AU2021300358A1 - Methods and compositions for editing the B2M locus in B cells - Google Patents
Methods and compositions for editing the B2M locus in B cells Download PDFInfo
- Publication number
- AU2021300358A1 AU2021300358A1 AU2021300358A AU2021300358A AU2021300358A1 AU 2021300358 A1 AU2021300358 A1 AU 2021300358A1 AU 2021300358 A AU2021300358 A AU 2021300358A AU 2021300358 A AU2021300358 A AU 2021300358A AU 2021300358 A1 AU2021300358 A1 AU 2021300358A1
- Authority
- AU
- Australia
- Prior art keywords
- cell
- modified
- cells
- gene
- nuclease
- 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 284
- 238000000034 method Methods 0.000 title claims abstract description 118
- 239000000203 mixture Substances 0.000 title abstract description 28
- 210000004027 cell Anatomy 0.000 claims abstract description 265
- 102000015736 beta 2-Microglobulin Human genes 0.000 claims abstract description 212
- 108010081355 beta 2-Microglobulin Proteins 0.000 claims abstract description 212
- 101150076800 B2M gene Proteins 0.000 claims abstract description 124
- 210000002865 immune cell Anatomy 0.000 claims abstract description 71
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 58
- 230000000735 allogeneic effect Effects 0.000 claims abstract description 47
- 230000001965 increasing effect Effects 0.000 claims abstract description 35
- 230000002147 killing effect Effects 0.000 claims abstract description 30
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 110
- 101710163270 Nuclease Proteins 0.000 claims description 109
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 100
- 229920001184 polypeptide Polymers 0.000 claims description 98
- 210000001744 T-lymphocyte Anatomy 0.000 claims description 74
- 108020005004 Guide RNA Proteins 0.000 claims description 73
- 210000000822 natural killer cell Anatomy 0.000 claims description 59
- 102000039446 nucleic acids Human genes 0.000 claims description 52
- 108020004707 nucleic acids Proteins 0.000 claims description 52
- 150000007523 nucleic acids Chemical class 0.000 claims description 52
- 230000008439 repair process Effects 0.000 claims description 50
- 239000002299 complementary DNA Substances 0.000 claims description 37
- 102000004169 proteins and genes Human genes 0.000 claims description 34
- 239000002773 nucleotide Substances 0.000 claims description 33
- 125000003729 nucleotide group Chemical group 0.000 claims description 33
- 238000001727 in vivo Methods 0.000 claims description 31
- 230000001225 therapeutic effect Effects 0.000 claims description 30
- 238000010459 TALEN Methods 0.000 claims description 24
- 102100028970 HLA class I histocompatibility antigen, alpha chain E Human genes 0.000 claims description 22
- 239000013603 viral vector Substances 0.000 claims description 22
- 101000986085 Homo sapiens HLA class I histocompatibility antigen, alpha chain E Proteins 0.000 claims description 20
- 108010017070 Zinc Finger Nucleases Proteins 0.000 claims description 19
- 239000013598 vector Substances 0.000 claims description 18
- 108091033409 CRISPR Proteins 0.000 claims description 17
- 230000000295 complement effect Effects 0.000 claims description 17
- 230000001472 cytotoxic effect Effects 0.000 claims description 17
- 241000702421 Dependoparvovirus Species 0.000 claims description 16
- 231100000433 cytotoxic Toxicity 0.000 claims description 16
- 102000004127 Cytokines Human genes 0.000 claims description 10
- 108090000695 Cytokines Proteins 0.000 claims description 10
- 102000004190 Enzymes Human genes 0.000 claims description 10
- 108090000790 Enzymes Proteins 0.000 claims description 10
- 239000000427 antigen Substances 0.000 claims description 10
- 108091007433 antigens Proteins 0.000 claims description 10
- 102000036639 antigens Human genes 0.000 claims description 10
- 102100022641 Coagulation factor IX Human genes 0.000 claims description 9
- 108010042407 Endonucleases Proteins 0.000 claims description 9
- 108010076282 Factor IX Proteins 0.000 claims description 9
- 102100028967 HLA class I histocompatibility antigen, alpha chain G Human genes 0.000 claims description 9
- 108010024164 HLA-G Antigens Proteins 0.000 claims description 9
- 229960004222 factor ix Drugs 0.000 claims description 9
- 210000003958 hematopoietic stem cell Anatomy 0.000 claims description 9
- 102100035765 Angiotensin-converting enzyme 2 Human genes 0.000 claims description 8
- 108090000975 Angiotensin-converting enzyme 2 Proteins 0.000 claims description 8
- 102000004547 Glucosylceramidase Human genes 0.000 claims description 8
- 108010017544 Glucosylceramidase Proteins 0.000 claims description 8
- 102100033342 Lysosomal acid glucosylceramidase Human genes 0.000 claims description 8
- 102100024295 Maltase-glucoamylase Human genes 0.000 claims description 8
- 101150054399 ace2 gene Proteins 0.000 claims description 8
- 239000002253 acid Substances 0.000 claims description 8
- 102000005840 alpha-Galactosidase Human genes 0.000 claims description 8
- 108010030291 alpha-Galactosidase Proteins 0.000 claims description 8
- 108010028144 alpha-Glucosidases Proteins 0.000 claims description 8
- 230000027455 binding Effects 0.000 claims description 8
- 102100039341 Atrial natriuretic peptide receptor 2 Human genes 0.000 claims description 7
- 101710102159 Atrial natriuretic peptide receptor 2 Proteins 0.000 claims description 7
- 108010019670 Chimeric Antigen Receptors Proteins 0.000 claims description 7
- 210000004667 early pro-b cell Anatomy 0.000 claims description 7
- 239000012634 fragment Substances 0.000 claims description 7
- 210000003297 immature b lymphocyte Anatomy 0.000 claims description 7
- 210000000014 large pre-b cell Anatomy 0.000 claims description 7
- 210000002202 late pro-b cell Anatomy 0.000 claims description 7
- 210000002809 long lived plasma cell Anatomy 0.000 claims description 7
- 210000003826 marginal zone b cell Anatomy 0.000 claims description 7
- 210000003519 mature b lymphocyte Anatomy 0.000 claims description 7
- 210000001806 memory b lymphocyte Anatomy 0.000 claims description 7
- 210000003720 plasmablast Anatomy 0.000 claims description 7
- 108020003175 receptors Proteins 0.000 claims description 7
- 102000005962 receptors Human genes 0.000 claims description 7
- 210000000345 small pre-b cell Anatomy 0.000 claims description 7
- 102100028966 HLA class I histocompatibility antigen, alpha chain F Human genes 0.000 claims description 6
- 101000986080 Homo sapiens HLA class I histocompatibility antigen, alpha chain F Proteins 0.000 claims description 6
- 238000001802 infusion Methods 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 101100508818 Mus musculus Inpp5k gene Proteins 0.000 claims description 3
- 101100366438 Rattus norvegicus Sphkap gene Proteins 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 102000004533 Endonucleases Human genes 0.000 claims 1
- 108020001507 fusion proteins Proteins 0.000 description 52
- 102000037865 fusion proteins Human genes 0.000 description 52
- 102000040430 polynucleotide Human genes 0.000 description 48
- 108091033319 polynucleotide Proteins 0.000 description 48
- 239000002157 polynucleotide Substances 0.000 description 48
- 238000010362 genome editing Methods 0.000 description 33
- 230000000415 inactivating effect Effects 0.000 description 32
- 210000004180 plasmocyte Anatomy 0.000 description 16
- 108020004414 DNA Proteins 0.000 description 15
- 239000013638 trimer Substances 0.000 description 14
- 102000004389 Ribonucleoproteins Human genes 0.000 description 13
- 108010081734 Ribonucleoproteins Proteins 0.000 description 13
- 238000012546 transfer Methods 0.000 description 13
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 12
- 238000002744 homologous recombination Methods 0.000 description 12
- 230000006801 homologous recombination Effects 0.000 description 12
- 238000003780 insertion Methods 0.000 description 11
- 230000037431 insertion Effects 0.000 description 11
- 238000011740 C57BL/6 mouse Methods 0.000 description 10
- 241001529936 Murinae Species 0.000 description 10
- 230000022534 cell killing Effects 0.000 description 10
- 101000868279 Homo sapiens Leukocyte surface antigen CD47 Proteins 0.000 description 9
- 101000884271 Homo sapiens Signal transducer CD24 Proteins 0.000 description 9
- 102100032913 Leukocyte surface antigen CD47 Human genes 0.000 description 9
- 102100038081 Signal transducer CD24 Human genes 0.000 description 9
- 238000003556 assay Methods 0.000 description 9
- 238000012986 modification Methods 0.000 description 9
- 102100031780 Endonuclease Human genes 0.000 description 8
- 108700018351 Major Histocompatibility Complex Proteins 0.000 description 8
- 238000003501 co-culture Methods 0.000 description 8
- 238000012217 deletion Methods 0.000 description 8
- 230000037430 deletion Effects 0.000 description 8
- 230000004048 modification Effects 0.000 description 8
- 230000020382 suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I Effects 0.000 description 8
- 210000001266 CD8-positive T-lymphocyte Anatomy 0.000 description 7
- 238000002474 experimental method Methods 0.000 description 7
- 230000001404 mediated effect Effects 0.000 description 7
- 238000006467 substitution reaction Methods 0.000 description 7
- 208000002267 Anti-neutrophil cytoplasmic antibody-associated vasculitis Diseases 0.000 description 6
- 238000010453 CRISPR/Cas method Methods 0.000 description 6
- 101000937544 Homo sapiens Beta-2-microglobulin Proteins 0.000 description 6
- 102100030704 Interleukin-21 Human genes 0.000 description 6
- 238000005206 flow analysis Methods 0.000 description 6
- 102000047279 human B2M Human genes 0.000 description 6
- 230000002779 inactivation Effects 0.000 description 6
- 108010074108 interleukin-21 Proteins 0.000 description 6
- 230000004083 survival effect Effects 0.000 description 6
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 5
- 239000013607 AAV vector Substances 0.000 description 5
- 108700028369 Alleles Proteins 0.000 description 5
- 108091026890 Coding region Proteins 0.000 description 5
- 102000008949 Histocompatibility Antigens Class I Human genes 0.000 description 5
- 108010088652 Histocompatibility Antigens Class I Proteins 0.000 description 5
- 241000699670 Mus sp. Species 0.000 description 5
- 108091028043 Nucleic acid sequence Proteins 0.000 description 5
- 230000034431 double-strand break repair via homologous recombination Effects 0.000 description 5
- 230000002068 genetic effect Effects 0.000 description 5
- 238000000338 in vitro Methods 0.000 description 5
- 239000002243 precursor Substances 0.000 description 5
- 102000053602 DNA Human genes 0.000 description 4
- 102100028976 HLA class I histocompatibility antigen, B alpha chain Human genes 0.000 description 4
- 108010058607 HLA-B Antigens Proteins 0.000 description 4
- 101000874179 Homo sapiens Syndecan-1 Proteins 0.000 description 4
- 241000699666 Mus <mouse, genus> Species 0.000 description 4
- 102100035721 Syndecan-1 Human genes 0.000 description 4
- 108010073062 Transcription Activator-Like Effectors Proteins 0.000 description 4
- 206010052779 Transplant rejections Diseases 0.000 description 4
- 238000000684 flow cytometry Methods 0.000 description 4
- 229920002521 macromolecule Polymers 0.000 description 4
- 230000006780 non-homologous end joining Effects 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 3
- 108090001005 Interleukin-6 Proteins 0.000 description 3
- 101100219625 Mus musculus Casd1 gene Proteins 0.000 description 3
- 108091008874 T cell receptors Proteins 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 101150055766 cat gene Proteins 0.000 description 3
- 230000004069 differentiation Effects 0.000 description 3
- 230000005782 double-strand break Effects 0.000 description 3
- 230000037451 immune surveillance Effects 0.000 description 3
- 230000001939 inductive effect Effects 0.000 description 3
- 230000010354 integration Effects 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000003550 marker Substances 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 108091008146 restriction endonucleases Proteins 0.000 description 3
- 230000008685 targeting Effects 0.000 description 3
- 238000010361 transduction Methods 0.000 description 3
- 230000026683 transduction Effects 0.000 description 3
- 238000001890 transfection Methods 0.000 description 3
- 230000003612 virological effect Effects 0.000 description 3
- 102100024222 B-lymphocyte antigen CD19 Human genes 0.000 description 2
- 238000011725 BALB/c mouse Methods 0.000 description 2
- 108020004705 Codon Proteins 0.000 description 2
- 230000007018 DNA scission Effects 0.000 description 2
- 230000004568 DNA-binding Effects 0.000 description 2
- 102100028972 HLA class I histocompatibility antigen, A alpha chain Human genes 0.000 description 2
- 108010075704 HLA-A Antigens Proteins 0.000 description 2
- 101000980825 Homo sapiens B-lymphocyte antigen CD19 Proteins 0.000 description 2
- 101100220044 Homo sapiens CD34 gene Proteins 0.000 description 2
- 101100395313 Homo sapiens HLA-E gene Proteins 0.000 description 2
- -1 IGMC Proteins 0.000 description 2
- 108010002350 Interleukin-2 Proteins 0.000 description 2
- 102000018697 Membrane Proteins Human genes 0.000 description 2
- 108010052285 Membrane Proteins Proteins 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 108020004682 Single-Stranded DNA Proteins 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 238000011316 allogeneic transplantation Methods 0.000 description 2
- 239000011324 bead Substances 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 230000001351 cycling effect Effects 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 230000003828 downregulation Effects 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 230000008030 elimination Effects 0.000 description 2
- 238000003379 elimination reaction Methods 0.000 description 2
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 2
- 230000037433 frameshift Effects 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 230000004927 fusion Effects 0.000 description 2
- 102000054766 genetic haplotypes Human genes 0.000 description 2
- 210000005260 human cell Anatomy 0.000 description 2
- 230000028993 immune response Effects 0.000 description 2
- 230000016784 immunoglobulin production Effects 0.000 description 2
- 108020004999 messenger RNA Proteins 0.000 description 2
- 244000052769 pathogen Species 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 239000011701 zinc Substances 0.000 description 2
- 229910052725 zinc Inorganic materials 0.000 description 2
- 241000702423 Adeno-associated virus - 2 Species 0.000 description 1
- 102100021253 Antileukoproteinase Human genes 0.000 description 1
- 108091008875 B cell receptors Proteins 0.000 description 1
- 102100035875 C-C chemokine receptor type 5 Human genes 0.000 description 1
- 101710149870 C-C chemokine receptor type 5 Proteins 0.000 description 1
- 108010029697 CD40 Ligand Proteins 0.000 description 1
- 102100032937 CD40 ligand Human genes 0.000 description 1
- 238000010356 CRISPR-Cas9 genome editing Methods 0.000 description 1
- 102100024965 Caspase recruitment domain-containing protein 11 Human genes 0.000 description 1
- 230000033616 DNA repair Effects 0.000 description 1
- 102100030442 Derlin-3 Human genes 0.000 description 1
- 102100021807 ER degradation-enhancing alpha-mannosidase-like protein 1 Human genes 0.000 description 1
- 108010037179 Endodeoxyribonucleases Proteins 0.000 description 1
- 102000011750 Endodeoxyribonucleases Human genes 0.000 description 1
- 108700024394 Exon Proteins 0.000 description 1
- 108010054218 Factor VIII Proteins 0.000 description 1
- 102000001690 Factor VIII Human genes 0.000 description 1
- 102100028971 HLA class I histocompatibility antigen, C alpha chain Human genes 0.000 description 1
- 108010052199 HLA-C Antigens Proteins 0.000 description 1
- 102100031573 Hematopoietic progenitor cell antigen CD34 Human genes 0.000 description 1
- 208000031220 Hemophilia Diseases 0.000 description 1
- 208000009292 Hemophilia A Diseases 0.000 description 1
- 101000615334 Homo sapiens Antileukoproteinase Proteins 0.000 description 1
- 101001095043 Homo sapiens Bone marrow proteoglycan Proteins 0.000 description 1
- 101100382122 Homo sapiens CIITA gene Proteins 0.000 description 1
- 101000761179 Homo sapiens Caspase recruitment domain-containing protein 11 Proteins 0.000 description 1
- 101000842622 Homo sapiens Derlin-3 Proteins 0.000 description 1
- 101000895701 Homo sapiens ER degradation-enhancing alpha-mannosidase-like protein 1 Proteins 0.000 description 1
- 101000777663 Homo sapiens Hematopoietic progenitor cell antigen CD34 Proteins 0.000 description 1
- 101000840258 Homo sapiens Immunoglobulin J chain Proteins 0.000 description 1
- 101000840257 Homo sapiens Immunoglobulin kappa constant Proteins 0.000 description 1
- 101001130862 Homo sapiens Oligoribonuclease, mitochondrial Proteins 0.000 description 1
- 101000891028 Homo sapiens Peptidyl-prolyl cis-trans isomerase FKBP11 Proteins 0.000 description 1
- 101001131990 Homo sapiens Peroxidasin homolog Proteins 0.000 description 1
- 101000582986 Homo sapiens Phospholipid phosphatase-related protein type 3 Proteins 0.000 description 1
- 101000919297 Homo sapiens Protein disulfide isomerase CRELD2 Proteins 0.000 description 1
- 101001098824 Homo sapiens Protein disulfide-isomerase A4 Proteins 0.000 description 1
- 101000621057 Homo sapiens Serum paraoxonase/lactonase 3 Proteins 0.000 description 1
- 101000685001 Homo sapiens Stromal cell-derived factor 2-like protein 1 Proteins 0.000 description 1
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 description 1
- 102000026659 IL10 Human genes 0.000 description 1
- 102100029571 Immunoglobulin J chain Human genes 0.000 description 1
- 102100029572 Immunoglobulin kappa constant Human genes 0.000 description 1
- 108090000174 Interleukin-10 Proteins 0.000 description 1
- 108090000172 Interleukin-15 Proteins 0.000 description 1
- 102000003812 Interleukin-15 Human genes 0.000 description 1
- 108090000978 Interleukin-4 Proteins 0.000 description 1
- 102100026371 MHC class II transactivator Human genes 0.000 description 1
- 108700002010 MHC class II transactivator Proteins 0.000 description 1
- 101100437231 Mus musculus B2m gene Proteins 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 102000011931 Nucleoproteins Human genes 0.000 description 1
- 108010061100 Nucleoproteins Proteins 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 102100032835 Oligoribonuclease, mitochondrial Human genes 0.000 description 1
- 102100024894 PR domain zinc finger protein 1 Human genes 0.000 description 1
- 102100040348 Peptidyl-prolyl cis-trans isomerase FKBP11 Human genes 0.000 description 1
- 102100034601 Peroxidasin homolog Human genes 0.000 description 1
- 108010009975 Positive Regulatory Domain I-Binding Factor 1 Proteins 0.000 description 1
- 102100029370 Protein disulfide isomerase CRELD2 Human genes 0.000 description 1
- 102100037089 Protein disulfide-isomerase A4 Human genes 0.000 description 1
- 102100022833 Serum paraoxonase/lactonase 3 Human genes 0.000 description 1
- 108091081024 Start codon Proteins 0.000 description 1
- 101000898746 Streptomyces clavuligerus Clavaminate synthase 1 Proteins 0.000 description 1
- 101000879712 Streptomyces lividans Protease inhibitor Proteins 0.000 description 1
- 102100023183 Stromal cell-derived factor 2-like protein 1 Human genes 0.000 description 1
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 1
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 description 1
- 108010043645 Transcription Activator-Like Effector Nucleases Proteins 0.000 description 1
- 108700019146 Transgenes Proteins 0.000 description 1
- 102100036922 Tumor necrosis factor ligand superfamily member 13B Human genes 0.000 description 1
- 101710181056 Tumor necrosis factor ligand superfamily member 13B Proteins 0.000 description 1
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 230000005784 autoimmunity Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000007321 biological mechanism Effects 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 230000005859 cell recognition Effects 0.000 description 1
- 238000002659 cell therapy Methods 0.000 description 1
- 230000036755 cellular response Effects 0.000 description 1
- 230000008094 contradictory effect Effects 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 229960000301 factor viii Drugs 0.000 description 1
- 238000010230 functional analysis Methods 0.000 description 1
- 238000001476 gene delivery Methods 0.000 description 1
- 238000003197 gene knockdown Methods 0.000 description 1
- 238000010363 gene targeting Methods 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 208000007345 glycogen storage disease Diseases 0.000 description 1
- 230000005745 host immune response Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000003259 immunoinhibitory effect Effects 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000004968 inflammatory condition Effects 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 1
- 230000008488 polyadenylation Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 210000001082 somatic cell Anatomy 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 230000003393 splenic effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 230000002463 transducing effect Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 108700026220 vif Genes Proteins 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70503—Immunoglobulin superfamily
- C07K14/70539—MHC-molecules, e.g. HLA-molecules
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/46—Cellular immunotherapy
- A61K39/461—Cellular immunotherapy characterised by the cell type used
- A61K39/4612—B-cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/46—Cellular immunotherapy
- A61K39/462—Cellular immunotherapy characterized by the effect or the function of the cells
- A61K39/4621—Cellular immunotherapy characterized by the effect or the function of the cells immunosuppressive or immunotolerising
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/46—Cellular immunotherapy
- A61K39/462—Cellular immunotherapy characterized by the effect or the function of the cells
- A61K39/4622—Antigen presenting cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/46—Cellular immunotherapy
- A61K39/464—Cellular immunotherapy characterised by the antigen targeted or presented
- A61K39/4643—Vertebrate antigens
- A61K39/46434—Antigens related to induction of tolerance to non-self
-
- 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
- C12N15/87—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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2239/00—Indexing codes associated with cellular immunotherapy of group A61K39/46
- A61K2239/26—Universal/off- the- shelf cellular immunotherapy; Allogenic cells or means to avoid rejection
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/60—Fusion polypeptide containing spectroscopic/fluorescent detection, e.g. green fluorescent protein [GFP]
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/10—Type of nucleic acid
- C12N2310/20—Type of nucleic acid involving clustered regularly interspaced short palindromic repeats [CRISPRs]
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- 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
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Genetics & Genomics (AREA)
- Cell Biology (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Microbiology (AREA)
- Immunology (AREA)
- Zoology (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- Medicinal Chemistry (AREA)
- Mycology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biotechnology (AREA)
- Wood Science & Technology (AREA)
- General Engineering & Computer Science (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Plant Pathology (AREA)
- Physics & Mathematics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Toxicology (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Document Processing Apparatus (AREA)
- Virology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Hematology (AREA)
- Developmental Biology & Embryology (AREA)
- Crystallography & Structural Chemistry (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US202063047978P | 2020-07-03 | 2020-07-03 | |
| US63/047,978 | 2020-07-03 | ||
| US202063114131P | 2020-11-16 | 2020-11-16 | |
| US63/114,131 | 2020-11-16 | ||
| PCT/US2021/039953 WO2022006309A1 (en) | 2020-07-03 | 2021-06-30 | Methods and compositions for editing the b2m locus in b cells |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AU2021300358A1 true AU2021300358A1 (en) | 2023-02-02 |
Family
ID=79315579
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2021300358A Pending AU2021300358A1 (en) | 2020-07-03 | 2021-06-30 | Methods and compositions for editing the B2M locus in B cells |
Country Status (10)
| Country | Link |
|---|---|
| EP (1) | EP4175651A1 (ko) |
| JP (1) | JP2023532917A (ko) |
| KR (1) | KR20230035048A (ko) |
| CN (1) | CN116033910A (ko) |
| AU (1) | AU2021300358A1 (ko) |
| BR (1) | BR112022026534A2 (ko) |
| CA (1) | CA3186620A1 (ko) |
| IL (1) | IL299491A (ko) |
| MX (1) | MX2022015788A (ko) |
| WO (1) | WO2022006309A1 (ko) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2024030857A1 (en) * | 2022-08-01 | 2024-02-08 | Idexx Laboratories, Inc. | Human mouse fractional abundance assays |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL297018A (en) * | 2015-12-18 | 2022-12-01 | Sangamo Therapeutics Inc | Directed cleavage of cell mhc receptor |
| EP3645036A1 (en) * | 2017-06-30 | 2020-05-06 | Cellectis | Cellular immunotherapy for repetitive administration |
-
2021
- 2021-06-30 WO PCT/US2021/039953 patent/WO2022006309A1/en active Application Filing
- 2021-06-30 AU AU2021300358A patent/AU2021300358A1/en active Pending
- 2021-06-30 EP EP21832140.4A patent/EP4175651A1/en active Pending
- 2021-06-30 CA CA3186620A patent/CA3186620A1/en active Pending
- 2021-06-30 JP JP2022581341A patent/JP2023532917A/ja active Pending
- 2021-06-30 MX MX2022015788A patent/MX2022015788A/es unknown
- 2021-06-30 CN CN202180047549.4A patent/CN116033910A/zh active Pending
- 2021-06-30 IL IL299491A patent/IL299491A/en unknown
- 2021-06-30 KR KR1020237001885A patent/KR20230035048A/ko unknown
- 2021-06-30 BR BR112022026534A patent/BR112022026534A2/pt unknown
Also Published As
| Publication number | Publication date |
|---|---|
| KR20230035048A (ko) | 2023-03-10 |
| EP4175651A1 (en) | 2023-05-10 |
| CA3186620A1 (en) | 2022-01-06 |
| MX2022015788A (es) | 2023-02-27 |
| BR112022026534A2 (pt) | 2023-04-18 |
| IL299491A (en) | 2023-02-01 |
| JP2023532917A (ja) | 2023-08-01 |
| WO2022006309A1 (en) | 2022-01-06 |
| CN116033910A (zh) | 2023-04-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP7391016B2 (ja) | 全身免疫抑制を必要としない同種免疫寛容 | |
| AU2016291778B2 (en) | Delivery methods and compositions for nuclease-mediated genome engineering | |
| US20240033300A1 (en) | Method for treating autoimmune disease using cd4 t-cells with engineered stabilization of expression of endogenous foxp3 gene | |
| CA3081456A1 (en) | Methods, compositions and components for crispr-cas9 editing of tgfbr2 in t cells for immunotherapy | |
| CA3091688A1 (en) | Expression of foxp3 in edited cd34+ cells | |
| AU2018264636B2 (en) | Artificially manipulated immune cell | |
| CA3091491A1 (en) | Expression of human foxp3 in gene edited t cells | |
| CA3145037A1 (en) | Artificial antigen-specific immunoregulatory t (airt) cells | |
| WO2022006309A1 (en) | Methods and compositions for editing the b2m locus in b cells | |
| WO2022132765A1 (en) | Biallelic knockout of b2m | |
| JP2021500080A (ja) | 高ＩｇＭ症候群を処置するためのシステム及び方法 | |
| US20230272431A1 (en) | Methods and compositions for editing the b2m locus in b cells | |
| AU2021411521A1 (en) | Engineered t cells | |
| JP2023547887A (ja) | セーフハーバー遺伝子座 | |
| WO2024035900A2 (en) | Methods and compositions for transducing hematopoietic cells | |
| WO2023070126A1 (en) | Genetically engineered t cell receptors | |
| AU2020370254A1 (en) | Transgenic swine, methods of making and uses thereof, and methods of making human immune system mice | |
| CN117957327A (zh) | 用于基于细胞的疗法的多顺反子载体 | |
| CN114807155A (zh) | 用于基因编辑的组合物及其应用 |