IL268110B2 - B-cell engineering - Google Patents
B-cell engineeringInfo
- Publication number
- IL268110B2 IL268110B2 IL268110A IL26811019A IL268110B2 IL 268110 B2 IL268110 B2 IL 268110B2 IL 268110 A IL268110 A IL 268110A IL 26811019 A IL26811019 A IL 26811019A IL 268110 B2 IL268110 B2 IL 268110B2
- Authority
- IL
- Israel
- Prior art keywords
- cell
- cells
- protein
- genetically modified
- transgene
- Prior art date
Links
- 210000003719 b-lymphocyte Anatomy 0.000 title claims description 244
- 210000004027 cell Anatomy 0.000 claims description 173
- 108090000623 proteins and genes Proteins 0.000 claims description 170
- 230000014509 gene expression Effects 0.000 claims description 112
- 108700019146 Transgenes Proteins 0.000 claims description 104
- 102000004169 proteins and genes Human genes 0.000 claims description 100
- 238000000034 method Methods 0.000 claims description 54
- 102100035875 C-C chemokine receptor type 5 Human genes 0.000 claims description 42
- 101710149870 C-C chemokine receptor type 5 Proteins 0.000 claims description 42
- 101001000998 Homo sapiens Protein phosphatase 1 regulatory subunit 12C Proteins 0.000 claims description 33
- 102100035620 Protein phosphatase 1 regulatory subunit 12C Human genes 0.000 claims description 33
- 101000634835 Homo sapiens M1-specific T cell receptor alpha chain Proteins 0.000 claims description 29
- 101000634836 Homo sapiens T cell receptor alpha chain MC.7.G5 Proteins 0.000 claims description 29
- 102100029454 T cell receptor alpha chain MC.7.G5 Human genes 0.000 claims description 29
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 29
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 29
- 230000001225 therapeutic effect Effects 0.000 claims description 28
- 201000010099 disease Diseases 0.000 claims description 19
- 230000004048 modification Effects 0.000 claims description 18
- 238000012986 modification Methods 0.000 claims description 18
- 208000009292 Hemophilia A Diseases 0.000 claims description 17
- 238000003780 insertion Methods 0.000 claims description 16
- 230000037431 insertion Effects 0.000 claims description 16
- 238000002641 enzyme replacement therapy Methods 0.000 claims description 15
- 108091008875 B cell receptors Proteins 0.000 claims description 14
- 208000031220 Hemophilia Diseases 0.000 claims description 14
- 230000002950 deficient Effects 0.000 claims description 14
- 206010028980 Neoplasm Diseases 0.000 claims description 13
- 208000023275 Autoimmune disease Diseases 0.000 claims description 12
- 208000015439 Lysosomal storage disease Diseases 0.000 claims description 12
- 239000003114 blood coagulation factor Substances 0.000 claims description 12
- 210000001280 germinal center Anatomy 0.000 claims description 12
- 102000015081 Blood Coagulation Factors Human genes 0.000 claims description 11
- 108010039209 Blood Coagulation Factors Proteins 0.000 claims description 11
- 108010088751 Albumins Proteins 0.000 claims description 10
- 208000035475 disorder Diseases 0.000 claims description 10
- 201000011510 cancer Diseases 0.000 claims description 9
- 244000052769 pathogen Species 0.000 claims description 8
- 102000009027 Albumins Human genes 0.000 claims description 7
- 238000012217 deletion Methods 0.000 claims description 7
- 230000037430 deletion Effects 0.000 claims description 7
- 230000001629 suppression Effects 0.000 claims description 7
- 102100022641 Coagulation factor IX Human genes 0.000 claims description 6
- 208000015181 infectious disease Diseases 0.000 claims description 6
- 108010076282 Factor IX Proteins 0.000 claims description 5
- 230000008614 cellular interaction Effects 0.000 claims description 5
- 229960004222 factor ix Drugs 0.000 claims description 5
- 210000003958 hematopoietic stem cell Anatomy 0.000 claims description 5
- 230000001717 pathogenic effect Effects 0.000 claims description 5
- 230000005875 antibody response Effects 0.000 claims description 4
- 230000003915 cell function Effects 0.000 claims description 4
- BSDCIRGNJKZPFV-GWOFURMSSA-N (2r,3s,4r,5r)-2-(hydroxymethyl)-5-(2,5,6-trichlorobenzimidazol-1-yl)oxolane-3,4-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=CC(Cl)=C(Cl)C=C2N=C1Cl BSDCIRGNJKZPFV-GWOFURMSSA-N 0.000 claims description 3
- 101000763322 Homo sapiens M1-specific T cell receptor beta chain Proteins 0.000 claims description 3
- 101000763321 Homo sapiens T cell receptor beta chain MC.7.G5 Proteins 0.000 claims description 3
- 102100026967 T cell receptor beta chain MC.7.G5 Human genes 0.000 claims description 3
- 230000033228 biological regulation Effects 0.000 claims description 3
- 230000008499 blood brain barrier function Effects 0.000 claims description 3
- 210000001218 blood-brain barrier Anatomy 0.000 claims description 3
- 230000002401 inhibitory effect Effects 0.000 claims description 3
- 239000002243 precursor Substances 0.000 claims description 3
- 235000011449 Rosa Nutrition 0.000 claims description 2
- 210000002707 regulatory b cell Anatomy 0.000 claims description 2
- 230000001455 anti-clotting effect Effects 0.000 claims 1
- 230000006023 anti-tumor response Effects 0.000 claims 1
- 101710163270 Nuclease Proteins 0.000 description 70
- 239000005090 green fluorescent protein Substances 0.000 description 52
- 108010017070 Zinc Finger Nucleases Proteins 0.000 description 50
- 239000013598 vector Substances 0.000 description 48
- 108020004999 messenger RNA Proteins 0.000 description 39
- 230000010354 integration Effects 0.000 description 38
- 150000007523 nucleic acids Chemical class 0.000 description 31
- 238000004520 electroporation Methods 0.000 description 30
- 102000039446 nucleic acids Human genes 0.000 description 30
- 108020004707 nucleic acids Proteins 0.000 description 30
- 102000040430 polynucleotide Human genes 0.000 description 28
- 108091033319 polynucleotide Proteins 0.000 description 28
- 239000002157 polynucleotide Substances 0.000 description 28
- 239000000203 mixture Substances 0.000 description 22
- 241000702423 Adeno-associated virus - 2 Species 0.000 description 21
- 238000003776 cleavage reaction Methods 0.000 description 21
- 102000004196 processed proteins & peptides Human genes 0.000 description 21
- 230000007017 scission Effects 0.000 description 21
- 108020004414 DNA Proteins 0.000 description 20
- 229920001184 polypeptide Polymers 0.000 description 19
- 230000001404 mediated effect Effects 0.000 description 17
- 239000002773 nucleotide Substances 0.000 description 17
- 125000003729 nucleotide group Chemical group 0.000 description 17
- 239000000047 product Substances 0.000 description 17
- 239000013607 AAV vector Substances 0.000 description 16
- 238000004519 manufacturing process Methods 0.000 description 16
- 230000003612 virological effect Effects 0.000 description 15
- OZFAFGSSMRRTDW-UHFFFAOYSA-N (2,4-dichlorophenyl) benzenesulfonate Chemical compound ClC1=CC(Cl)=CC=C1OS(=O)(=O)C1=CC=CC=C1 OZFAFGSSMRRTDW-UHFFFAOYSA-N 0.000 description 14
- 102000011755 Phosphoglycerate Kinase Human genes 0.000 description 14
- 101001099217 Thermotoga maritima (strain ATCC 43589 / DSM 3109 / JCM 10099 / NBRC 100826 / MSB8) Triosephosphate isomerase Proteins 0.000 description 14
- 241000700605 Viruses Species 0.000 description 14
- 239000000427 antigen Substances 0.000 description 14
- 230000006870 function Effects 0.000 description 14
- 238000001727 in vivo Methods 0.000 description 14
- 210000003720 plasmablast Anatomy 0.000 description 14
- 239000013612 plasmid Substances 0.000 description 14
- 210000004180 plasmocyte Anatomy 0.000 description 14
- 239000013603 viral vector Substances 0.000 description 14
- 102000004127 Cytokines Human genes 0.000 description 13
- 108090000695 Cytokines Proteins 0.000 description 13
- 238000004113 cell culture Methods 0.000 description 13
- 239000012591 Dulbecco’s Phosphate Buffered Saline Substances 0.000 description 12
- 239000003623 enhancer Substances 0.000 description 12
- 238000000338 in vitro Methods 0.000 description 12
- 230000002441 reversible effect Effects 0.000 description 12
- 239000006228 supernatant Substances 0.000 description 12
- 238000011282 treatment Methods 0.000 description 12
- 102000004190 Enzymes Human genes 0.000 description 11
- 108090000790 Enzymes Proteins 0.000 description 11
- 108091007433 antigens Proteins 0.000 description 11
- 102000036639 antigens Human genes 0.000 description 11
- 229940088598 enzyme Drugs 0.000 description 11
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 10
- 108010077544 Chromatin Proteins 0.000 description 10
- 108091026890 Coding region Proteins 0.000 description 10
- 238000002965 ELISA Methods 0.000 description 10
- 210000001744 T-lymphocyte Anatomy 0.000 description 10
- 210000003483 chromatin Anatomy 0.000 description 10
- 230000000694 effects Effects 0.000 description 10
- 238000010362 genome editing Methods 0.000 description 10
- -1 monobody Proteins 0.000 description 10
- 239000002105 nanoparticle Substances 0.000 description 10
- 210000004369 blood Anatomy 0.000 description 9
- 239000008280 blood Substances 0.000 description 9
- 238000002474 experimental method Methods 0.000 description 9
- 230000016784 immunoglobulin production Effects 0.000 description 9
- 150000002632 lipids Chemical class 0.000 description 9
- 210000000130 stem cell Anatomy 0.000 description 9
- 210000001519 tissue Anatomy 0.000 description 9
- 238000010361 transduction Methods 0.000 description 9
- 230000026683 transduction Effects 0.000 description 9
- 238000000684 flow cytometry Methods 0.000 description 8
- 230000008569 process Effects 0.000 description 8
- 230000002103 transcriptional effect Effects 0.000 description 8
- 238000012546 transfer Methods 0.000 description 8
- 241000972680 Adeno-associated virus - 6 Species 0.000 description 7
- 230000003844 B-cell-activation Effects 0.000 description 7
- 102000002464 Galactosidases Human genes 0.000 description 7
- 108010093031 Galactosidases Proteins 0.000 description 7
- 108010017544 Glucosylceramidase Proteins 0.000 description 7
- 102000004547 Glucosylceramidase Human genes 0.000 description 7
- 102000004627 Iduronidase Human genes 0.000 description 7
- 108010003381 Iduronidase Proteins 0.000 description 7
- 102100026263 Sphingomyelin phosphodiesterase Human genes 0.000 description 7
- 238000012350 deep sequencing Methods 0.000 description 7
- 230000004927 fusion Effects 0.000 description 7
- 108020001507 fusion proteins Proteins 0.000 description 7
- 102000037865 fusion proteins Human genes 0.000 description 7
- 238000001415 gene therapy Methods 0.000 description 7
- 210000001165 lymph node Anatomy 0.000 description 7
- 230000035772 mutation Effects 0.000 description 7
- 230000006780 non-homologous end joining Effects 0.000 description 7
- 230000001105 regulatory effect Effects 0.000 description 7
- 210000000952 spleen Anatomy 0.000 description 7
- 238000010453 CRISPR/Cas method Methods 0.000 description 6
- 230000004568 DNA-binding Effects 0.000 description 6
- 208000026350 Inborn Genetic disease Diseases 0.000 description 6
- 101710201924 Sphingomyelin phosphodiesterase 1 Proteins 0.000 description 6
- 101710095280 Sphingomyelinase C 1 Proteins 0.000 description 6
- 230000001413 cellular effect Effects 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 210000000349 chromosome Anatomy 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- 239000012634 fragment Substances 0.000 description 6
- 238000012239 gene modification Methods 0.000 description 6
- 208000016361 genetic disease Diseases 0.000 description 6
- 230000006801 homologous recombination Effects 0.000 description 6
- 238000002744 homologous recombination Methods 0.000 description 6
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 6
- 238000004806 packaging method and process Methods 0.000 description 6
- 102000005962 receptors Human genes 0.000 description 6
- 108020003175 receptors Proteins 0.000 description 6
- 230000006798 recombination Effects 0.000 description 6
- 238000005215 recombination Methods 0.000 description 6
- 230000008685 targeting Effects 0.000 description 6
- 108091093088 Amplicon Proteins 0.000 description 5
- 108010054218 Factor VIII Proteins 0.000 description 5
- 102000001690 Factor VIII Human genes 0.000 description 5
- 101000911390 Homo sapiens Coagulation factor VIII Proteins 0.000 description 5
- 101710096421 Iduronate 2-sulfatase Proteins 0.000 description 5
- 102100029199 Iduronate 2-sulfatase Human genes 0.000 description 5
- 102000003814 Interleukin-10 Human genes 0.000 description 5
- 108090000174 Interleukin-10 Proteins 0.000 description 5
- 238000010459 TALEN Methods 0.000 description 5
- 108010043645 Transcription Activator-Like Effector Nucleases Proteins 0.000 description 5
- 150000001413 amino acids Chemical class 0.000 description 5
- 238000011161 development Methods 0.000 description 5
- 230000018109 developmental process Effects 0.000 description 5
- 230000034431 double-strand break repair via homologous recombination Effects 0.000 description 5
- 229940076144 interleukin-10 Drugs 0.000 description 5
- 239000002502 liposome Substances 0.000 description 5
- 239000003550 marker Substances 0.000 description 5
- 210000003519 mature b lymphocyte Anatomy 0.000 description 5
- 239000002245 particle Substances 0.000 description 5
- 230000008488 polyadenylation Effects 0.000 description 5
- 210000001948 pro-b lymphocyte Anatomy 0.000 description 5
- 230000010076 replication Effects 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 230000001052 transient effect Effects 0.000 description 5
- 241000701161 unidentified adenovirus Species 0.000 description 5
- 108010033918 Alanine-glyoxylate transaminase Proteins 0.000 description 4
- 102000007610 Amino-acid N-acetyltransferase Human genes 0.000 description 4
- 108010032178 Amino-acid N-acetyltransferase Proteins 0.000 description 4
- 108700040066 Argininosuccinate lyases Proteins 0.000 description 4
- 102000037115 Carbamoyl-phosphate synthase (ammonia) Human genes 0.000 description 4
- 108090000447 Carbamoyl-phosphate synthase (ammonia) Proteins 0.000 description 4
- 102100026735 Coagulation factor VIII Human genes 0.000 description 4
- 206010053567 Coagulopathies Diseases 0.000 description 4
- 208000015872 Gaucher disease Diseases 0.000 description 4
- 102000003638 Glucose-6-Phosphatase Human genes 0.000 description 4
- 108010086800 Glucose-6-Phosphatase Proteins 0.000 description 4
- 102100030648 Glyoxylate reductase/hydroxypyruvate reductase Human genes 0.000 description 4
- 101710200205 Glyoxylate reductase/hydroxypyruvate reductase Proteins 0.000 description 4
- 108010000487 High-Molecular-Weight Kininogen Proteins 0.000 description 4
- 102100035792 Kininogen-1 Human genes 0.000 description 4
- 108010001831 LDL receptors Proteins 0.000 description 4
- 241000713666 Lentivirus Species 0.000 description 4
- 102000003960 Ligases Human genes 0.000 description 4
- 108090000364 Ligases Proteins 0.000 description 4
- 102100024640 Low-density lipoprotein receptor Human genes 0.000 description 4
- 108090000856 Lyases Proteins 0.000 description 4
- 102000004317 Lyases Human genes 0.000 description 4
- 208000002678 Mucopolysaccharidoses Diseases 0.000 description 4
- 102000007981 Ornithine carbamoyltransferase Human genes 0.000 description 4
- 101710198224 Ornithine carbamoyltransferase, mitochondrial Proteins 0.000 description 4
- 108010069013 Phenylalanine Hydroxylase Proteins 0.000 description 4
- 102100038223 Phenylalanine-4-hydroxylase Human genes 0.000 description 4
- 102100026842 Serine-pyruvate aminotransferase Human genes 0.000 description 4
- 108091023040 Transcription factor Proteins 0.000 description 4
- 102000040945 Transcription factor Human genes 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 230000004913 activation Effects 0.000 description 4
- 229940024606 amino acid Drugs 0.000 description 4
- 210000000612 antigen-presenting cell Anatomy 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- 230000007812 deficiency Effects 0.000 description 4
- 230000004069 differentiation Effects 0.000 description 4
- 230000005017 genetic modification Effects 0.000 description 4
- 235000013617 genetically modified food Nutrition 0.000 description 4
- 230000028993 immune response Effects 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 230000002147 killing effect Effects 0.000 description 4
- 210000004185 liver Anatomy 0.000 description 4
- 230000007246 mechanism Effects 0.000 description 4
- 206010028093 mucopolysaccharidosis Diseases 0.000 description 4
- 239000008194 pharmaceutical composition Substances 0.000 description 4
- 108010025221 plasma protein Z Proteins 0.000 description 4
- 229920000642 polymer Polymers 0.000 description 4
- 230000002265 prevention Effects 0.000 description 4
- 230000004044 response Effects 0.000 description 4
- 230000028327 secretion Effects 0.000 description 4
- 108010060800 serine-pyruvate aminotransferase Proteins 0.000 description 4
- 230000035939 shock Effects 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 238000002560 therapeutic procedure Methods 0.000 description 4
- 238000001890 transfection Methods 0.000 description 4
- 230000014616 translation Effects 0.000 description 4
- 241001634120 Adeno-associated virus - 5 Species 0.000 description 3
- 241001164825 Adeno-associated virus - 8 Species 0.000 description 3
- 102100024222 B-lymphocyte antigen CD19 Human genes 0.000 description 3
- 108010008532 Deoxyribonuclease I Proteins 0.000 description 3
- 102000007260 Deoxyribonuclease I Human genes 0.000 description 3
- 102100025012 Dipeptidyl peptidase 4 Human genes 0.000 description 3
- 108010042407 Endonucleases Proteins 0.000 description 3
- 102000004533 Endonucleases Human genes 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 201000003542 Factor VIII deficiency Diseases 0.000 description 3
- 108010080865 Factor XII Proteins 0.000 description 3
- 102000000429 Factor XII Human genes 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 102000003886 Glycoproteins Human genes 0.000 description 3
- 108090000288 Glycoproteins Proteins 0.000 description 3
- 101000980825 Homo sapiens B-lymphocyte antigen CD19 Proteins 0.000 description 3
- 102100023915 Insulin Human genes 0.000 description 3
- 108090001061 Insulin Proteins 0.000 description 3
- 108090001030 Lipoproteins Proteins 0.000 description 3
- 102000004895 Lipoproteins Human genes 0.000 description 3
- 102100033448 Lysosomal alpha-glucosidase Human genes 0.000 description 3
- 206010056886 Mucopolysaccharidosis I Diseases 0.000 description 3
- 206010033128 Ovarian cancer Diseases 0.000 description 3
- 108700019535 Phosphoprotein Phosphatases Proteins 0.000 description 3
- 108010060818 Toll-Like Receptor 9 Proteins 0.000 description 3
- 102100033117 Toll-like receptor 9 Human genes 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 210000001185 bone marrow Anatomy 0.000 description 3
- AIYUHDOJVYHVIT-UHFFFAOYSA-M caesium chloride Chemical compound [Cl-].[Cs+] AIYUHDOJVYHVIT-UHFFFAOYSA-M 0.000 description 3
- 210000000234 capsid Anatomy 0.000 description 3
- 230000011712 cell development Effects 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- 206010012601 diabetes mellitus Diseases 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 229960000301 factor viii Drugs 0.000 description 3
- 230000002068 genetic effect Effects 0.000 description 3
- 210000002865 immune cell Anatomy 0.000 description 3
- 230000002779 inactivation Effects 0.000 description 3
- 239000012212 insulator Substances 0.000 description 3
- 229940125396 insulin Drugs 0.000 description 3
- 239000003446 ligand Substances 0.000 description 3
- 230000002062 proliferating effect Effects 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 230000001177 retroviral effect Effects 0.000 description 3
- 206010039073 rheumatoid arthritis Diseases 0.000 description 3
- 208000007056 sickle cell anemia Diseases 0.000 description 3
- 230000000392 somatic effect Effects 0.000 description 3
- 230000000638 stimulation Effects 0.000 description 3
- 230000004083 survival effect Effects 0.000 description 3
- 208000011580 syndromic disease Diseases 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 2
- KISWVXRQTGLFGD-UHFFFAOYSA-N 2-[[2-[[6-amino-2-[[2-[[2-[[5-amino-2-[[2-[[1-[2-[[6-amino-2-[(2,5-diamino-5-oxopentanoyl)amino]hexanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]-5-(diaminomethylideneamino)p Chemical compound C1CCN(C(=O)C(CCCN=C(N)N)NC(=O)C(CCCCN)NC(=O)C(N)CCC(N)=O)C1C(=O)NC(CO)C(=O)NC(CCC(N)=O)C(=O)NC(CCCN=C(N)N)C(=O)NC(CO)C(=O)NC(CCCCN)C(=O)NC(C(=O)NC(CC(C)C)C(O)=O)CC1=CC=C(O)C=C1 KISWVXRQTGLFGD-UHFFFAOYSA-N 0.000 description 2
- GACSIVHAIFQKTC-OWOJBTEDSA-N 4-fumarylacetoacetic acid Chemical compound OC(=O)CC(=O)CC(=O)\C=C\C(O)=O GACSIVHAIFQKTC-OWOJBTEDSA-N 0.000 description 2
- MXCVHSXCXPHOLP-UHFFFAOYSA-N 4-oxo-6-propylchromene-2-carboxylic acid Chemical compound O1C(C(O)=O)=CC(=O)C2=CC(CCC)=CC=C21 MXCVHSXCXPHOLP-UHFFFAOYSA-N 0.000 description 2
- 241001655883 Adeno-associated virus - 1 Species 0.000 description 2
- 241000202702 Adeno-associated virus - 3 Species 0.000 description 2
- 241000580270 Adeno-associated virus - 4 Species 0.000 description 2
- 108020005544 Antisense RNA Proteins 0.000 description 2
- 102000004411 Antithrombin III Human genes 0.000 description 2
- 108090000935 Antithrombin III Proteins 0.000 description 2
- 102000018616 Apolipoproteins B Human genes 0.000 description 2
- 108010027006 Apolipoproteins B Proteins 0.000 description 2
- 102000004452 Arginase Human genes 0.000 description 2
- 102100021723 Arginase-1 Human genes 0.000 description 2
- 108700024123 Arginases Proteins 0.000 description 2
- 102000009042 Argininosuccinate Lyase Human genes 0.000 description 2
- 102100021631 B-cell lymphoma 6 protein Human genes 0.000 description 2
- 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- 102100022548 Beta-hexosaminidase subunit alpha Human genes 0.000 description 2
- 108091033409 CRISPR Proteins 0.000 description 2
- 238000010354 CRISPR gene editing Methods 0.000 description 2
- 102100034279 Calcium-binding mitochondrial carrier protein Aralar2 Human genes 0.000 description 2
- 108010078791 Carrier Proteins Proteins 0.000 description 2
- 102100023804 Coagulation factor VII Human genes 0.000 description 2
- 102100023470 Cobalamin trafficking protein CblD Human genes 0.000 description 2
- 206010010099 Combined immunodeficiency Diseases 0.000 description 2
- 108020004635 Complementary DNA Proteins 0.000 description 2
- 102100027591 Copper-transporting ATPase 2 Human genes 0.000 description 2
- 102100023376 Corrinoid adenosyltransferase Human genes 0.000 description 2
- 101710164985 Cyanocobalamin reductase / alkylcobalamin dealkylase Proteins 0.000 description 2
- 102100023381 Cyanocobalamin reductase / alkylcobalamin dealkylase Human genes 0.000 description 2
- NBSCHQHZLSJFNQ-GASJEMHNSA-N D-Glucose 6-phosphate Chemical compound OC1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H](O)[C@H]1O NBSCHQHZLSJFNQ-GASJEMHNSA-N 0.000 description 2
- 102000052510 DNA-Binding Proteins Human genes 0.000 description 2
- 108700020911 DNA-Binding Proteins Proteins 0.000 description 2
- 208000024720 Fabry Disease Diseases 0.000 description 2
- 108010014172 Factor V Proteins 0.000 description 2
- 108010023321 Factor VII Proteins 0.000 description 2
- 108010014173 Factor X Proteins 0.000 description 2
- 108010074864 Factor XI Proteins 0.000 description 2
- 108010071289 Factor XIII Proteins 0.000 description 2
- 108010049003 Fibrinogen Proteins 0.000 description 2
- 102000008946 Fibrinogen Human genes 0.000 description 2
- 102100037362 Fibronectin Human genes 0.000 description 2
- 108010067306 Fibronectins Proteins 0.000 description 2
- VFRROHXSMXFLSN-UHFFFAOYSA-N Glc6P Natural products OP(=O)(O)OCC(O)C(O)C(O)C(O)C=O VFRROHXSMXFLSN-UHFFFAOYSA-N 0.000 description 2
- 206010053185 Glycogen storage disease type II Diseases 0.000 description 2
- 208000015023 Graves' disease Diseases 0.000 description 2
- 108020005004 Guide RNA Proteins 0.000 description 2
- 108090000481 Heparin Cofactor II Proteins 0.000 description 2
- 102100030500 Heparin cofactor 2 Human genes 0.000 description 2
- 101000752037 Homo sapiens Arginase-1 Proteins 0.000 description 2
- 101000971234 Homo sapiens B-cell lymphoma 6 protein Proteins 0.000 description 2
- 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 description 2
- 101000977167 Homo sapiens Cobalamin trafficking protein CblD Proteins 0.000 description 2
- 101000936280 Homo sapiens Copper-transporting ATPase 2 Proteins 0.000 description 2
- 101001114650 Homo sapiens Corrinoid adenosyltransferase Proteins 0.000 description 2
- 101000941071 Homo sapiens Lysosomal cobalamin transport escort protein LMBD1 Proteins 0.000 description 2
- 101001013648 Homo sapiens Methionine synthase Proteins 0.000 description 2
- 101001116314 Homo sapiens Methionine synthase reductase Proteins 0.000 description 2
- 101001114654 Homo sapiens Methylmalonic aciduria type A protein, mitochondrial Proteins 0.000 description 2
- 101001098982 Homo sapiens Propionyl-CoA carboxylase beta chain, mitochondrial Proteins 0.000 description 2
- 101001098868 Homo sapiens Proprotein convertase subtilisin/kexin type 9 Proteins 0.000 description 2
- 101000800287 Homo sapiens Tubulointerstitial nephritis antigen-like Proteins 0.000 description 2
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 2
- 208000015178 Hurler syndrome Diseases 0.000 description 2
- 108090001042 Hydro-Lyases Proteins 0.000 description 2
- 102000004867 Hydro-Lyases Human genes 0.000 description 2
- 206010061598 Immunodeficiency Diseases 0.000 description 2
- 208000029462 Immunodeficiency disease Diseases 0.000 description 2
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 2
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 2
- 108090001005 Interleukin-6 Proteins 0.000 description 2
- 108020004684 Internal Ribosome Entry Sites Proteins 0.000 description 2
- 108091092195 Intron Proteins 0.000 description 2
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 2
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
- 201000001779 Leukocyte adhesion deficiency Diseases 0.000 description 2
- 102100031335 Lysosomal cobalamin transport escort protein LMBD1 Human genes 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 102100031551 Methionine synthase Human genes 0.000 description 2
- 102100024614 Methionine synthase reductase Human genes 0.000 description 2
- 102100023377 Methylmalonic aciduria type A protein, mitochondrial Human genes 0.000 description 2
- 108010058682 Mitochondrial Proteins Proteins 0.000 description 2
- 102000006404 Mitochondrial Proteins Human genes 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 108091028043 Nucleic acid sequence Proteins 0.000 description 2
- 108091034117 Oligonucleotide Proteins 0.000 description 2
- 108090000113 Plasma Kallikrein Proteins 0.000 description 2
- 102000013566 Plasminogen Human genes 0.000 description 2
- 108010051456 Plasminogen Proteins 0.000 description 2
- 108010022233 Plasminogen Activator Inhibitor 1 Proteins 0.000 description 2
- 102000004179 Plasminogen Activator Inhibitor 2 Human genes 0.000 description 2
- 108090000614 Plasminogen Activator Inhibitor 2 Proteins 0.000 description 2
- 102100039418 Plasminogen activator inhibitor 1 Human genes 0.000 description 2
- 108010071690 Prealbumin Proteins 0.000 description 2
- 102100039025 Propionyl-CoA carboxylase beta chain, mitochondrial Human genes 0.000 description 2
- 102100038955 Proprotein convertase subtilisin/kexin type 9 Human genes 0.000 description 2
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 2
- 101800004937 Protein C Proteins 0.000 description 2
- 102000017975 Protein C Human genes 0.000 description 2
- 229940096437 Protein S Drugs 0.000 description 2
- 108010066124 Protein S Proteins 0.000 description 2
- 102000029301 Protein S Human genes 0.000 description 2
- 108010094028 Prothrombin Proteins 0.000 description 2
- 102100027378 Prothrombin Human genes 0.000 description 2
- 241000508269 Psidium Species 0.000 description 2
- 101001030849 Rhinella marina Mesotocin receptor Proteins 0.000 description 2
- 108091006207 SLC-Transporter Proteins 0.000 description 2
- 102000037054 SLC-Transporter Human genes 0.000 description 2
- 108091006418 SLC25A13 Proteins 0.000 description 2
- 101800001700 Saposin-D Proteins 0.000 description 2
- 206010039710 Scleroderma Diseases 0.000 description 2
- 102100022433 Single-stranded DNA cytosine deaminase Human genes 0.000 description 2
- 101710143275 Single-stranded DNA cytosine deaminase Proteins 0.000 description 2
- 208000021386 Sjogren Syndrome Diseases 0.000 description 2
- 108010061312 Sphingomyelin Phosphodiesterase Proteins 0.000 description 2
- 208000022292 Tay-Sachs disease Diseases 0.000 description 2
- 208000002903 Thalassemia Diseases 0.000 description 2
- 108010000499 Thromboplastin Proteins 0.000 description 2
- 102000002262 Thromboplastin Human genes 0.000 description 2
- 102000003978 Tissue Plasminogen Activator Human genes 0.000 description 2
- 108090000373 Tissue Plasminogen Activator Proteins 0.000 description 2
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 2
- 102000003990 Urokinase-type plasminogen activator Human genes 0.000 description 2
- 108090000435 Urokinase-type plasminogen activator Proteins 0.000 description 2
- 206010068348 X-linked lymphoproliferative syndrome Diseases 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 102000015395 alpha 1-Antitrypsin Human genes 0.000 description 2
- 108010050122 alpha 1-Antitrypsin Proteins 0.000 description 2
- 229940024142 alpha 1-antitrypsin Drugs 0.000 description 2
- 102000003801 alpha-2-Antiplasmin Human genes 0.000 description 2
- 108090000183 alpha-2-Antiplasmin Proteins 0.000 description 2
- 108010028144 alpha-Glucosidases Proteins 0.000 description 2
- 230000003110 anti-inflammatory effect Effects 0.000 description 2
- 230000005809 anti-tumor immunity Effects 0.000 description 2
- 102000025171 antigen binding proteins Human genes 0.000 description 2
- 108091000831 antigen binding proteins Proteins 0.000 description 2
- 229960005348 antithrombin iii Drugs 0.000 description 2
- 229940009098 aspartate Drugs 0.000 description 2
- 230000001363 autoimmune Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000027455 binding Effects 0.000 description 2
- 210000003995 blood forming stem cell Anatomy 0.000 description 2
- 210000004204 blood vessel Anatomy 0.000 description 2
- 229910000389 calcium phosphate Inorganic materials 0.000 description 2
- 239000001506 calcium phosphate Substances 0.000 description 2
- 235000011010 calcium phosphates Nutrition 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 210000003763 chloroplast Anatomy 0.000 description 2
- 208000016532 chronic granulomatous disease Diseases 0.000 description 2
- 230000035602 clotting Effects 0.000 description 2
- 230000000295 complement effect Effects 0.000 description 2
- 230000002596 correlated effect Effects 0.000 description 2
- 230000000875 corresponding effect Effects 0.000 description 2
- 230000009089 cytolysis Effects 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 210000004443 dendritic cell Anatomy 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 238000000502 dialysis Methods 0.000 description 2
- 230000029087 digestion Effects 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000012636 effector Substances 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 210000001508 eye Anatomy 0.000 description 2
- 201000007219 factor XI deficiency Diseases 0.000 description 2
- 229940012413 factor vii Drugs 0.000 description 2
- 229940012426 factor x Drugs 0.000 description 2
- 230000001605 fetal effect Effects 0.000 description 2
- 229940012952 fibrinogen Drugs 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 229940045189 glucose-6-phosphate Drugs 0.000 description 2
- 229930195712 glutamate Natural products 0.000 description 2
- 201000004502 glycogen storage disease II Diseases 0.000 description 2
- 208000034737 hemoglobinopathy Diseases 0.000 description 2
- 208000009429 hemophilia B Diseases 0.000 description 2
- 210000003297 immature b lymphocyte Anatomy 0.000 description 2
- 230000006058 immune tolerance Effects 0.000 description 2
- 230000007813 immunodeficiency Effects 0.000 description 2
- 230000001506 immunosuppresive effect Effects 0.000 description 2
- 230000008595 infiltration Effects 0.000 description 2
- 238000001764 infiltration Methods 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 208000018337 inherited hemoglobinopathy Diseases 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 238000004255 ion exchange chromatography Methods 0.000 description 2
- 208000032839 leukemia Diseases 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 210000003738 lymphoid progenitor cell Anatomy 0.000 description 2
- 239000006166 lysate Substances 0.000 description 2
- 210000001806 memory b lymphocyte Anatomy 0.000 description 2
- 230000011987 methylation Effects 0.000 description 2
- 238000007069 methylation reaction Methods 0.000 description 2
- 108091070501 miRNA Proteins 0.000 description 2
- 208000022018 mucopolysaccharidosis type 2 Diseases 0.000 description 2
- 210000003205 muscle Anatomy 0.000 description 2
- 238000006386 neutralization reaction Methods 0.000 description 2
- 244000045947 parasite Species 0.000 description 2
- 230000036961 partial effect Effects 0.000 description 2
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 2
- 210000005259 peripheral blood Anatomy 0.000 description 2
- 239000011886 peripheral blood Substances 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 210000002381 plasma Anatomy 0.000 description 2
- 229960000856 protein c Drugs 0.000 description 2
- 229940039716 prothrombin Drugs 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- RXWNCPJZOCPEPQ-NVWDDTSBSA-N puromycin Chemical compound C1=CC(OC)=CC=C1C[C@H](N)C(=O)N[C@H]1[C@@H](O)[C@H](N2C3=NC=NC(=C3N=C2)N(C)C)O[C@@H]1CO RXWNCPJZOCPEPQ-NVWDDTSBSA-N 0.000 description 2
- 230000008707 rearrangement Effects 0.000 description 2
- 230000008439 repair process Effects 0.000 description 2
- 229960004641 rituximab Drugs 0.000 description 2
- 230000011664 signaling Effects 0.000 description 2
- 125000006850 spacer group Chemical group 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 229960000187 tissue plasminogen activator Drugs 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 238000013518 transcription Methods 0.000 description 2
- 230000035897 transcription Effects 0.000 description 2
- 238000013519 translation Methods 0.000 description 2
- 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 2
- 241000701447 unidentified baculovirus Species 0.000 description 2
- 241001430294 unidentified retrovirus Species 0.000 description 2
- 238000011144 upstream manufacturing Methods 0.000 description 2
- 229960005356 urokinase Drugs 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- 108010047303 von Willebrand Factor Proteins 0.000 description 2
- 102100036537 von Willebrand factor Human genes 0.000 description 2
- 229960001134 von willebrand factor Drugs 0.000 description 2
- YRNWIFYIFSBPAU-UHFFFAOYSA-N 4-[4-(dimethylamino)phenyl]-n,n-dimethylaniline Chemical compound C1=CC(N(C)C)=CC=C1C1=CC=C(N(C)C)C=C1 YRNWIFYIFSBPAU-UHFFFAOYSA-N 0.000 description 1
- 230000005730 ADP ribosylation Effects 0.000 description 1
- 102100024643 ATP-binding cassette sub-family D member 1 Human genes 0.000 description 1
- 108010013043 Acetylesterase Proteins 0.000 description 1
- 208000029483 Acquired immunodeficiency Diseases 0.000 description 1
- 201000010028 Acrocephalosyndactylia Diseases 0.000 description 1
- 241001164823 Adeno-associated virus - 7 Species 0.000 description 1
- 208000002485 Adiposis dolorosa Diseases 0.000 description 1
- 201000011452 Adrenoleukodystrophy Diseases 0.000 description 1
- 208000024341 Aicardi syndrome Diseases 0.000 description 1
- 206010002199 Anaphylactic shock Diseases 0.000 description 1
- 206010056292 Androgen-Insensitivity Syndrome Diseases 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 208000025490 Apert syndrome Diseases 0.000 description 1
- 108091023037 Aptamer Proteins 0.000 description 1
- 206010003591 Ataxia Diseases 0.000 description 1
- 102100035634 B-cell linker protein Human genes 0.000 description 1
- 208000003950 B-cell lymphoma Diseases 0.000 description 1
- 108010074708 B7-H1 Antigen Proteins 0.000 description 1
- 201000005943 Barth syndrome Diseases 0.000 description 1
- 208000023328 Basedow disease Diseases 0.000 description 1
- 201000004569 Blindness Diseases 0.000 description 1
- 208000019838 Blood disease Diseases 0.000 description 1
- 208000015885 Blue rubber bleb nevus Diseases 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 102100036166 C-X-C chemokine receptor type 1 Human genes 0.000 description 1
- 102100028989 C-X-C chemokine receptor type 2 Human genes 0.000 description 1
- 102400000432 CD40 ligand, soluble form Human genes 0.000 description 1
- 101800000267 CD40 ligand, soluble form Proteins 0.000 description 1
- 101100356682 Caenorhabditis elegans rho-1 gene Proteins 0.000 description 1
- 208000022526 Canavan disease Diseases 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 108090000565 Capsid Proteins Proteins 0.000 description 1
- 108090000994 Catalytic RNA Proteins 0.000 description 1
- 102000053642 Catalytic RNA Human genes 0.000 description 1
- 102000000844 Cell Surface Receptors Human genes 0.000 description 1
- 108010001857 Cell Surface Receptors Proteins 0.000 description 1
- 206010008342 Cervix carcinoma Diseases 0.000 description 1
- 206010008723 Chondrodystrophy Diseases 0.000 description 1
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 1
- 108020004705 Codon Proteins 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 208000006992 Color Vision Defects Diseases 0.000 description 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
- 206010053138 Congenital aplastic anaemia Diseases 0.000 description 1
- 206010011385 Cri-du-chat syndrome Diseases 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- 201000003883 Cystic fibrosis Diseases 0.000 description 1
- 230000004544 DNA amplification Effects 0.000 description 1
- 102100035925 DNA methyltransferase 1-associated protein 1 Human genes 0.000 description 1
- 230000007018 DNA scission Effects 0.000 description 1
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 1
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 1
- 241000702421 Dependoparvovirus Species 0.000 description 1
- 102000001477 Deubiquitinating Enzymes Human genes 0.000 description 1
- 108010093668 Deubiquitinating Enzymes Proteins 0.000 description 1
- 208000007342 Diabetic Nephropathies Diseases 0.000 description 1
- 206010012689 Diabetic retinopathy Diseases 0.000 description 1
- 206010058314 Dysplasia Diseases 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 101800001467 Envelope glycoprotein E2 Proteins 0.000 description 1
- 206010016077 Factor IX deficiency Diseases 0.000 description 1
- 201000004939 Fanconi anemia Diseases 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 241000724791 Filamentous phage Species 0.000 description 1
- 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 1
- 208000001914 Fragile X syndrome Diseases 0.000 description 1
- 201000011240 Frontotemporal dementia Diseases 0.000 description 1
- 108090001126 Furin Proteins 0.000 description 1
- 102100035233 Furin Human genes 0.000 description 1
- 102000001267 GSK3 Human genes 0.000 description 1
- 208000009796 Gangliosidoses Diseases 0.000 description 1
- 208000020322 Gaucher disease type I Diseases 0.000 description 1
- 108700028146 Genetic Enhancer Elements Proteins 0.000 description 1
- 101000930822 Giardia intestinalis Dipeptidyl-peptidase 4 Proteins 0.000 description 1
- 208000010055 Globoid Cell Leukodystrophy Diseases 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 102000053187 Glucuronidase Human genes 0.000 description 1
- 108010060309 Glucuronidase Proteins 0.000 description 1
- 108010014905 Glycogen Synthase Kinase 3 Proteins 0.000 description 1
- 208000032007 Glycogen storage disease due to acid maltase deficiency Diseases 0.000 description 1
- 229920002683 Glycosaminoglycan Polymers 0.000 description 1
- 208000003807 Graves Disease Diseases 0.000 description 1
- 108010043121 Green Fluorescent Proteins Proteins 0.000 description 1
- 102000004144 Green Fluorescent Proteins Human genes 0.000 description 1
- 102100022662 Guanylyl cyclase C Human genes 0.000 description 1
- 101710198293 Guanylyl cyclase C Proteins 0.000 description 1
- 208000030836 Hashimoto thyroiditis Diseases 0.000 description 1
- 208000018565 Hemochromatosis Diseases 0.000 description 1
- 108010085686 Hemoglobin C Proteins 0.000 description 1
- 102100021519 Hemoglobin subunit beta Human genes 0.000 description 1
- 108091005904 Hemoglobin subunit beta Proteins 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- 208000002972 Hepatolenticular Degeneration Diseases 0.000 description 1
- 102000018713 Histocompatibility Antigens Class II Human genes 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101001045440 Homo sapiens Beta-hexosaminidase subunit alpha Proteins 0.000 description 1
- 101000947174 Homo sapiens C-X-C chemokine receptor type 1 Proteins 0.000 description 1
- 101000930289 Homo sapiens DNA methyltransferase 1-associated protein 1 Proteins 0.000 description 1
- 101000908391 Homo sapiens Dipeptidyl peptidase 4 Proteins 0.000 description 1
- 101000966913 Homo sapiens ELL-associated factor 2 Proteins 0.000 description 1
- 101000851181 Homo sapiens Epidermal growth factor receptor Proteins 0.000 description 1
- 101000615488 Homo sapiens Methyl-CpG-binding domain protein 2 Proteins 0.000 description 1
- 101001109800 Homo sapiens Pro-neuregulin-1, membrane-bound isoform Proteins 0.000 description 1
- 101000684208 Homo sapiens Prolyl endopeptidase FAP Proteins 0.000 description 1
- 108010000521 Human Growth Hormone Proteins 0.000 description 1
- 102000002265 Human Growth Hormone Human genes 0.000 description 1
- 239000000854 Human Growth Hormone Substances 0.000 description 1
- 208000023105 Huntington disease Diseases 0.000 description 1
- 208000025500 Hutchinson-Gilford progeria syndrome Diseases 0.000 description 1
- 241000282620 Hylobates sp. Species 0.000 description 1
- 206010049933 Hypophosphatasia Diseases 0.000 description 1
- 108010091358 Hypoxanthine Phosphoribosyltransferase Proteins 0.000 description 1
- 102100029098 Hypoxanthine-guanine phosphoribosyltransferase Human genes 0.000 description 1
- 108010053927 Iduronate Sulfatase Proteins 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 1
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 1
- 102100029572 Immunoglobulin kappa constant Human genes 0.000 description 1
- 108010090227 Immunoglobulin kappa-Chains Proteins 0.000 description 1
- 206010062016 Immunosuppression Diseases 0.000 description 1
- 208000028547 Inborn Urea Cycle disease Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 108010012621 Inositol-hexakisphosphate kinase Proteins 0.000 description 1
- 102000012330 Integrases Human genes 0.000 description 1
- 108010061833 Integrases Proteins 0.000 description 1
- 108010008212 Integrin alpha4beta1 Proteins 0.000 description 1
- 108010064593 Intercellular Adhesion Molecule-1 Proteins 0.000 description 1
- 102100037877 Intercellular adhesion molecule 1 Human genes 0.000 description 1
- 108010002350 Interleukin-2 Proteins 0.000 description 1
- 108010018951 Interleukin-8B Receptors Proteins 0.000 description 1
- 239000007760 Iscove's Modified Dulbecco's Medium Substances 0.000 description 1
- 208000028226 Krabbe disease Diseases 0.000 description 1
- 206010050638 Langer-Giedion syndrome Diseases 0.000 description 1
- 208000010415 Low Vision Diseases 0.000 description 1
- 108060001084 Luciferase Proteins 0.000 description 1
- 239000005089 Luciferase Substances 0.000 description 1
- 102000006830 Luminescent Proteins Human genes 0.000 description 1
- 108010047357 Luminescent Proteins Proteins 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 102000008072 Lymphokines Human genes 0.000 description 1
- 108010074338 Lymphokines Proteins 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- 208000030289 Lymphoproliferative disease Diseases 0.000 description 1
- 108091054438 MHC class II family Proteins 0.000 description 1
- 208000000916 Mandibulofacial dysostosis Diseases 0.000 description 1
- 208000001826 Marfan syndrome Diseases 0.000 description 1
- 108010049137 Member 1 Subfamily D ATP Binding Cassette Transporter Proteins 0.000 description 1
- 102100021299 Methyl-CpG-binding domain protein 2 Human genes 0.000 description 1
- 108010085747 Methylmalonyl-CoA Decarboxylase Proteins 0.000 description 1
- 108060004795 Methyltransferase Proteins 0.000 description 1
- 108700011259 MicroRNAs Proteins 0.000 description 1
- 201000002983 Mobius syndrome Diseases 0.000 description 1
- 208000034167 Moebius syndrome Diseases 0.000 description 1
- 241000713869 Moloney murine leukemia virus Species 0.000 description 1
- 208000001804 Monosomy 5p Diseases 0.000 description 1
- 208000028781 Mucopolysaccharidosis type 1 Diseases 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 102000008934 Muscle Proteins Human genes 0.000 description 1
- 108010074084 Muscle Proteins Proteins 0.000 description 1
- 108010021466 Mutant Proteins Proteins 0.000 description 1
- 102000008300 Mutant Proteins Human genes 0.000 description 1
- 241000186359 Mycobacterium Species 0.000 description 1
- 201000002481 Myositis Diseases 0.000 description 1
- 208000000175 Nail-Patella Syndrome Diseases 0.000 description 1
- 108091061960 Naked DNA Proteins 0.000 description 1
- 229930193140 Neomycin Natural products 0.000 description 1
- 206010061309 Neoplasm progression Diseases 0.000 description 1
- 208000009905 Neurofibromatoses Diseases 0.000 description 1
- 208000014060 Niemann-Pick disease Diseases 0.000 description 1
- 102000011931 Nucleoproteins Human genes 0.000 description 1
- 108010061100 Nucleoproteins Proteins 0.000 description 1
- 208000022873 Ocular disease Diseases 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 206010031243 Osteogenesis imperfecta Diseases 0.000 description 1
- 208000007571 Ovarian Epithelial Carcinoma Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 238000012408 PCR amplification Methods 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 102000007079 Peptide Fragments Human genes 0.000 description 1
- 108010033276 Peptide Fragments Proteins 0.000 description 1
- 208000018262 Peripheral vascular disease Diseases 0.000 description 1
- 102000045595 Phosphoprotein Phosphatases Human genes 0.000 description 1
- 208000000609 Pick Disease of the Brain Diseases 0.000 description 1
- 208000024571 Pick disease Diseases 0.000 description 1
- 241000224016 Plasmodium Species 0.000 description 1
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 241000097929 Porphyria Species 0.000 description 1
- 208000010642 Porphyrias Diseases 0.000 description 1
- 201000010769 Prader-Willi syndrome Diseases 0.000 description 1
- 208000007932 Progeria Diseases 0.000 description 1
- 102100024216 Programmed cell death 1 ligand 1 Human genes 0.000 description 1
- 102000001253 Protein Kinase Human genes 0.000 description 1
- 108700040121 Protein Methyltransferases Proteins 0.000 description 1
- 102000055027 Protein Methyltransferases Human genes 0.000 description 1
- 208000007531 Proteus syndrome Diseases 0.000 description 1
- 241000125945 Protoparvovirus Species 0.000 description 1
- 101150111584 RHOA gene Proteins 0.000 description 1
- 108091030071 RNAI Proteins 0.000 description 1
- 238000011530 RNeasy Mini Kit Methods 0.000 description 1
- 241000700159 Rattus Species 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
- 208000035415 Reinfection Diseases 0.000 description 1
- 208000033464 Reiter syndrome Diseases 0.000 description 1
- 108700008625 Reporter Genes Proteins 0.000 description 1
- 201000000582 Retinoblastoma Diseases 0.000 description 1
- 208000006289 Rett Syndrome Diseases 0.000 description 1
- 108091028664 Ribonucleotide Proteins 0.000 description 1
- 206010039281 Rubinstein-Taybi syndrome Diseases 0.000 description 1
- 108010017324 STAT3 Transcription Factor Proteins 0.000 description 1
- 229920002684 Sepharose Polymers 0.000 description 1
- 201000004283 Shwachman-Diamond syndrome Diseases 0.000 description 1
- 102100024040 Signal transducer and activator of transcription 3 Human genes 0.000 description 1
- 241000700584 Simplexvirus Species 0.000 description 1
- 108091027967 Small hairpin RNA Proteins 0.000 description 1
- 108020004459 Small interfering RNA Proteins 0.000 description 1
- 201000001388 Smith-Magenis syndrome Diseases 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 208000027077 Stickler syndrome Diseases 0.000 description 1
- 101800001271 Surface protein Proteins 0.000 description 1
- 201000009594 Systemic Scleroderma Diseases 0.000 description 1
- 206010042953 Systemic sclerosis Diseases 0.000 description 1
- 230000006052 T cell proliferation Effects 0.000 description 1
- 108091008874 T cell receptors Proteins 0.000 description 1
- 230000005867 T cell response Effects 0.000 description 1
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 1
- 108010022394 Threonine synthase Proteins 0.000 description 1
- 101710183280 Topoisomerase Proteins 0.000 description 1
- 108010073062 Transcription Activator-Like Effectors Proteins 0.000 description 1
- 108010033576 Transferrin Receptors Proteins 0.000 description 1
- 102100026144 Transferrin receptor protein 1 Human genes 0.000 description 1
- 201000003199 Treacher Collins syndrome Diseases 0.000 description 1
- 208000035378 Trichorhinophalangeal syndrome type 2 Diseases 0.000 description 1
- 208000037280 Trisomy Diseases 0.000 description 1
- 208000026911 Tuberous sclerosis complex Diseases 0.000 description 1
- 208000026928 Turner syndrome Diseases 0.000 description 1
- 102100025038 Ubiquitin carboxyl-terminal hydrolase isozyme L1 Human genes 0.000 description 1
- 101710186825 Ubiquitin carboxyl-terminal hydrolase isozyme L1 Proteins 0.000 description 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
- 241000700618 Vaccinia virus Species 0.000 description 1
- 206010046865 Vaccinia virus infection Diseases 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
- 108020005202 Viral DNA Proteins 0.000 description 1
- 208000026724 Waardenburg syndrome Diseases 0.000 description 1
- 206010049644 Williams syndrome Diseases 0.000 description 1
- 208000018839 Wilson disease Diseases 0.000 description 1
- 208000006110 Wiskott-Aldrich syndrome Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 230000001594 aberrant effect Effects 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- YRKCREAYFQTBPV-UHFFFAOYSA-N acetylacetone Chemical compound CC(=O)CC(C)=O YRKCREAYFQTBPV-UHFFFAOYSA-N 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 208000008919 achondroplasia Diseases 0.000 description 1
- 201000000761 achromatopsia Diseases 0.000 description 1
- 102000010126 acid sphingomyelin phosphodiesterase activity proteins Human genes 0.000 description 1
- 201000009628 adenosine deaminase deficiency Diseases 0.000 description 1
- GFFGJBXGBJISGV-UHFFFAOYSA-N adenyl group Chemical group N1=CN=C2N=CNC2=C1N GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 1
- 239000013566 allergen Substances 0.000 description 1
- 208000006682 alpha 1-Antitrypsin Deficiency Diseases 0.000 description 1
- 201000006288 alpha thalassemia Diseases 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 230000001668 ameliorated effect Effects 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- 229960000723 ampicillin Drugs 0.000 description 1
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 1
- 208000003455 anaphylaxis Diseases 0.000 description 1
- 210000004102 animal cell Anatomy 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000003460 anti-nuclear Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 238000009175 antibody therapy Methods 0.000 description 1
- 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 description 1
- 210000000628 antibody-producing cell Anatomy 0.000 description 1
- 230000005975 antitumor immune response Effects 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 230000003126 arrythmogenic effect Effects 0.000 description 1
- 230000004900 autophagic degradation Effects 0.000 description 1
- 208000036556 autosomal recessive T cell-negative B cell-negative NK cell-negative due to adenosine deaminase deficiency severe combined immunodeficiency Diseases 0.000 description 1
- 208000025341 autosomal recessive disease Diseases 0.000 description 1
- 210000000227 basophil cell of anterior lobe of hypophysis Anatomy 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 208000005980 beta thalassemia Diseases 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 208000034158 bleeding Diseases 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 108010006025 bovine growth hormone Proteins 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 230000007910 cell fusion Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000011748 cell maturation Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000036755 cellular response Effects 0.000 description 1
- 208000015114 central nervous system disease Diseases 0.000 description 1
- 201000010881 cervical cancer Diseases 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 230000002759 chromosomal effect Effects 0.000 description 1
- 208000020832 chronic kidney disease Diseases 0.000 description 1
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 238000000975 co-precipitation Methods 0.000 description 1
- 201000007254 color blindness Diseases 0.000 description 1
- 238000004891 communication Methods 0.000 description 1
- 239000003184 complementary RNA Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 208000011664 congenital factor XI deficiency Diseases 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 230000008094 contradictory effect Effects 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 230000002354 daily effect Effects 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 239000005547 deoxyribonucleotide Substances 0.000 description 1
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 1
- 230000001066 destructive effect Effects 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 208000033679 diabetic kidney disease Diseases 0.000 description 1
- 102000004419 dihydrofolate reductase Human genes 0.000 description 1
- 230000005782 double-strand break Effects 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 208000002169 ectodermal dysplasia Diseases 0.000 description 1
- 208000031068 ectodermal dysplasia syndrome Diseases 0.000 description 1
- 230000013020 embryo development Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 210000000750 endocrine system Anatomy 0.000 description 1
- 108010048367 enhanced green fluorescent protein Proteins 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 229940012444 factor xiii Drugs 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 108091006047 fluorescent proteins Proteins 0.000 description 1
- 102000034287 fluorescent proteins Human genes 0.000 description 1
- 210000000285 follicular dendritic cell Anatomy 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 210000005095 gastrointestinal system Anatomy 0.000 description 1
- 238000012246 gene addition Methods 0.000 description 1
- 230000009368 gene silencing by RNA Effects 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 208000024908 graft versus host disease Diseases 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 210000002443 helper t lymphocyte Anatomy 0.000 description 1
- 208000014951 hematologic disease Diseases 0.000 description 1
- 208000018706 hematopoietic system disease Diseases 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 102000057593 human F8 Human genes 0.000 description 1
- 102000055650 human NRG1 Human genes 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 229960000900 human factor viii Drugs 0.000 description 1
- 230000004727 humoral immunity Effects 0.000 description 1
- 230000037451 immune surveillance Effects 0.000 description 1
- 230000003053 immunization Effects 0.000 description 1
- 238000002649 immunization Methods 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 230000004957 immunoregulator effect Effects 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 230000015788 innate immune response Effects 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 230000000366 juvenile effect Effects 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 210000000014 large pre-b cell Anatomy 0.000 description 1
- 231100001231 less toxic Toxicity 0.000 description 1
- 208000036546 leukodystrophy Diseases 0.000 description 1
- 238000001638 lipofection Methods 0.000 description 1
- 210000005229 liver cell Anatomy 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 208000004731 long QT syndrome Diseases 0.000 description 1
- 201000005296 lung carcinoma Diseases 0.000 description 1
- 210000004324 lymphatic system Anatomy 0.000 description 1
- 230000002934 lysing effect Effects 0.000 description 1
- 108010045758 lysosomal proteins Proteins 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 208000002780 macular degeneration Diseases 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 230000001394 metastastic effect Effects 0.000 description 1
- 206010061289 metastatic neoplasm Diseases 0.000 description 1
- 239000002679 microRNA Substances 0.000 description 1
- 238000000520 microinjection Methods 0.000 description 1
- 210000003470 mitochondria Anatomy 0.000 description 1
- 230000002438 mitochondrial effect Effects 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 201000002273 mucopolysaccharidosis II Diseases 0.000 description 1
- 208000005340 mucopolysaccharidosis III Diseases 0.000 description 1
- 208000011045 mucopolysaccharidosis type 3 Diseases 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 210000000663 muscle cell Anatomy 0.000 description 1
- 239000003471 mutagenic agent Substances 0.000 description 1
- 206010028417 myasthenia gravis Diseases 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 208000031225 myocardial ischemia Diseases 0.000 description 1
- 229960004927 neomycin Drugs 0.000 description 1
- 230000002988 nephrogenic effect Effects 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 201000004931 neurofibromatosis Diseases 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 231100000590 oncogenic Toxicity 0.000 description 1
- 230000002246 oncogenic effect Effects 0.000 description 1
- 210000004789 organ system Anatomy 0.000 description 1
- 210000003463 organelle Anatomy 0.000 description 1
- 239000006179 pH buffering agent Substances 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 230000002688 persistence Effects 0.000 description 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 239000013600 plasmid vector Substances 0.000 description 1
- 229960000502 poloxamer Drugs 0.000 description 1
- 229920001983 poloxamer Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000000644 propagated effect Effects 0.000 description 1
- 235000019833 protease Nutrition 0.000 description 1
- 230000004853 protein function Effects 0.000 description 1
- 108060006633 protein kinase Proteins 0.000 description 1
- 238000009163 protein therapy Methods 0.000 description 1
- 229950010131 puromycin Drugs 0.000 description 1
- 239000013646 rAAV2 vector Substances 0.000 description 1
- 208000002574 reactive arthritis Diseases 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- 108010054624 red fluorescent protein Proteins 0.000 description 1
- 210000003289 regulatory T cell Anatomy 0.000 description 1
- 102000037983 regulatory factors Human genes 0.000 description 1
- 108091008025 regulatory factors Proteins 0.000 description 1
- 238000007634 remodeling Methods 0.000 description 1
- 210000005084 renal tissue Anatomy 0.000 description 1
- 238000009256 replacement therapy Methods 0.000 description 1
- 230000003362 replicative effect Effects 0.000 description 1
- 210000001525 retina Anatomy 0.000 description 1
- 201000003068 rheumatic fever Diseases 0.000 description 1
- 239000002336 ribonucleotide Substances 0.000 description 1
- 125000002652 ribonucleotide group Chemical group 0.000 description 1
- 108091092562 ribozyme Proteins 0.000 description 1
- 230000037390 scarring Effects 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 239000012089 stop solution Substances 0.000 description 1
- 208000023516 stroke disease Diseases 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical group [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 1
- 206010043554 thrombocytopenia Diseases 0.000 description 1
- 210000001685 thyroid gland Anatomy 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 231100000440 toxicity profile Toxicity 0.000 description 1
- 230000002463 transducing effect Effects 0.000 description 1
- 238000003151 transfection method Methods 0.000 description 1
- 201000006532 trichorhinophalangeal syndrome type II Diseases 0.000 description 1
- 208000009999 tuberous sclerosis Diseases 0.000 description 1
- 230000005747 tumor angiogenesis Effects 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 230000005751 tumor progression Effects 0.000 description 1
- 210000003171 tumor-infiltrating lymphocyte Anatomy 0.000 description 1
- 230000034512 ubiquitination Effects 0.000 description 1
- 238000010798 ubiquitination Methods 0.000 description 1
- 238000005199 ultracentrifugation Methods 0.000 description 1
- 208000030954 urea cycle disease Diseases 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 208000007089 vaccinia Diseases 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 230000002861 ventricular Effects 0.000 description 1
- 230000007998 vessel formation Effects 0.000 description 1
- 210000002845 virion Anatomy 0.000 description 1
- 239000000277 virosome Substances 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 239000011534 wash buffer Substances 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- 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
- A61K35/14—Blood; Artificial blood
- A61K35/17—Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes
-
- 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
- A61K35/28—Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
- A61K38/482—Serine endopeptidases (3.4.21)
- A61K38/4846—Factor VII (3.4.21.21); Factor IX (3.4.21.22); Factor Xa (3.4.21.6); Factor XI (3.4.21.27); Factor XII (3.4.21.38)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K40/00—Cellular immunotherapy
- A61K40/10—Cellular immunotherapy characterised by the cell type used
- A61K40/13—B-cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K40/00—Cellular immunotherapy
- A61K40/20—Cellular immunotherapy characterised by the effect or the function of the cells
- A61K40/22—Immunosuppressive or immunotolerising
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K40/00—Cellular immunotherapy
- A61K40/20—Cellular immunotherapy characterised by the effect or the function of the cells
- A61K40/24—Antigen-presenting cells [APC]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K40/00—Cellular immunotherapy
- A61K40/40—Cellular immunotherapy characterised by antigens that are targeted or presented by cells of the immune system
- A61K40/41—Vertebrate antigens
- A61K40/416—Antigens related to auto-immune diseases; Preparations to induce self-tolerance
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/87—Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
- C12N15/90—Stable introduction of foreign DNA into chromosome
- C12N15/902—Stable introduction of foreign DNA into chromosome using homologous recombination
- C12N15/907—Stable introduction of foreign DNA into chromosome using homologous recombination in mammalian cells
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0634—Cells from the blood or the immune system
- C12N5/0635—B lymphocytes
-
- 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
- C12N5/10—Cells modified by introduction of foreign genetic material
- C12N5/12—Fused cells, e.g. hybridomas
- C12N5/16—Animal cells
- C12N5/163—Animal cells one of the fusion partners being a B or a T lymphocyte
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
-
- 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
-
- 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
- C12N2750/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssDNA viruses
- C12N2750/00011—Details
- C12N2750/14011—Parvoviridae
- C12N2750/14111—Dependovirus, e.g. adenoassociated viruses
- C12N2750/14141—Use of virus, viral particle or viral elements as a vector
- C12N2750/14143—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Biomedical Technology (AREA)
- Biotechnology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Zoology (AREA)
- Immunology (AREA)
- Organic Chemistry (AREA)
- Cell Biology (AREA)
- Wood Science & Technology (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- General Engineering & Computer Science (AREA)
- Hematology (AREA)
- Molecular Biology (AREA)
- Microbiology (AREA)
- Biochemistry (AREA)
- Developmental Biology & Embryology (AREA)
- Virology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Plant Pathology (AREA)
- Gastroenterology & Hepatology (AREA)
- Biophysics (AREA)
- Mycology (AREA)
- Physics & Mathematics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Diabetes (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201762450917P | 2017-01-26 | 2017-01-26 | |
| PCT/US2018/015180 WO2018140573A1 (en) | 2017-01-26 | 2018-01-25 | B-cell engineering |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| IL268110A IL268110A (en) | 2019-09-26 |
| IL268110B1 IL268110B1 (en) | 2023-09-01 |
| IL268110B2 true IL268110B2 (en) | 2024-01-01 |
Family
ID=62979713
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL268110A IL268110B2 (en) | 2017-01-26 | 2018-01-25 | B-cell engineering |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US20190352614A1 (enExample) |
| EP (1) | EP3573464A4 (enExample) |
| JP (2) | JP2020505044A (enExample) |
| KR (1) | KR20190111063A (enExample) |
| CN (1) | CN110536963A (enExample) |
| AU (1) | AU2018212652B2 (enExample) |
| BR (1) | BR112019015355A2 (enExample) |
| CA (1) | CA3051113A1 (enExample) |
| IL (1) | IL268110B2 (enExample) |
| MX (1) | MX2019008844A (enExample) |
| WO (1) | WO2018140573A1 (enExample) |
Families Citing this family (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10704021B2 (en) | 2012-03-15 | 2020-07-07 | Flodesign Sonics, Inc. | Acoustic perfusion devices |
| CA2935960C (en) | 2014-01-08 | 2023-01-10 | Bart Lipkens | Acoustophoresis device with dual acoustophoretic chamber |
| US11377651B2 (en) | 2016-10-19 | 2022-07-05 | Flodesign Sonics, Inc. | Cell therapy processes utilizing acoustophoresis |
| US11708572B2 (en) | 2015-04-29 | 2023-07-25 | Flodesign Sonics, Inc. | Acoustic cell separation techniques and processes |
| US11214789B2 (en) | 2016-05-03 | 2022-01-04 | Flodesign Sonics, Inc. | Concentration and washing of particles with acoustics |
| EP3573464A4 (en) * | 2017-01-26 | 2020-12-30 | Sangamo Therapeutics, Inc. | B CELL ENGINEERING |
| AU2018235957B2 (en) * | 2017-03-16 | 2024-02-01 | Seattle Children's Hospital (dba Seattle Children's Research Institute) | Engraftable cell-based immunotherapy for long-term delivery of therapeutic proteins |
| KR20220066413A (ko) | 2017-12-14 | 2022-05-24 | 프로디자인 소닉스, 인크. | 음향 트랜스듀서 구동기 및 제어기 |
| BR112021007301A2 (pt) | 2018-10-18 | 2021-07-27 | Intellia Therapeutics, Inc. | composições e métodos para expressar fator ix |
| WO2021085504A1 (ja) * | 2019-11-01 | 2021-05-06 | 京都府公立大学法人 | Ｂ細胞抗体受容体、及びその利用 |
| EP4127188A4 (en) | 2020-03-31 | 2024-08-21 | Walking Fish Therapeutics | MODIFIED B CELLS AND METHODS OF USE THEREOF |
| WO2023192936A2 (en) * | 2022-03-30 | 2023-10-05 | Fred Hutchinson Cancer Center | Systems and methods to produce b cells that express selected antibodies and gene products |
| WO2024151683A2 (en) * | 2023-01-09 | 2024-07-18 | Walking Fish Therapeutics, Inc. | HUMAN B CELL ENGINEERED TO EXPRESS IgA AND IgM ANTIBODIES FOR THERAPEUTIC USE |
| WO2024196669A2 (en) * | 2023-03-17 | 2024-09-26 | Walking Fish Therapeutics, Inc. | Methods for in vivo editing of b cells |
| WO2024220447A2 (en) * | 2023-04-17 | 2024-10-24 | Be Biopharma, Inc. | Engineered cell preparations for treatment of niemann pick b disease |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20110287532A1 (en) * | 2004-09-22 | 2011-11-24 | St. Jude Children's Research Hospital | Expression of factor ix in gene therapy vectors |
| WO2016161446A1 (en) * | 2015-04-03 | 2016-10-06 | Dana-Farber Cancer Institute, Inc. | Composition and methods of genome editing of b-cells |
| US20160376373A1 (en) * | 2015-06-24 | 2016-12-29 | Janssen Biotech, Inc. | Immune Modulation and Treatment of Solid Tumors with Antibodies that Specifically Bind CD38 |
| US20170016027A1 (en) * | 2015-07-13 | 2017-01-19 | Sangamo Biosciences, Inc. | Delivery methods and compositions for nuclease-mediated genome engineering |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2003901511A0 (en) * | 2003-03-28 | 2003-04-17 | Bionomics Limited | Nucleic acid molecules associated with angiogenesis II |
| US9834787B2 (en) * | 2009-04-09 | 2017-12-05 | Sangamo Therapeutics, Inc. | Targeted integration into stem cells |
| AU2014265331B2 (en) * | 2013-05-15 | 2019-12-05 | Sangamo Therapeutics, Inc. | Methods and compositions for treatment of a genetic condition |
| US9757420B2 (en) * | 2014-07-25 | 2017-09-12 | Sangamo Therapeutics, Inc. | Gene editing for HIV gene therapy |
| CN106795488B (zh) * | 2014-09-16 | 2021-03-30 | 桑格摩治疗股份有限公司 | 用于造血干细胞中核酸酶介导的基因组工程化和校正的方法和组合物 |
| EP4177336A1 (en) * | 2014-12-19 | 2023-05-10 | Immusoft Corporation | B cells for in vivo delivery of therapeutic agents |
| EP3402533B1 (en) * | 2016-01-15 | 2021-08-04 | Sangamo Therapeutics, Inc. | Methods and compositions for the treatment of neurologic disease |
| EP3573464A4 (en) * | 2017-01-26 | 2020-12-30 | Sangamo Therapeutics, Inc. | B CELL ENGINEERING |
| CN111533799A (zh) * | 2017-04-10 | 2020-08-14 | 伊玛提克斯生物技术有限公司 | 用于白血病和其他癌症免疫治疗的肽和肽组合物 |
| WO2018232296A1 (en) * | 2017-06-16 | 2018-12-20 | Sangamo Therapeutics, Inc. | Targeted disruption of t cell and/or hla receptors |
| MX2020001594A (es) * | 2017-08-08 | 2020-12-09 | Sangamo Therapeutics Inc | Direccionamiento celular mediado por receptor de antigeno quimerico. |
| CN111565730B (zh) * | 2017-11-09 | 2024-09-17 | 桑格摩生物治疗股份有限公司 | 细胞因子诱导型含sh2蛋白（cish）基因的遗传修饰 |
| US20230158070A1 (en) * | 2018-01-30 | 2023-05-25 | Cellectis | Combination comprising allogeneic immune cells deficient for an antigen present on both t-cells and pathological cells and therapeutic antibody against said antigen |
| AU2019327913A1 (en) * | 2018-08-29 | 2021-03-18 | Nanjing Legend Biotech Co., Ltd. | Anti-mesothelin chimeric antigen receptor (CAR) constructs and uses thereof |
| CN113748126A (zh) * | 2018-11-30 | 2021-12-03 | 因提玛生物科学公司 | 鉴定免疫调节基因的方法 |
-
2018
- 2018-01-25 EP EP18744407.0A patent/EP3573464A4/en active Pending
- 2018-01-25 CA CA3051113A patent/CA3051113A1/en active Pending
- 2018-01-25 US US16/480,939 patent/US20190352614A1/en not_active Abandoned
- 2018-01-25 MX MX2019008844A patent/MX2019008844A/es unknown
- 2018-01-25 JP JP2019540095A patent/JP2020505044A/ja not_active Withdrawn
- 2018-01-25 KR KR1020197023790A patent/KR20190111063A/ko not_active Ceased
- 2018-01-25 AU AU2018212652A patent/AU2018212652B2/en not_active Ceased
- 2018-01-25 IL IL268110A patent/IL268110B2/en unknown
- 2018-01-25 WO PCT/US2018/015180 patent/WO2018140573A1/en not_active Ceased
- 2018-01-25 CN CN201880021264.1A patent/CN110536963A/zh active Pending
- 2018-01-25 BR BR112019015355A patent/BR112019015355A2/pt not_active IP Right Cessation
-
2022
- 2022-10-28 JP JP2022173206A patent/JP2022191524A/ja active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20110287532A1 (en) * | 2004-09-22 | 2011-11-24 | St. Jude Children's Research Hospital | Expression of factor ix in gene therapy vectors |
| WO2016161446A1 (en) * | 2015-04-03 | 2016-10-06 | Dana-Farber Cancer Institute, Inc. | Composition and methods of genome editing of b-cells |
| US20160376373A1 (en) * | 2015-06-24 | 2016-12-29 | Janssen Biotech, Inc. | Immune Modulation and Treatment of Solid Tumors with Antibodies that Specifically Bind CD38 |
| US20170016027A1 (en) * | 2015-07-13 | 2017-01-19 | Sangamo Biosciences, Inc. | Delivery methods and compositions for nuclease-mediated genome engineering |
Also Published As
| Publication number | Publication date |
|---|---|
| US20190352614A1 (en) | 2019-11-21 |
| JP2020505044A (ja) | 2020-02-20 |
| IL268110B1 (en) | 2023-09-01 |
| KR20190111063A (ko) | 2019-10-01 |
| EP3573464A4 (en) | 2020-12-30 |
| JP2022191524A (ja) | 2022-12-27 |
| WO2018140573A1 (en) | 2018-08-02 |
| AU2018212652B2 (en) | 2024-03-28 |
| CA3051113A1 (en) | 2018-08-02 |
| EP3573464A1 (en) | 2019-12-04 |
| RU2019126606A3 (enExample) | 2021-06-11 |
| IL268110A (en) | 2019-09-26 |
| BR112019015355A2 (pt) | 2020-05-19 |
| AU2018212652A1 (en) | 2019-08-01 |
| CN110536963A (zh) | 2019-12-03 |
| MX2019008844A (es) | 2019-09-10 |
| RU2019126606A (ru) | 2021-02-26 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2018212652B2 (en) | B-cell engineering | |
| JP7324249B2 (ja) | 肝臓特異的コンストラクト、第ｖｉｉｉ因子発現カセット、およびその使用の方法 | |
| US11634463B2 (en) | Methods and compositions for treating hemophilia | |
| EP3058072B1 (en) | Delivery methods and compositions for nuclease-mediated genome engineering | |
| EP3322297B1 (en) | Delivery methods and compositions for nuclease-mediated genome engineering | |
| RU2783116C2 (ru) | Модификация b-клеток | |
| RU2774874C2 (ru) | Печень-специфичные конструкции, экспрессионные кассеты фактора viii и способы их применения | |
| HK1226756B (zh) | 用於治疗血友病的方法和组合物 |