CN109843303A - 基因组编辑的原发b细胞及其制备和使用方法 - Google Patents
基因组编辑的原发b细胞及其制备和使用方法 Download PDFInfo
- Publication number
- CN109843303A CN109843303A CN201780059655.8A CN201780059655A CN109843303A CN 109843303 A CN109843303 A CN 109843303A CN 201780059655 A CN201780059655 A CN 201780059655A CN 109843303 A CN109843303 A CN 109843303A
- Authority
- CN
- China
- Prior art keywords
- cell
- primary
- genome
- nucleic acid
- gene
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 210000003719 b-lymphocyte Anatomy 0.000 title claims abstract description 323
- 238000002360 preparation method Methods 0.000 title description 5
- 238000000034 method Methods 0.000 claims abstract description 115
- 230000001225 therapeutic effect Effects 0.000 claims abstract description 58
- 210000004027 cell Anatomy 0.000 claims description 183
- 108090000623 proteins and genes Proteins 0.000 claims description 104
- 108091008875 B cell receptors Proteins 0.000 claims description 96
- 102000039446 nucleic acids Human genes 0.000 claims description 96
- 108020004707 nucleic acids Proteins 0.000 claims description 96
- 150000007523 nucleic acids Chemical class 0.000 claims description 96
- 230000014509 gene expression Effects 0.000 claims description 45
- 102100024222 B-lymphocyte antigen CD19 Human genes 0.000 claims description 41
- 101000980825 Homo sapiens B-lymphocyte antigen CD19 Proteins 0.000 claims description 41
- 230000004048 modification Effects 0.000 claims description 33
- 238000012986 modification Methods 0.000 claims description 33
- 102000004190 Enzymes Human genes 0.000 claims description 27
- 108090000790 Enzymes Proteins 0.000 claims description 27
- 239000000427 antigen Substances 0.000 claims description 26
- 108091007433 antigens Proteins 0.000 claims description 26
- 102000036639 antigens Human genes 0.000 claims description 26
- 238000013518 transcription Methods 0.000 claims description 21
- 230000035897 transcription Effects 0.000 claims description 21
- 206010028980 Neoplasm Diseases 0.000 claims description 20
- 201000010099 disease Diseases 0.000 claims description 20
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 20
- 230000004913 activation Effects 0.000 claims description 19
- 102000004169 proteins and genes Human genes 0.000 claims description 16
- 230000000694 effects Effects 0.000 claims description 15
- 230000000638 stimulation Effects 0.000 claims description 15
- 101710163270 Nuclease Proteins 0.000 claims description 12
- 201000011510 cancer Diseases 0.000 claims description 12
- 102100031658 C-X-C chemokine receptor type 5 Human genes 0.000 claims description 9
- 102100027207 CD27 antigen Human genes 0.000 claims description 9
- 101000922405 Homo sapiens C-X-C chemokine receptor type 5 Proteins 0.000 claims description 9
- 101000914511 Homo sapiens CD27 antigen Proteins 0.000 claims description 9
- 101100127690 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) FAA2 gene Proteins 0.000 claims description 9
- 230000008685 targeting Effects 0.000 claims description 9
- 102100032768 Complement receptor type 2 Human genes 0.000 claims description 8
- 101000941929 Homo sapiens Complement receptor type 2 Proteins 0.000 claims description 8
- 230000035772 mutation Effects 0.000 claims description 6
- 210000005259 peripheral blood Anatomy 0.000 claims description 6
- 239000011886 peripheral blood Substances 0.000 claims description 6
- 206010003445 Ascites Diseases 0.000 claims description 5
- 210000004962 mammalian cell Anatomy 0.000 claims description 5
- 239000000203 mixture Substances 0.000 claims description 5
- 230000002062 proliferating effect Effects 0.000 claims description 5
- 210000003954 umbilical cord Anatomy 0.000 claims description 4
- 230000009385 viral infection Effects 0.000 claims description 4
- 230000002255 enzymatic effect Effects 0.000 claims description 3
- 208000015181 infectious disease Diseases 0.000 claims description 3
- 230000001717 pathogenic effect Effects 0.000 claims description 3
- 230000002950 deficient Effects 0.000 claims description 2
- 230000035755 proliferation Effects 0.000 claims 2
- 208000006994 Precancerous Conditions Diseases 0.000 claims 1
- 208000036142 Viral infection Diseases 0.000 claims 1
- 230000003247 decreasing effect Effects 0.000 claims 1
- 230000005764 inhibitory process Effects 0.000 claims 1
- 244000052769 pathogen Species 0.000 claims 1
- 108020005004 Guide RNA Proteins 0.000 description 75
- 108020004414 DNA Proteins 0.000 description 62
- 238000004520 electroporation Methods 0.000 description 35
- 108091033409 CRISPR Proteins 0.000 description 34
- 241000700605 Viruses Species 0.000 description 34
- 238000001890 transfection Methods 0.000 description 27
- 108020004999 messenger RNA Proteins 0.000 description 21
- 102100035028 Alpha-L-iduronidase Human genes 0.000 description 18
- 101001019502 Homo sapiens Alpha-L-iduronidase Proteins 0.000 description 18
- 230000003321 amplification Effects 0.000 description 16
- 238000003199 nucleic acid amplification method Methods 0.000 description 16
- 239000013612 plasmid Substances 0.000 description 16
- 239000001963 growth medium Substances 0.000 description 15
- 239000007788 liquid Substances 0.000 description 15
- 229910052754 neon Inorganic materials 0.000 description 14
- GKAOGPIIYCISHV-UHFFFAOYSA-N neon atom Chemical compound [Ne] GKAOGPIIYCISHV-UHFFFAOYSA-N 0.000 description 14
- 238000005516 engineering process Methods 0.000 description 13
- 230000006801 homologous recombination Effects 0.000 description 13
- 238000002744 homologous recombination Methods 0.000 description 13
- 108010004729 Phycoerythrin Proteins 0.000 description 12
- 239000002585 base Substances 0.000 description 12
- 238000007385 chemical modification Methods 0.000 description 12
- 108090000765 processed proteins & peptides Proteins 0.000 description 11
- 238000012360 testing method Methods 0.000 description 10
- 238000010354 CRISPR gene editing Methods 0.000 description 9
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 8
- 239000000872 buffer Substances 0.000 description 8
- 239000000975 dye Substances 0.000 description 8
- 230000004083 survival effect Effects 0.000 description 8
- 108010029697 CD40 Ligand Proteins 0.000 description 7
- 102100032937 CD40 ligand Human genes 0.000 description 7
- 101800001494 Protease 2A Proteins 0.000 description 7
- 101800001066 Protein 2A Proteins 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 7
- 238000009795 derivation Methods 0.000 description 7
- 230000005782 double-strand break Effects 0.000 description 7
- 238000000684 flow cytometry Methods 0.000 description 7
- 238000002955 isolation Methods 0.000 description 7
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 7
- 102000005962 receptors Human genes 0.000 description 7
- 108020003175 receptors Proteins 0.000 description 7
- 210000000130 stem cell Anatomy 0.000 description 7
- 230000004936 stimulating effect Effects 0.000 description 7
- 102100021631 B-cell lymphoma 6 protein Human genes 0.000 description 6
- 101000971234 Homo sapiens B-cell lymphoma 6 protein Proteins 0.000 description 6
- 102000004388 Interleukin-4 Human genes 0.000 description 6
- 108090000978 Interleukin-4 Proteins 0.000 description 6
- 108020004684 Internal Ribosome Entry Sites Proteins 0.000 description 6
- 108091092724 Noncoding DNA Proteins 0.000 description 6
- 108010009975 Positive Regulatory Domain I-Binding Factor 1 Proteins 0.000 description 6
- 238000013459 approach Methods 0.000 description 6
- 230000001684 chronic effect Effects 0.000 description 6
- -1 idose glycosides Chemical class 0.000 description 6
- 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 6
- 238000013519 translation Methods 0.000 description 6
- 102100021569 Apoptosis regulator Bcl-2 Human genes 0.000 description 5
- 241000283923 Marmota monax Species 0.000 description 5
- 102100024894 PR domain zinc finger protein 1 Human genes 0.000 description 5
- 108091093126 WHP Posttrascriptional Response Element Proteins 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- 210000001728 clone cell Anatomy 0.000 description 5
- 208000006454 hepatitis Diseases 0.000 description 5
- 231100000283 hepatitis Toxicity 0.000 description 5
- 238000005259 measurement Methods 0.000 description 5
- 238000009126 molecular therapy Methods 0.000 description 5
- 230000035899 viability Effects 0.000 description 5
- 238000010356 CRISPR-Cas9 genome editing Methods 0.000 description 4
- 208000024720 Fabry Disease Diseases 0.000 description 4
- 208000015872 Gaucher disease Diseases 0.000 description 4
- 208000032007 Glycogen storage disease due to acid maltase deficiency Diseases 0.000 description 4
- 206010053185 Glycogen storage disease type II Diseases 0.000 description 4
- 239000012124 Opti-MEM Substances 0.000 description 4
- 241001648840 Thosea asigna virus Species 0.000 description 4
- 230000033228 biological regulation Effects 0.000 description 4
- 230000008859 change Effects 0.000 description 4
- 238000010586 diagram Methods 0.000 description 4
- 210000002472 endoplasmic reticulum Anatomy 0.000 description 4
- 239000013613 expression plasmid Substances 0.000 description 4
- 238000001476 gene delivery Methods 0.000 description 4
- 201000004502 glycogen storage disease II Diseases 0.000 description 4
- 229930182470 glycoside Natural products 0.000 description 4
- 108091008042 inhibitory receptors Proteins 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 238000003780 insertion Methods 0.000 description 4
- 230000037431 insertion Effects 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 210000001806 memory b lymphocyte Anatomy 0.000 description 4
- 208000022018 mucopolysaccharidosis type 2 Diseases 0.000 description 4
- 230000006780 non-homologous end joining Effects 0.000 description 4
- 239000002773 nucleotide Substances 0.000 description 4
- 125000003729 nucleotide group Chemical group 0.000 description 4
- 210000003705 ribosome Anatomy 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- 239000012096 transfection reagent Substances 0.000 description 4
- 230000003612 virological effect Effects 0.000 description 4
- 241000324499 Alkalibacillus Species 0.000 description 3
- 241000702421 Dependoparvovirus Species 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 101000971171 Homo sapiens Apoptosis regulator Bcl-2 Proteins 0.000 description 3
- 241000713666 Lentivirus Species 0.000 description 3
- 101100508818 Mus musculus Inpp5k gene Proteins 0.000 description 3
- 108091034117 Oligonucleotide Proteins 0.000 description 3
- 101100366438 Rattus norvegicus Sphkap gene Proteins 0.000 description 3
- 108091028113 Trans-activating crRNA Proteins 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 230000001154 acute effect Effects 0.000 description 3
- 230000009824 affinity maturation Effects 0.000 description 3
- 230000002155 anti-virotic effect Effects 0.000 description 3
- 239000003443 antiviral agent Substances 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 238000004113 cell culture Methods 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 238000004132 cross linking Methods 0.000 description 3
- 238000012217 deletion Methods 0.000 description 3
- 230000037430 deletion Effects 0.000 description 3
- 238000013461 design Methods 0.000 description 3
- 239000003623 enhancer Substances 0.000 description 3
- 150000002168 ethanoic acid esters Chemical class 0.000 description 3
- 238000012239 gene modification Methods 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- 230000010354 integration Effects 0.000 description 3
- 230000003834 intracellular effect Effects 0.000 description 3
- 230000035800 maturation Effects 0.000 description 3
- 238000006384 oligomerization reaction Methods 0.000 description 3
- 238000005457 optimization Methods 0.000 description 3
- 229940127084 other anti-cancer agent Drugs 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 3
- 238000012546 transfer Methods 0.000 description 3
- 238000011282 treatment Methods 0.000 description 3
- 208000031261 Acute myeloid leukaemia Diseases 0.000 description 2
- 102100025218 B-cell differentiation antigen CD72 Human genes 0.000 description 2
- 102100038080 B-cell receptor CD22 Human genes 0.000 description 2
- 108091012583 BCL2 Proteins 0.000 description 2
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 2
- 102000051485 Bcl-2 family Human genes 0.000 description 2
- 108700038897 Bcl-2 family Proteins 0.000 description 2
- 101150013553 CD40 gene Proteins 0.000 description 2
- 102100024533 Carcinoembryonic antigen-related cell adhesion molecule 1 Human genes 0.000 description 2
- 108010019670 Chimeric Antigen Receptors Proteins 0.000 description 2
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 2
- 108020004705 Codon Proteins 0.000 description 2
- 206010010099 Combined immunodeficiency Diseases 0.000 description 2
- 102100023583 Cyclic AMP-dependent transcription factor ATF-6 alpha Human genes 0.000 description 2
- 102100030801 Elongation factor 1-alpha 1 Human genes 0.000 description 2
- 102100027723 Endogenous retrovirus group K member 6 Rec protein Human genes 0.000 description 2
- 101710091045 Envelope protein Proteins 0.000 description 2
- 102100034174 Eukaryotic translation initiation factor 2-alpha kinase 3 Human genes 0.000 description 2
- 241000710198 Foot-and-mouth disease virus Species 0.000 description 2
- 108090000288 Glycoproteins Proteins 0.000 description 2
- 102000003886 Glycoproteins Human genes 0.000 description 2
- 229920002683 Glycosaminoglycan Polymers 0.000 description 2
- 102100031573 Hematopoietic progenitor cell antigen CD34 Human genes 0.000 description 2
- 208000017604 Hodgkin disease Diseases 0.000 description 2
- 101000934359 Homo sapiens B-cell differentiation antigen CD72 Proteins 0.000 description 2
- 101000884305 Homo sapiens B-cell receptor CD22 Proteins 0.000 description 2
- 101100383038 Homo sapiens CD19 gene Proteins 0.000 description 2
- 101000981093 Homo sapiens Carcinoembryonic antigen-related cell adhesion molecule 1 Proteins 0.000 description 2
- 101000911390 Homo sapiens Coagulation factor VIII Proteins 0.000 description 2
- 101000905751 Homo sapiens Cyclic AMP-dependent transcription factor ATF-6 alpha Proteins 0.000 description 2
- 101000920078 Homo sapiens Elongation factor 1-alpha 1 Proteins 0.000 description 2
- 101000777663 Homo sapiens Hematopoietic progenitor cell antigen CD34 Proteins 0.000 description 2
- 101001138062 Homo sapiens Leukocyte-associated immunoglobulin-like receptor 1 Proteins 0.000 description 2
- 101000934341 Homo sapiens T-cell surface glycoprotein CD5 Proteins 0.000 description 2
- 241000701085 Human alphaherpesvirus 3 Species 0.000 description 2
- 241000725303 Human immunodeficiency virus Species 0.000 description 2
- 102000004157 Hydrolases Human genes 0.000 description 2
- 108090000604 Hydrolases Proteins 0.000 description 2
- 108010017736 Leukocyte Immunoglobulin-like Receptor B1 Proteins 0.000 description 2
- 102100025584 Leukocyte immunoglobulin-like receptor subfamily B member 1 Human genes 0.000 description 2
- 102100020943 Leukocyte-associated immunoglobulin-like receptor 1 Human genes 0.000 description 2
- 102100033448 Lysosomal alpha-glucosidase Human genes 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 201000003793 Myelodysplastic syndrome Diseases 0.000 description 2
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 2
- 238000012408 PCR amplification Methods 0.000 description 2
- 108091008010 PERKs Proteins 0.000 description 2
- 102100040678 Programmed cell death protein 1 Human genes 0.000 description 2
- 101710188315 Protein X Proteins 0.000 description 2
- 241000700584 Simplexvirus Species 0.000 description 2
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 2
- 102100025244 T-cell surface glycoprotein CD5 Human genes 0.000 description 2
- 210000001744 T-lymphocyte Anatomy 0.000 description 2
- 102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 description 2
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 201000009628 adenosine deaminase deficiency Diseases 0.000 description 2
- 238000012197 amplification kit Methods 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 238000004873 anchoring Methods 0.000 description 2
- 208000036556 autosomal recessive T cell-negative B cell-negative NK cell-negative due to adenosine deaminase deficiency severe combined immunodeficiency Diseases 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 238000002659 cell therapy Methods 0.000 description 2
- 230000003833 cell viability Effects 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 230000004186 co-expression Effects 0.000 description 2
- 230000029087 digestion Effects 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000004043 dyeing Methods 0.000 description 2
- 108010048367 enhanced green fluorescent protein Proteins 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 238000001415 gene therapy Methods 0.000 description 2
- 238000010362 genome editing Methods 0.000 description 2
- 230000002394 glycogenic effect Effects 0.000 description 2
- 230000002607 hemopoietic effect Effects 0.000 description 2
- 102000057593 human F8 Human genes 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 230000002779 inactivation Effects 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 210000002751 lymph Anatomy 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- 208000030159 metabolic disease Diseases 0.000 description 2
- 108091070501 miRNA Proteins 0.000 description 2
- 201000002273 mucopolysaccharidosis II Diseases 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 238000007747 plating Methods 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 229940047431 recombinate Drugs 0.000 description 2
- 230000006798 recombination Effects 0.000 description 2
- 238000005215 recombination Methods 0.000 description 2
- 230000003252 repetitive effect Effects 0.000 description 2
- 230000000717 retained effect Effects 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 239000002002 slurry Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 230000009182 swimming Effects 0.000 description 2
- 238000010361 transduction Methods 0.000 description 2
- 230000026683 transduction Effects 0.000 description 2
- SWWQQSDRUYSMAR-UHFFFAOYSA-N 1-[(4-hydroxyphenyl)methyl]-1,2,3,4-tetrahydroisoquinoline-6,7-diol;hydrochloride Chemical group Cl.C1=CC(O)=CC=C1CC1C2=CC(O)=C(O)C=C2CCN1 SWWQQSDRUYSMAR-UHFFFAOYSA-N 0.000 description 1
- 102100031585 ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Human genes 0.000 description 1
- 108010005254 Activating Transcription Factors Proteins 0.000 description 1
- 102000005869 Activating Transcription Factors Human genes 0.000 description 1
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 1
- 241000702423 Adeno-associated virus - 2 Species 0.000 description 1
- 241000202702 Adeno-associated virus - 3 Species 0.000 description 1
- 241000580270 Adeno-associated virus - 4 Species 0.000 description 1
- 241001634120 Adeno-associated virus - 5 Species 0.000 description 1
- 241000972680 Adeno-associated virus - 6 Species 0.000 description 1
- 102000008682 Argonaute Proteins Human genes 0.000 description 1
- 108010088141 Argonaute Proteins Proteins 0.000 description 1
- 108700016171 Aspartate ammonia-lyases Proteins 0.000 description 1
- 102000019260 B-Cell Antigen Receptors Human genes 0.000 description 1
- 108010012919 B-Cell Antigen Receptors Proteins 0.000 description 1
- 230000003844 B-cell-activation Effects 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 208000003174 Brain Neoplasms Diseases 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 101150017501 CCR5 gene Proteins 0.000 description 1
- 101150018757 CD19 gene Proteins 0.000 description 1
- 102000000844 Cell Surface Receptors Human genes 0.000 description 1
- 108010001857 Cell Surface Receptors Proteins 0.000 description 1
- 108010051109 Cell-Penetrating Peptides Proteins 0.000 description 1
- 102000020313 Cell-Penetrating Peptides Human genes 0.000 description 1
- 206010010356 Congenital anomaly Diseases 0.000 description 1
- 230000007023 DNA restriction-modification system 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
- 208000001490 Dengue Diseases 0.000 description 1
- 206010012310 Dengue fever Diseases 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 102100030013 Endoribonuclease Human genes 0.000 description 1
- 101150066002 GFP gene Proteins 0.000 description 1
- 241000175212 Herpesvirales Species 0.000 description 1
- 208000010747 Hodgkins lymphoma Diseases 0.000 description 1
- 101000777636 Homo sapiens ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Proteins 0.000 description 1
- 101000834898 Homo sapiens Alpha-synuclein Proteins 0.000 description 1
- 101001010783 Homo sapiens Endoribonuclease Proteins 0.000 description 1
- 101000611936 Homo sapiens Programmed cell death protein 1 Proteins 0.000 description 1
- 101000652359 Homo sapiens Spermatogenesis-associated protein 2 Proteins 0.000 description 1
- 244000283207 Indigofera tinctoria Species 0.000 description 1
- 102100037850 Interferon gamma Human genes 0.000 description 1
- 108010074328 Interferon-gamma Proteins 0.000 description 1
- 102000003814 Interleukin-10 Human genes 0.000 description 1
- 108090000174 Interleukin-10 Proteins 0.000 description 1
- 102000003812 Interleukin-15 Human genes 0.000 description 1
- 108090000172 Interleukin-15 Proteins 0.000 description 1
- 108010002350 Interleukin-2 Proteins 0.000 description 1
- 102000000588 Interleukin-2 Human genes 0.000 description 1
- 102000004889 Interleukin-6 Human genes 0.000 description 1
- 108090001005 Interleukin-6 Proteins 0.000 description 1
- 102100021592 Interleukin-7 Human genes 0.000 description 1
- 108010002586 Interleukin-7 Proteins 0.000 description 1
- 208000007766 Kaposi sarcoma Diseases 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 241000713883 Myeloproliferative sarcoma virus Species 0.000 description 1
- 108091008877 NK cell receptors Proteins 0.000 description 1
- 241000204974 Natronobacterium Species 0.000 description 1
- 102000010648 Natural Killer Cell Receptors Human genes 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
- 241001672814 Porcine teschovirus 1 Species 0.000 description 1
- 101710089372 Programmed cell death protein 1 Proteins 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 238000011529 RT qPCR Methods 0.000 description 1
- 208000000453 Skin Neoplasms Diseases 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- 241001420369 Thosea Species 0.000 description 1
- 108700019146 Transgenes Proteins 0.000 description 1
- GLNADSQYFUSGOU-GPTZEZBUSA-J Trypan blue Chemical compound [Na+].[Na+].[Na+].[Na+].C1=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(/N=N/C3=CC=C(C=C3C)C=3C=C(C(=CC=3)\N=N\C=3C(=CC4=CC(=CC(N)=C4C=3O)S([O-])(=O)=O)S([O-])(=O)=O)C)=C(O)C2=C1N GLNADSQYFUSGOU-GPTZEZBUSA-J 0.000 description 1
- 208000002495 Uterine Neoplasms Diseases 0.000 description 1
- 241000710772 Yellow fever virus Species 0.000 description 1
- 241000907316 Zika virus Species 0.000 description 1
- 108010017070 Zinc Finger Nucleases Proteins 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 210000005006 adaptive immune system Anatomy 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 125000003275 alpha amino acid group Chemical group 0.000 description 1
- 238000000137 annealing Methods 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 230000005784 autoimmunity Effects 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000008499 blood brain barrier function Effects 0.000 description 1
- 210000001218 blood-brain barrier Anatomy 0.000 description 1
- 239000001045 blue dye Substances 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000020411 cell activation Effects 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 230000011748 cell maturation Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 235000013339 cereals Nutrition 0.000 description 1
- 208000019065 cervical carcinoma Diseases 0.000 description 1
- 239000005482 chemotactic factor Substances 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 238000011284 combination treatment Methods 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000006196 deacetylation Effects 0.000 description 1
- 238000003381 deacetylation reaction Methods 0.000 description 1
- 238000005034 decoration Methods 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 208000025729 dengue disease Diseases 0.000 description 1
- 238000001739 density measurement Methods 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 230000009025 developmental regulation Effects 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 230000005611 electricity Effects 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 239000012997 ficoll-paque Substances 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 231100000221 frame shift mutation induction Toxicity 0.000 description 1
- 230000037433 frameshift Effects 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 108010027225 gag-pol Fusion Proteins Proteins 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- 238000001502 gel electrophoresis Methods 0.000 description 1
- 238000003209 gene knockout Methods 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000000415 inactivating effect Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 230000002601 intratumoral effect Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 230000002101 lytic effect Effects 0.000 description 1
- 201000004792 malaria Diseases 0.000 description 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 238000000520 microinjection Methods 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 210000000822 natural killer cell Anatomy 0.000 description 1
- 238000013546 non-drug therapy Methods 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 210000003720 plasmablast Anatomy 0.000 description 1
- 230000008488 polyadenylation Effects 0.000 description 1
- 230000001124 posttranscriptional effect Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000020978 protein processing Effects 0.000 description 1
- 238000013139 quantization Methods 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 210000003370 receptor cell Anatomy 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 239000012744 reinforcing agent Substances 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 238000007480 sanger sequencing Methods 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 201000000849 skin cancer Diseases 0.000 description 1
- YEENEYXBHNNNGV-XEHWZWQGSA-M sodium;3-acetamido-5-[acetyl(methyl)amino]-2,4,6-triiodobenzoate;(2r,3r,4s,5s,6r)-2-[(2r,3s,4s,5r)-3,4-dihydroxy-2,5-bis(hydroxymethyl)oxolan-2-yl]oxy-6-(hydroxymethyl)oxane-3,4,5-triol Chemical compound [Na+].CC(=O)N(C)C1=C(I)C(NC(C)=O)=C(I)C(C([O-])=O)=C1I.O[C@H]1[C@H](O)[C@@H](CO)O[C@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 YEENEYXBHNNNGV-XEHWZWQGSA-M 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 201000011549 stomach cancer Diseases 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000003151 transfection method Methods 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 206010046766 uterine cancer Diseases 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 229940051021 yellow-fever virus Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
- C12N15/1138—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing against receptors or cell surface proteins
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
- C12N15/86—Viral vectors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
- A61K31/713—Double-stranded nucleic acids or oligonucleotides
-
- 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
- A61K40/24—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
-
- 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
- A61K40/42—Cancer antigens
-
- 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
- A61K40/46—Viral antigens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
-
- 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
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/16—Hydrolases (3) acting on ester bonds (3.1)
- C12N9/22—Ribonucleases [RNase]; Deoxyribonucleases [DNase]
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/10—Type of nucleic acid
- C12N2310/20—Type of nucleic acid involving clustered regularly interspaced short palindromic repeats [CRISPR]
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2501/00—Active agents used in cell culture processes, e.g. differentation
- C12N2501/20—Cytokines; Chemokines
- C12N2501/23—Interleukins [IL]
- C12N2501/2304—Interleukin-4 (IL-4)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2501/00—Active agents used in cell culture processes, e.g. differentation
- C12N2501/50—Cell markers; Cell surface determinants
- C12N2501/52—CD40, CD40-ligand (CD154)
-
- 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
- C12N2740/00—Reverse transcribing RNA viruses
- C12N2740/00011—Details
- C12N2740/10011—Retroviridae
- C12N2740/15011—Lentivirus, not HIV, e.g. FIV, SIV
- C12N2740/15041—Use of virus, viral particle or viral elements as a vector
- C12N2740/15043—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector
-
- 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
- C12N2740/00—Reverse transcribing RNA viruses
- C12N2740/00011—Details
- C12N2740/10011—Retroviridae
- C12N2740/16011—Human Immunodeficiency Virus, HIV
- C12N2740/16041—Use of virus, viral particle or viral elements as a vector
- C12N2740/16043—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector
-
- 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
- C12N2800/00—Nucleic acids vectors
- C12N2800/80—Vectors containing sites for inducing double-stranded breaks, e.g. meganuclease restriction sites
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Genetics & Genomics (AREA)
- Organic Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Biomedical Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Biotechnology (AREA)
- Epidemiology (AREA)
- General Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Medicinal Chemistry (AREA)
- Biochemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Microbiology (AREA)
- Immunology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Physics & Mathematics (AREA)
- Biophysics (AREA)
- Plant Pathology (AREA)
- Cell Biology (AREA)
- Hematology (AREA)
- Virology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Mycology (AREA)
- Diabetes (AREA)
- Endocrinology (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201662393512P | 2016-09-12 | 2016-09-12 | |
| US62/393,512 | 2016-09-12 | ||
| PCT/US2017/051182 WO2018049401A1 (en) | 2016-09-12 | 2017-09-12 | Genome edited primary b cell and methods of making and using |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN109843303A true CN109843303A (zh) | 2019-06-04 |
Family
ID=61562180
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201780059655.8A Pending CN109843303A (zh) | 2016-09-12 | 2017-09-12 | 基因组编辑的原发b细胞及其制备和使用方法 |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US20220168342A1 (enExample) |
| EP (1) | EP3509606A4 (enExample) |
| JP (2) | JP2019526270A (enExample) |
| CN (1) | CN109843303A (enExample) |
| AU (1) | AU2017322733B2 (enExample) |
| CA (1) | CA3036820A1 (enExample) |
| WO (1) | WO2018049401A1 (enExample) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA3056609A1 (en) | 2017-03-16 | 2018-09-20 | Seattle Children's Hospital (dba Seattle Children's Research Institute) | Engraftable cell-based immunotherapy for long-term delivery of therapeutic proteins |
| JP7698321B2 (ja) * | 2019-11-27 | 2025-06-25 | ボード オブ リージェンツ，ザ ユニバーシティ オブ テキサス システム | Ｂ細胞のｃａｒ形質導入とｃｒｉｓｐｒ遺伝子編集との大規模での組み合わせ |
| WO2023283585A2 (en) * | 2021-07-06 | 2023-01-12 | Vor Biopharma Inc. | Inhibitor oligonucleotides and methods of use thereof |
| US20240352420A1 (en) * | 2021-07-29 | 2024-10-24 | Regents Of The University Of Minnesota | Multiplex base editing of primary human natural killer cells |
| WO2024015925A2 (en) * | 2022-07-13 | 2024-01-18 | Vor Biopharma Inc. | Compositions and methods for artificial protospacer adjacent motif (pam) generation |
| WO2024196669A2 (en) * | 2023-03-17 | 2024-09-26 | Walking Fish Therapeutics, Inc. | Methods for in vivo editing of b cells |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2016100932A1 (en) * | 2014-12-19 | 2016-06-23 | Immusoft Corporation | B cells for in vivo delivery of therapeutic agents |
| CN109072193A (zh) * | 2015-04-03 | 2018-12-21 | 达纳-法伯癌症研究所有限公司 | B细胞基因组编辑的组合物和方法 |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2965224A1 (en) * | 2014-10-24 | 2016-04-28 | Bcrt Holding Bv | T cell-based immunotherapeutics |
-
2017
- 2017-09-12 WO PCT/US2017/051182 patent/WO2018049401A1/en not_active Ceased
- 2017-09-12 JP JP2019513999A patent/JP2019526270A/ja not_active Withdrawn
- 2017-09-12 AU AU2017322733A patent/AU2017322733B2/en active Active
- 2017-09-12 CA CA3036820A patent/CA3036820A1/en active Pending
- 2017-09-12 EP EP17849776.4A patent/EP3509606A4/en active Pending
- 2017-09-12 CN CN201780059655.8A patent/CN109843303A/zh active Pending
- 2017-09-12 US US16/332,555 patent/US20220168342A1/en active Pending
-
2022
- 2022-10-07 JP JP2022162584A patent/JP2022189863A/ja active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2016100932A1 (en) * | 2014-12-19 | 2016-06-23 | Immusoft Corporation | B cells for in vivo delivery of therapeutic agents |
| CN109072193A (zh) * | 2015-04-03 | 2018-12-21 | 达纳-法伯癌症研究所有限公司 | B细胞基因组编辑的组合物和方法 |
Non-Patent Citations (3)
| Title |
|---|
| TAEK-CHIN CHEONG ET AL: "Editing of mouse and human immunoglobulin genes by CRISPR-Cas9 system", 《NATURE COMMUNICATIONS》 * |
| 吴敏毓 等: "《医学免疫学》", 31 December 2002 * |
| 陈锋: "通过基因修饰的抗原特异性B淋巴细胞的体内扩增提高外源治疗基因的表达水平", 《中国优秀博硕士学位论文全文数据库（博士）医药卫生科技辑》 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CA3036820A1 (en) | 2018-03-15 |
| WO2018049401A8 (en) | 2019-04-04 |
| EP3509606A4 (en) | 2020-10-07 |
| AU2017322733A1 (en) | 2019-04-11 |
| EP3509606A1 (en) | 2019-07-17 |
| WO2018049401A1 (en) | 2018-03-15 |
| AU2017322733B2 (en) | 2024-05-09 |
| JP2019526270A (ja) | 2019-09-19 |
| JP2022189863A (ja) | 2022-12-22 |
| US20220168342A1 (en) | 2022-06-02 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2017322733B2 (en) | Genome edited primary B cell and methods of making and using | |
| AU2019315440B2 (en) | Improving the efficacy and safety of adoptive cellular therapies | |
| AU2018306307B2 (en) | Enhanced chimeric antigen receptors and use thereof | |
| AU2019204429B2 (en) | Modified hematopoietic stem/progenitor and non-T effector cells, and uses thereof | |
| US20220220188A1 (en) | Compositions and methods of chimeric alloantigen receptor t cells | |
| US20250236884A1 (en) | Modified adenoviruses | |
| TW202237826A (zh) | 基因編輯的自然殺手細胞 | |
| KR102696275B1 (ko) | 염증을 치료 및 예방하기 위한 조성물 및 방법 | |
| AU2017230011A1 (en) | Genome edited immune effector cells | |
| CA3036926A1 (en) | Modified stem cell memory t cells, methods of making and methods of using same | |
| CN110036112A (zh) | 引发受主要组织相容性复合体e分子限制的t细胞的巨细胞病毒载体 | |
| KR20240119152A (ko) | 재조합 glut1 아데노-관련 바이러스 벡터 작제물 및 glut1 발현을 회복하기 위한 관련된 방법 | |
| KR20200066289A (ko) | 인자 viii (fviii) 유전자 요법 방법 | |
| US20240050550A1 (en) | Infectious disease antigens and vaccines | |
| AU2018251150B2 (en) | New sequence specific reagents targeting CCR5 in primary hematopoietic cells | |
| US20230310563A1 (en) | Antigen-encoding cassettes | |
| CN112159809B (zh) | 靶向CTGF基因的gRNA及其应用 | |
| TW202227476A (zh) | 編碼GJB2之重組腺相關病毒(rAAV)及其用途 | |
| ES2693593T3 (es) | Composición y método para la diversificación de secuencias diana | |
| CN113072645B (zh) | 一种靶向EphA2抗原的癌症疫苗 | |
| AU2018326582B2 (en) | Retinal promoter and uses thereof | |
| KR20240004433A (ko) | Ert2 돌연변이체 및 이의 용도 | |
| CN116997657A (zh) | 编码GJB2的重组腺相关病毒(rAAV)及其用途 | |
| KR20240011184A (ko) | Ciita 표적화 아연 핑거 뉴클레아제 | |
| WO2024163805A1 (en) | Methods and compositions for genomic integration |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |