1
• 238000012239 gene modification Methods 0.000 abstract description 4
• 230000005017 genetic modification Effects 0.000 abstract description 4
• 235000013617 genetically modified food Nutrition 0.000 abstract description 4
• 235000018102 proteins Nutrition 0.000 description 28
• 230000004540 complement-dependent cytotoxicity Effects 0.000 description 26
• 238000003556 assay Methods 0.000 description 20
• 238000005516 engineering process Methods 0.000 description 18
• 102000008096 B7-H1 Antigen Human genes 0.000 description 15
• 239000000047 product Substances 0.000 description 11
• 230000007423 decrease Effects 0.000 description 10
• 235000001014 amino acid Nutrition 0.000 description 9
• 229940024606 amino acid Drugs 0.000 description 9
• 239000004074 complement inhibitor Substances 0.000 description 9
• 102000039446 nucleic acids Human genes 0.000 description 9
• 108020004707 nucleic acids Proteins 0.000 description 9
• 150000007523 nucleic acids Chemical class 0.000 description 9
• 230000004083 survival effect Effects 0.000 description 9
• 102100034349 Integrase Human genes 0.000 description 8
• 210000000987 immune system Anatomy 0.000 description 8
• 230000001105 regulatory effect Effects 0.000 description 8
• 108091032973 (ribonucleotides)n+m Proteins 0.000 description 6
• 238000010453 CRISPR/Cas method Methods 0.000 description 6
• 230000022534 cell killing Effects 0.000 description 6
• 229940027941 immunoglobulin g Drugs 0.000 description 6
• 230000002103 transcriptional effect Effects 0.000 description 6
• 238000012546 transfer Methods 0.000 description 6
• 108091026890 Coding region Proteins 0.000 description 5
• 102000052510 DNA-Binding Proteins Human genes 0.000 description 5
• 101710096438 DNA-binding protein Proteins 0.000 description 5
• 108010008532 Deoxyribonuclease I Proteins 0.000 description 5
• 102000007260 Deoxyribonuclease I Human genes 0.000 description 5
• 108020004684 Internal Ribosome Entry Sites Proteins 0.000 description 5
• 108010084498 Myosin Heavy Chains Proteins 0.000 description 5
• 102000005604 Myosin Heavy Chains Human genes 0.000 description 5
• 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 5
• 108010043645 Transcription Activator-Like Effector Nucleases Proteins 0.000 description 5
• 238000006471 dimerization reaction Methods 0.000 description 5
• 230000002068 genetic effect Effects 0.000 description 5
• 230000035772 mutation Effects 0.000 description 5
• 238000002560 therapeutic procedure Methods 0.000 description 5
• 102100026846 Cytidine deaminase Human genes 0.000 description 4
• 108010031325 Cytidine deaminase Proteins 0.000 description 4
• 108060006698 EGF receptor Proteins 0.000 description 4
• 102000004190 Enzymes Human genes 0.000 description 4
• 108090000790 Enzymes Proteins 0.000 description 4
• 108010061833 Integrases Proteins 0.000 description 4
• 102000004459 Nitroreductase Human genes 0.000 description 4
• 101710101148 Probable 6-oxopurine nucleoside phosphorylase Proteins 0.000 description 4
• 102000030764 Purine-nucleoside phosphorylase Human genes 0.000 description 4
• 230000000735 allogeneic effect Effects 0.000 description 4
• 125000000539 amino acid group Chemical class 0.000 description 4
• 238000006243 chemical reaction Methods 0.000 description 4
• 229940088598 enzyme Drugs 0.000 description 4
• XRECTZIEBJDKEO-UHFFFAOYSA-N flucytosine Chemical group NC1=NC(=O)NC=C1F XRECTZIEBJDKEO-UHFFFAOYSA-N 0.000 description 4
• 229960004413 flucytosine Drugs 0.000 description 4
• 108020001507 fusion proteins Proteins 0.000 description 4
• 102000037865 fusion proteins Human genes 0.000 description 4
• 230000005934 immune activation Effects 0.000 description 4
• SEOVTRFCIGRIMH-UHFFFAOYSA-N indole-3-acetic acid Chemical compound C1=CC=C2C(CC(=O)O)=CNC2=C1 SEOVTRFCIGRIMH-UHFFFAOYSA-N 0.000 description 4
• 108020004999 messenger RNA Proteins 0.000 description 4
• 238000010369 molecular cloning Methods 0.000 description 4
• 108020001162 nitroreductase Proteins 0.000 description 4
• 239000002773 nucleotide Substances 0.000 description 4
• 230000002018 overexpression Effects 0.000 description 4
• 230000009467 reduction Effects 0.000 description 4
• 229940124073 Complement inhibitor Drugs 0.000 description 3
• GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 3
• 108010001336 Horseradish Peroxidase Proteins 0.000 description 3
• 108091028043 Nucleic acid sequence Proteins 0.000 description 3
• MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 3
• 108010027179 Tacrolimus Binding Proteins Proteins 0.000 description 3
• 102000018679 Tacrolimus Binding Proteins Human genes 0.000 description 3
• 102100031344 Thioredoxin-interacting protein Human genes 0.000 description 3
• 101710114149 Thioredoxin-interacting protein Proteins 0.000 description 3
• 230000003044 adaptive effect Effects 0.000 description 3
• 238000013459 approach Methods 0.000 description 3
• 230000009286 beneficial effect Effects 0.000 description 3
• 230000015572 biosynthetic process Effects 0.000 description 3
• 230000008859 change Effects 0.000 description 3
• 210000000349 chromosome Anatomy 0.000 description 3
• 230000005782 double-strand break Effects 0.000 description 3
• 239000013604 expression vector Substances 0.000 description 3
• 229960002949 fluorouracil Drugs 0.000 description 3
• 229960002963 ganciclovir Drugs 0.000 description 3
• 230000000670 limiting effect Effects 0.000 description 3
• 230000011987 methylation Effects 0.000 description 3
• 238000007069 methylation reaction Methods 0.000 description 3
• 230000006780 non-homologous end joining Effects 0.000 description 3
• 125000003729 nucleotide group Chemical group 0.000 description 3
• 230000036961 partial effect Effects 0.000 description 3
• 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 3
• 230000008569 process Effects 0.000 description 3
• JJICLMJFIKGAAU-UHFFFAOYSA-M sodium;2-amino-9-(1,3-dihydroxypropan-2-yloxymethyl)purin-6-olate Chemical group [Na+].NC1=NC([O-])=C2N=CN(COC(CO)CO)C2=N1 JJICLMJFIKGAAU-UHFFFAOYSA-M 0.000 description 3
• 210000001519 tissue Anatomy 0.000 description 3
• 230000001960 triggered effect Effects 0.000 description 3
• 102000012758 APOBEC-1 Deaminase Human genes 0.000 description 2
• 108010079649 APOBEC-1 Deaminase Proteins 0.000 description 2
• 102100024222 B-lymphocyte antigen CD19 Human genes 0.000 description 2
• 108010034753 Complement Membrane Attack Complex Proteins 0.000 description 2
• 102000053602 DNA Human genes 0.000 description 2
• 230000033616 DNA repair Effects 0.000 description 2
• 230000004568 DNA-binding Effects 0.000 description 2
• 206010061818 Disease progression Diseases 0.000 description 2
• 108010042407 Endonucleases Proteins 0.000 description 2
• 101900095660 Escherichia coli Cytosine deaminase Proteins 0.000 description 2
• 101000980825 Homo sapiens B-lymphocyte antigen CD19 Proteins 0.000 description 2
• 241000124008 Mammalia Species 0.000 description 2
• 241001465754 Metazoa Species 0.000 description 2
• 102100037499 Parkinson disease protein 7 Human genes 0.000 description 2
• 108010032428 Protein Deglycase DJ-1 Proteins 0.000 description 2
• 241000700159 Rattus Species 0.000 description 2
• ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 2
• 230000021736 acetylation Effects 0.000 description 2
• 238000006640 acetylation reaction Methods 0.000 description 2
• 239000008186 active pharmaceutical agent Substances 0.000 description 2
• 229960000643 adenine Drugs 0.000 description 2
• 238000004458 analytical method Methods 0.000 description 2
• 230000033590 base-excision repair Effects 0.000 description 2
• 230000002759 chromosomal effect Effects 0.000 description 2
• 238000010367 cloning Methods 0.000 description 2
• UHDGCWIWMRVCDJ-ZAKLUEHWSA-N cytidine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-ZAKLUEHWSA-N 0.000 description 2
• OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 2
• 230000009615 deamination Effects 0.000 description 2
• 238000006481 deamination reaction Methods 0.000 description 2
• 230000034994 death Effects 0.000 description 2
• 239000000539 dimer Substances 0.000 description 2
• 230000005750 disease progression Effects 0.000 description 2
• 238000000684 flow cytometry Methods 0.000 description 2
• 230000004927 fusion Effects 0.000 description 2
• 238000001415 gene therapy Methods 0.000 description 2
• 230000013595 glycosylation Effects 0.000 description 2
• 238000006206 glycosylation reaction Methods 0.000 description 2
• 102000044446 human CD46 Human genes 0.000 description 2
• 230000008073 immune recognition Effects 0.000 description 2
• 230000016784 immunoglobulin production Effects 0.000 description 2
• 239000003617 indole-3-acetic acid Substances 0.000 description 2
• 239000000411 inducer Substances 0.000 description 2
• 108091008042 inhibitory receptors Proteins 0.000 description 2
• 238000004519 manufacturing process Methods 0.000 description 2
• 231100000252 nontoxic Toxicity 0.000 description 2
• 230000003000 nontoxic effect Effects 0.000 description 2
• 230000001590 oxidative effect Effects 0.000 description 2
• 230000026731 phosphorylation Effects 0.000 description 2
• 238000006366 phosphorylation reaction Methods 0.000 description 2
• 229920000642 polymer Polymers 0.000 description 2
• 238000003752 polymerase chain reaction Methods 0.000 description 2
• 230000003389 potentiating effect Effects 0.000 description 2
• 230000002062 proliferating effect Effects 0.000 description 2
• 230000010076 replication Effects 0.000 description 2
• 230000004044 response Effects 0.000 description 2
• 238000010839 reverse transcription Methods 0.000 description 2
• 230000005783 single-strand break Effects 0.000 description 2
• 239000000126 substance Substances 0.000 description 2
• 238000006467 substitution reaction Methods 0.000 description 2
• 238000003786 synthesis reaction Methods 0.000 description 2
• 230000009885 systemic effect Effects 0.000 description 2
• 231100000331 toxic Toxicity 0.000 description 2
• 230000002588 toxic effect Effects 0.000 description 2
• 239000003053 toxin Substances 0.000 description 2
• 230000035897 transcription Effects 0.000 description 2
• 238000013518 transcription Methods 0.000 description 2
• 238000013519 translation Methods 0.000 description 2
• 102000040650 (ribonucleotides)n+m Human genes 0.000 description 1
• UHDGCWIWMRVCDJ-UHFFFAOYSA-N 1-beta-D-Xylofuranosyl-NH-Cytosine Natural products O=C1N=C(N)C=CN1C1C(O)C(O)C(CO)O1 UHDGCWIWMRVCDJ-UHFFFAOYSA-N 0.000 description 1
• GOZMBJCYMQQACI-UHFFFAOYSA-N 6,7-dimethyl-3-[[methyl-[2-[methyl-[[1-[3-(trifluoromethyl)phenyl]indol-3-yl]methyl]amino]ethyl]amino]methyl]chromen-4-one;dihydrochloride Chemical compound Cl.Cl.C=1OC2=CC(C)=C(C)C=C2C(=O)C=1CN(C)CCN(C)CC(C1=CC=CC=C11)=CN1C1=CC=CC(C(F)(F)F)=C1 GOZMBJCYMQQACI-UHFFFAOYSA-N 0.000 description 1
• SYMHUEFSSMBHJA-UHFFFAOYSA-N 6-methylpurine Chemical compound CC1=NC=NC2=C1NC=N2 SYMHUEFSSMBHJA-UHFFFAOYSA-N 0.000 description 1
• 230000005730 ADP ribosylation Effects 0.000 description 1
• NSBGUMKAXUXKGI-BPNHAYRBSA-N AP20187 Chemical compound C([C@@H](OC(=O)[C@@H]1CCCCN1C(=O)[C@@H](CC)C=1C=C(OC)C(OC)=C(OC)C=1)C=1C=C(OCC(=O)NCC(CNC(=O)COC=2C=C(C=CC=2)[C@@H](CCC=2C=C(OC)C(OC)=CC=2)OC(=O)[C@H]2N(CCCC2)C(=O)[C@@H](CC)C=2C=C(OC)C(OC)=C(OC)C=2)CN(C)C)C=CC=1)CC1=CC=C(OC)C(OC)=C1 NSBGUMKAXUXKGI-BPNHAYRBSA-N 0.000 description 1
• 229930024421 Adenine Natural products 0.000 description 1
• GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 1
• 241001156002 Anthonomus pomorum Species 0.000 description 1
• 108020005544 Antisense RNA Proteins 0.000 description 1
• 102000017420 CD3 protein, epsilon/gamma/delta subunit Human genes 0.000 description 1
• 108050005493 CD3 protein, epsilon/gamma/delta subunit Proteins 0.000 description 1
• 238000010356 CRISPR-Cas9 genome editing Methods 0.000 description 1
• 241000282472 Canis lupus familiaris Species 0.000 description 1
• 108090000397 Caspase 3 Proteins 0.000 description 1
• 102100029855 Caspase-3 Human genes 0.000 description 1
• 108090000994 Catalytic RNA Proteins 0.000 description 1
• 102000053642 Catalytic RNA Human genes 0.000 description 1
• 241000282693 Cercopithecidae Species 0.000 description 1
• 101710098119 Chaperonin GroEL 2 Proteins 0.000 description 1
• 108020004635 Complementary DNA Proteins 0.000 description 1
• 241000699800 Cricetinae Species 0.000 description 1
• UHDGCWIWMRVCDJ-PSQAKQOGSA-N Cytidine Natural products O=C1N=C(N)C=CN1[C@@H]1[C@@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-PSQAKQOGSA-N 0.000 description 1
• 102000018832 Cytochromes Human genes 0.000 description 1
• 108010052832 Cytochromes Proteins 0.000 description 1
• 101710112752 Cytotoxin Proteins 0.000 description 1
• 230000004543 DNA replication Effects 0.000 description 1
• 230000006820 DNA synthesis Effects 0.000 description 1
• 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 1
• 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 1
• 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 1
• 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 1
• 229920002307 Dextran Polymers 0.000 description 1
• 238000002965 ELISA Methods 0.000 description 1
• 102100031780 Endonuclease Human genes 0.000 description 1
• 102000004533 Endonucleases Human genes 0.000 description 1
• 102220518659 Enhancer of filamentation 1_D10A_mutation Human genes 0.000 description 1
• 241000283086 Equidae Species 0.000 description 1
• 241000282326 Felis catus Species 0.000 description 1
• 241000699694 Gerbillinae Species 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
• 241000282412 Homo Species 0.000 description 1
• 101100386242 Homo sapiens CD55 gene Proteins 0.000 description 1
• 101000983523 Homo sapiens Caspase-9 Proteins 0.000 description 1
• 101000598002 Homo sapiens Interferon regulatory factor 1 Proteins 0.000 description 1
• 101000991060 Homo sapiens MHC class I polypeptide-related sequence A Proteins 0.000 description 1
• 101000914496 Homo sapiens T-cell antigen CD7 Proteins 0.000 description 1
• 101000934346 Homo sapiens T-cell surface antigen CD2 Proteins 0.000 description 1
• 101000716102 Homo sapiens T-cell surface glycoprotein CD4 Proteins 0.000 description 1
• 241000725303 Human immunodeficiency virus Species 0.000 description 1
• 229940076838 Immune checkpoint inhibitor Drugs 0.000 description 1
• 102100037852 Insulin-like growth factor I Human genes 0.000 description 1
• 102000012330 Integrases Human genes 0.000 description 1
• 102100036981 Interferon regulatory factor 1 Human genes 0.000 description 1
• 108010002350 Interleukin-2 Proteins 0.000 description 1
• 102100020873 Interleukin-2 Human genes 0.000 description 1
• 102000004889 Interleukin-6 Human genes 0.000 description 1
• 102100037792 Interleukin-6 receptor subunit alpha Human genes 0.000 description 1
• 102000000704 Interleukin-7 Human genes 0.000 description 1
• 102000004890 Interleukin-8 Human genes 0.000 description 1
• 241000699666 Mus <mouse, genus> Species 0.000 description 1
• 241000699670 Mus sp. Species 0.000 description 1
• 241000282339 Mustela Species 0.000 description 1
• 102100038454 Noggin Human genes 0.000 description 1
• 238000000636 Northern blotting Methods 0.000 description 1
• 108091005461 Nucleic proteins Proteins 0.000 description 1
• 102000015636 Oligopeptides Human genes 0.000 description 1
• 108010038807 Oligopeptides Proteins 0.000 description 1
• 241000283973 Oryctolagus cuniculus Species 0.000 description 1
• 102000010292 Peptide Elongation Factor 1 Human genes 0.000 description 1
• 108010077524 Peptide Elongation Factor 1 Proteins 0.000 description 1
• 102100027913 Peptidyl-prolyl cis-trans isomerase FKBP1A Human genes 0.000 description 1
• 108091000080 Phosphotransferase Proteins 0.000 description 1
• 108020004511 Recombinant DNA Proteins 0.000 description 1
• 102000018120 Recombinases Human genes 0.000 description 1
• 108010091086 Recombinases Proteins 0.000 description 1
• 108010083644 Ribonucleases Proteins 0.000 description 1
• 102000006382 Ribonucleases Human genes 0.000 description 1
• 206010070834 Sensitisation Diseases 0.000 description 1
• 241000700584 Simplexvirus Species 0.000 description 1
• 102100022433 Single-stranded DNA cytosine deaminase Human genes 0.000 description 1
• 101710143275 Single-stranded DNA cytosine deaminase Proteins 0.000 description 1
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
• 241000282887 Suidae Species 0.000 description 1
• 102100027208 T-cell antigen CD7 Human genes 0.000 description 1
• 108010006877 Tacrolimus Binding Protein 1A Proteins 0.000 description 1
• 241000906446 Theraps Species 0.000 description 1
• 108010022394 Threonine synthase Proteins 0.000 description 1
• 102000005497 Thymidylate Synthase Human genes 0.000 description 1
• 102100038313 Transcription factor E2-alpha Human genes 0.000 description 1
• GQLCLPLEEOUJQC-ZTQDTCGGSA-N [(1r)-3-(3,4-dimethoxyphenyl)-1-[3-[2-[2-[[2-[3-[(1r)-3-(3,4-dimethoxyphenyl)-1-[(2s)-1-[(2s)-2-(3,4,5-trimethoxyphenyl)butanoyl]piperidine-2-carbonyl]oxypropyl]phenoxy]acetyl]amino]ethylamino]-2-oxoethoxy]phenyl]propyl] (2s)-1-[(2s)-2-(3,4,5-trimethoxyph Chemical compound C([C@@H](OC(=O)[C@@H]1CCCCN1C(=O)[C@@H](CC)C=1C=C(OC)C(OC)=C(OC)C=1)C=1C=C(OCC(=O)NCCNC(=O)COC=2C=C(C=CC=2)[C@@H](CCC=2C=C(OC)C(OC)=CC=2)OC(=O)[C@H]2N(CCCC2)C(=O)[C@@H](CC)C=2C=C(OC)C(OC)=C(OC)C=2)C=CC=1)CC1=CC=C(OC)C(OC)=C1 GQLCLPLEEOUJQC-ZTQDTCGGSA-N 0.000 description 1
• 230000001594 aberrant effect Effects 0.000 description 1
• 238000002679 ablation Methods 0.000 description 1
• 230000033289 adaptive immune response Effects 0.000 description 1
• 230000000961 alloantigen Effects 0.000 description 1
• 230000000340 anti-metabolite Effects 0.000 description 1
• 239000003429 antifungal agent Substances 0.000 description 1
• 229940100197 antimetabolite Drugs 0.000 description 1
• 239000002256 antimetabolite Substances 0.000 description 1
• 230000000903 blocking effect Effects 0.000 description 1
• 210000001772 blood platelet Anatomy 0.000 description 1
• 239000008366 buffered solution Substances 0.000 description 1
• 238000010804 cDNA synthesis Methods 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
• 230000007910 cell fusion Effects 0.000 description 1
• 210000000170 cell membrane Anatomy 0.000 description 1
• 108091092356 cellular DNA Proteins 0.000 description 1
• 238000012512 characterization method Methods 0.000 description 1
• 238000000975 co-precipitation Methods 0.000 description 1
• 230000004154 complement system Effects 0.000 description 1
• 239000002299 complementary DNA Substances 0.000 description 1
• 239000003184 complementary RNA Substances 0.000 description 1
• 238000007796 conventional method Methods 0.000 description 1
• 238000005520 cutting process Methods 0.000 description 1
• 230000009089 cytolysis Effects 0.000 description 1
• 229940104302 cytosine Drugs 0.000 description 1
• 231100000433 cytotoxic Toxicity 0.000 description 1
• 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 1
• 231100000599 cytotoxic agent Toxicity 0.000 description 1
• 230000001472 cytotoxic effect Effects 0.000 description 1
• 239000002619 cytotoxin Substances 0.000 description 1
• 238000001514 detection method Methods 0.000 description 1
• 230000000447 dimerizing effect Effects 0.000 description 1
• 239000012636 effector Substances 0.000 description 1
• 238000004520 electroporation Methods 0.000 description 1
• 229960000390 fludarabine Drugs 0.000 description 1
• GIUYCYHIANZCFB-FJFJXFQQSA-N fludarabine phosphate Chemical compound C1=NC=2C(N)=NC(F)=NC=2N1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@@H]1O GIUYCYHIANZCFB-FJFJXFQQSA-N 0.000 description 1
• 239000012634 fragment Substances 0.000 description 1
• 238000003197 gene knockdown Methods 0.000 description 1
• 238000010353 genetic engineering Methods 0.000 description 1
• 230000003301 hydrolyzing effect Effects 0.000 description 1
• 230000001900 immune effect Effects 0.000 description 1
• 239000012274 immune-checkpoint protein inhibitor Substances 0.000 description 1
• 230000005847 immunogenicity Effects 0.000 description 1
• 229960003444 immunosuppressant agent Drugs 0.000 description 1
• 230000001976 improved effect Effects 0.000 description 1
• 230000006872 improvement Effects 0.000 description 1
• 238000000338 in vitro Methods 0.000 description 1
• 238000001727 in vivo Methods 0.000 description 1
• 208000033065 inborn errors of immunity Diseases 0.000 description 1
• 230000006882 induction of apoptosis Effects 0.000 description 1
• 230000015788 innate immune response Effects 0.000 description 1
• 239000012212 insulator Substances 0.000 description 1
• 230000002452 interceptive effect Effects 0.000 description 1
• 108040006858 interleukin-6 receptor activity proteins Proteins 0.000 description 1
• 239000000543 intermediate Substances 0.000 description 1
• 230000003834 intracellular effect Effects 0.000 description 1
• 150000002632 lipids Chemical class 0.000 description 1
• 239000002502 liposome Substances 0.000 description 1
• 239000003550 marker Substances 0.000 description 1
• 230000000873 masking effect Effects 0.000 description 1
• 239000000463 material Substances 0.000 description 1
• 239000011159 matrix material Substances 0.000 description 1
• 210000004379 membrane Anatomy 0.000 description 1
• 239000012528 membrane Substances 0.000 description 1
• 239000002207 metabolite Substances 0.000 description 1
• 210000003470 mitochondria Anatomy 0.000 description 1
• 230000005776 mitochondrial apoptotic pathway Effects 0.000 description 1
• 238000002703 mutagenesis Methods 0.000 description 1
• 231100000350 mutagenesis Toxicity 0.000 description 1
• 230000007498 myristoylation Effects 0.000 description 1
• 230000007935 neutral effect Effects 0.000 description 1
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
• 239000002245 particle Substances 0.000 description 1
• 230000037361 pathway Effects 0.000 description 1
• 102000020233 phosphotransferase Human genes 0.000 description 1
• 230000004962 physiological condition Effects 0.000 description 1
• FFNMBRCFFADNAO-UHFFFAOYSA-N pirenzepine hydrochloride Chemical compound [H+].[H+].[Cl-].[Cl-].C1CN(C)CCN1CC(=O)N1C2=NC=CC=C2NC(=O)C2=CC=CC=C21 FFNMBRCFFADNAO-UHFFFAOYSA-N 0.000 description 1
• 239000013600 plasmid vector Substances 0.000 description 1
• 210000004180 plasmocyte Anatomy 0.000 description 1
• 230000008488 polyadenylation Effects 0.000 description 1
• 239000011148 porous material Substances 0.000 description 1
• 230000008092 positive effect Effects 0.000 description 1
• 230000004481 post-translational protein modification Effects 0.000 description 1
• 208000028529 primary immunodeficiency disease Diseases 0.000 description 1
• 230000001681 protective effect Effects 0.000 description 1
• 238000002331 protein detection Methods 0.000 description 1
• 239000013074 reference sample Substances 0.000 description 1
• 102000037983 regulatory factors Human genes 0.000 description 1
• 108091008025 regulatory factors Proteins 0.000 description 1
• 230000008439 repair process Effects 0.000 description 1
• 238000011160 research Methods 0.000 description 1
• 238000012552 review Methods 0.000 description 1
• 108091092562 ribozyme Proteins 0.000 description 1
• 102200015453 rs121912293 Human genes 0.000 description 1
• 239000000523 sample Substances 0.000 description 1
• 230000008313 sensitization Effects 0.000 description 1
• 230000001235 sensitizing effect Effects 0.000 description 1
• 230000009450 sialylation Effects 0.000 description 1
• 229940126586 small molecule drug Drugs 0.000 description 1
• 239000011780 sodium chloride Substances 0.000 description 1
• 125000006850 spacer group Chemical group 0.000 description 1
• 241000894007 species Species 0.000 description 1
• 238000010561 standard procedure Methods 0.000 description 1
• 229940113082 thymine Drugs 0.000 description 1
• 230000001988 toxicity Effects 0.000 description 1
• 231100000419 toxicity Toxicity 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
• 239000013638 trimer Substances 0.000 description 1
• 239000001226 triphosphate Substances 0.000 description 1
• 230000034512 ubiquitination Effects 0.000 description 1
• 238000010798 ubiquitination Methods 0.000 description 1
• 238000011144 upstream manufacturing Methods 0.000 description 1
• 229940035893 uracil Drugs 0.000 description 1
• 239000003981 vehicle Substances 0.000 description 1
• 230000003612 virological effect Effects 0.000 description 1
• 238000001262 western blot Methods 0.000 description 1