CA2942268A1 - Dystrophin gene exon deletion using engineered nucleases - Google Patents
Dystrophin gene exon deletion using engineered nucleases Download PDFInfo
- Publication number
- CA2942268A1 CA2942268A1 CA2942268A CA2942268A CA2942268A1 CA 2942268 A1 CA2942268 A1 CA 2942268A1 CA 2942268 A CA2942268 A CA 2942268A CA 2942268 A CA2942268 A CA 2942268A CA 2942268 A1 CA2942268 A1 CA 2942268A1
- Authority
- CA
- Canada
- Prior art keywords
- exon
- seq
- dna
- sequence
- nucleases
- 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
- 101710163270 Nuclease Proteins 0.000 title claims abstract description 77
- 108010069091 Dystrophin Proteins 0.000 title claims abstract description 21
- 238000012217 deletion Methods 0.000 title description 31
- 230000037430 deletion Effects 0.000 title description 31
- 238000000034 method Methods 0.000 claims abstract description 45
- 206010013801 Duchenne Muscular Dystrophy Diseases 0.000 claims abstract description 19
- 210000004027 cell Anatomy 0.000 claims description 83
- 108020004414 DNA Proteins 0.000 claims description 68
- 108090000623 proteins and genes Proteins 0.000 claims description 50
- 108091033409 CRISPR Proteins 0.000 claims description 27
- 238000010354 CRISPR gene editing Methods 0.000 claims description 18
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 16
- 238000010459 TALEN Methods 0.000 claims description 13
- 108010043645 Transcription Activator-Like Effector Nucleases Proteins 0.000 claims description 13
- 238000011144 upstream manufacturing Methods 0.000 claims description 8
- 210000000663 muscle cell Anatomy 0.000 claims description 6
- 241000702421 Dependoparvovirus Species 0.000 claims description 4
- 150000007523 nucleic acids Chemical class 0.000 abstract description 14
- 102000039446 nucleic acids Human genes 0.000 abstract description 13
- 108020004707 nucleic acids Proteins 0.000 abstract description 13
- 238000005516 engineering process Methods 0.000 abstract description 5
- 239000000047 product Substances 0.000 description 33
- 102100024108 Dystrophin Human genes 0.000 description 32
- 101100443350 Mus musculus Dmd gene Proteins 0.000 description 32
- 108010042407 Endonucleases Proteins 0.000 description 22
- 102000004533 Endonucleases Human genes 0.000 description 22
- 238000003776 cleavage reaction Methods 0.000 description 19
- 101150015424 dmd gene Proteins 0.000 description 19
- 108020004999 messenger RNA Proteins 0.000 description 19
- 230000007017 scission Effects 0.000 description 19
- 108700024394 Exon Proteins 0.000 description 17
- 210000003205 muscle Anatomy 0.000 description 17
- 239000013612 plasmid Substances 0.000 description 17
- 102000004169 proteins and genes Human genes 0.000 description 17
- 230000000295 complement effect Effects 0.000 description 16
- 239000012634 fragment Substances 0.000 description 16
- 230000035772 mutation Effects 0.000 description 16
- 239000013598 vector Substances 0.000 description 14
- 108010050663 endodeoxyribonuclease CreI Proteins 0.000 description 13
- 230000007018 DNA scission Effects 0.000 description 12
- 102000001039 Dystrophin Human genes 0.000 description 12
- 210000000349 chromosome Anatomy 0.000 description 12
- 108020005004 Guide RNA Proteins 0.000 description 11
- 238000013459 approach Methods 0.000 description 11
- 210000004899 c-terminal region Anatomy 0.000 description 11
- 101150116409 dys-1 gene Proteins 0.000 description 11
- 230000004568 DNA-binding Effects 0.000 description 10
- 241000699666 Mus <mouse, genus> Species 0.000 description 10
- 230000014509 gene expression Effects 0.000 description 10
- 108090000765 processed proteins & peptides Proteins 0.000 description 9
- 101000889900 Enterobacteria phage T4 Intron-associated endonuclease 1 Proteins 0.000 description 8
- 241000700605 Viruses Species 0.000 description 8
- 239000000178 monomer Substances 0.000 description 7
- 230000008439 repair process Effects 0.000 description 7
- 101150066002 GFP gene Proteins 0.000 description 6
- 108010073062 Transcription Activator-Like Effectors Proteins 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
- 238000011282 treatment Methods 0.000 description 6
- 239000013603 viral vector Substances 0.000 description 6
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 5
- 230000033616 DNA repair Effects 0.000 description 5
- 108010017070 Zinc Finger Nucleases Proteins 0.000 description 5
- 238000003556 assay Methods 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 238000005304 joining Methods 0.000 description 5
- 230000007246 mechanism Effects 0.000 description 5
- 210000003098 myoblast Anatomy 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- 230000002441 reversible effect Effects 0.000 description 5
- 239000013607 AAV vector Substances 0.000 description 4
- 102000011727 Caspases Human genes 0.000 description 4
- 108010076667 Caspases Proteins 0.000 description 4
- 102000053602 DNA Human genes 0.000 description 4
- 108020004485 Nonsense Codon Proteins 0.000 description 4
- 238000000246 agarose gel electrophoresis Methods 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 239000000499 gel Substances 0.000 description 4
- 238000002744 homologous recombination Methods 0.000 description 4
- 230000006801 homologous recombination Effects 0.000 description 4
- 231100000219 mutagenic Toxicity 0.000 description 4
- 230000003505 mutagenic effect Effects 0.000 description 4
- 102000004196 processed proteins & peptides Human genes 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 238000001890 transfection Methods 0.000 description 4
- 108091026890 Coding region Proteins 0.000 description 3
- 108091092195 Intron Proteins 0.000 description 3
- 239000011543 agarose gel Substances 0.000 description 3
- 125000003275 alpha amino acid group Chemical group 0.000 description 3
- 238000000137 annealing Methods 0.000 description 3
- 230000001580 bacterial effect Effects 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 230000004186 co-expression Effects 0.000 description 3
- 238000006471 dimerization reaction Methods 0.000 description 3
- 230000011559 double-strand break repair via nonhomologous end joining Effects 0.000 description 3
- 230000037433 frameshift Effects 0.000 description 3
- 238000010353 genetic engineering Methods 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 230000001939 inductive effect Effects 0.000 description 3
- 238000003780 insertion Methods 0.000 description 3
- 230000037431 insertion Effects 0.000 description 3
- 239000002502 liposome Substances 0.000 description 3
- 230000006780 non-homologous end joining Effects 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 229920001184 polypeptide Polymers 0.000 description 3
- 230000008685 targeting Effects 0.000 description 3
- 230000003612 virological effect Effects 0.000 description 3
- 241001655883 Adeno-associated virus - 1 Species 0.000 description 2
- 241000702423 Adeno-associated virus - 2 Species 0.000 description 2
- 108010008532 Deoxyribonuclease I Proteins 0.000 description 2
- 102000007260 Deoxyribonuclease I Human genes 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 108020004684 Internal Ribosome Entry Sites Proteins 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 108091034117 Oligonucleotide Proteins 0.000 description 2
- 238000002123 RNA extraction Methods 0.000 description 2
- 238000012300 Sequence Analysis Methods 0.000 description 2
- 108020004682 Single-Stranded DNA Proteins 0.000 description 2
- 102000005890 Spectrin Human genes 0.000 description 2
- 108010019965 Spectrin Proteins 0.000 description 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 230000027455 binding Effects 0.000 description 2
- 230000033077 cellular process Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 229960001231 choline Drugs 0.000 description 2
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 2
- 238000010367 cloning Methods 0.000 description 2
- 238000012761 co-transfection Methods 0.000 description 2
- 210000004748 cultured cell Anatomy 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000000684 flow cytometry Methods 0.000 description 2
- 230000004927 fusion Effects 0.000 description 2
- 238000001476 gene delivery Methods 0.000 description 2
- 239000000833 heterodimer Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000010255 intramuscular injection Methods 0.000 description 2
- 239000007927 intramuscular injection Substances 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 238000010172 mouse model Methods 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- 230000037434 nonsense mutation Effects 0.000 description 2
- 238000004806 packaging method and process Methods 0.000 description 2
- 230000000717 retained effect Effects 0.000 description 2
- 230000003007 single stranded DNA break Effects 0.000 description 2
- 210000002027 skeletal muscle Anatomy 0.000 description 2
- 238000013518 transcription Methods 0.000 description 2
- 230000035897 transcription Effects 0.000 description 2
- 230000009261 transgenic effect Effects 0.000 description 2
- 239000011701 zinc Substances 0.000 description 2
- 229910052725 zinc Inorganic materials 0.000 description 2
- 201000006935 Becker muscular dystrophy Diseases 0.000 description 1
- 108010051109 Cell-Penetrating Peptides Proteins 0.000 description 1
- 102000020313 Cell-Penetrating Peptides Human genes 0.000 description 1
- 241000195597 Chlamydomonas reinhardtii Species 0.000 description 1
- 108020004705 Codon Proteins 0.000 description 1
- 102000004420 Creatine Kinase Human genes 0.000 description 1
- 108010042126 Creatine kinase Proteins 0.000 description 1
- 241000195493 Cryptophyta Species 0.000 description 1
- 102000012410 DNA Ligases Human genes 0.000 description 1
- 108010061982 DNA Ligases Proteins 0.000 description 1
- 231100001074 DNA strand break Toxicity 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 102100025682 Dystroglycan 1 Human genes 0.000 description 1
- 108010071885 Dystroglycans Proteins 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- MAJYPBAJPNUFPV-BQBZGAKWSA-N His-Cys Chemical compound SC[C@@H](C(O)=O)NC(=O)[C@@H](N)CC1=CN=CN1 MAJYPBAJPNUFPV-BQBZGAKWSA-N 0.000 description 1
- 101001000998 Homo sapiens Protein phosphatase 1 regulatory subunit 12C Proteins 0.000 description 1
- 241000700588 Human alphaherpesvirus 1 Species 0.000 description 1
- 241000725303 Human immunodeficiency virus Species 0.000 description 1
- 239000000232 Lipid Bilayer Substances 0.000 description 1
- 102000002151 Microfilament Proteins Human genes 0.000 description 1
- 108010040897 Microfilament Proteins Proteins 0.000 description 1
- 206010028289 Muscle atrophy Diseases 0.000 description 1
- 108010088535 Pep-1 peptide Proteins 0.000 description 1
- 102100035620 Protein phosphatase 1 regulatory subunit 12C Human genes 0.000 description 1
- 108020005067 RNA Splice Sites Proteins 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 108091061939 Selfish DNA Proteins 0.000 description 1
- 210000001766 X chromosome Anatomy 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 Chemical class 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
- AIYUHDOJVYHVIT-UHFFFAOYSA-M caesium chloride Chemical compound [Cl-].[Cs+] AIYUHDOJVYHVIT-UHFFFAOYSA-M 0.000 description 1
- 210000004413 cardiac myocyte Anatomy 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000004700 cellular uptake Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 229940098124 cesium chloride Drugs 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 210000003763 chloroplast Anatomy 0.000 description 1
- 239000013611 chromosomal DNA Substances 0.000 description 1
- 230000002759 chromosomal effect Effects 0.000 description 1
- 238000005520 cutting process Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000003412 degenerative effect Effects 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 230000005782 double-strand break Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 238000012246 gene addition Methods 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 238000012248 genetic selection Methods 0.000 description 1
- 239000000710 homodimer Substances 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 230000008105 immune reaction Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 238000002743 insertional mutagenesis Methods 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 230000017730 intein-mediated protein splicing Effects 0.000 description 1
- 210000003141 lower extremity Anatomy 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 210000003130 muscle precursor cell Anatomy 0.000 description 1
- 210000004165 myocardium Anatomy 0.000 description 1
- 210000001087 myotubule Anatomy 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 108010011110 polyarginine Proteins 0.000 description 1
- 108020001580 protein domains Proteins 0.000 description 1
- 230000003252 repetitive effect Effects 0.000 description 1
- 230000003362 replicative effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- 238000002864 sequence alignment Methods 0.000 description 1
- 238000002741 site-directed mutagenesis Methods 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 1
- 125000006850 spacer group Chemical group 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/465—Hydrolases (3) acting on ester bonds (3.1), e.g. lipases, ribonucleases
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/54—Mixtures of enzymes or proenzymes covered by more than a single one of groups A61K38/44 - A61K38/46 or A61K38/51 - A61K38/53
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
- A61K48/005—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/04—Drugs for disorders of the muscular or neuromuscular system for myasthenia gravis
-
- 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
-
- 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
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
- C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
- C07K14/4707—Muscular dystrophy
- C07K14/4708—Duchenne dystrophy
-
- 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
- C12N7/00—Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof
-
- 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
- C12N2750/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssDNA viruses
- C12N2750/00011—Details
- C12N2750/14011—Parvoviridae
- C12N2750/14111—Dependovirus, e.g. adenoassociated viruses
- C12N2750/14141—Use of virus, viral particle or viral elements as a vector
- C12N2750/14143—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Organic Chemistry (AREA)
- Genetics & Genomics (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Molecular Biology (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Epidemiology (AREA)
- Biotechnology (AREA)
- Biochemistry (AREA)
- Biomedical Technology (AREA)
- Microbiology (AREA)
- General Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Neurology (AREA)
- Physical Education & Sports Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Virology (AREA)
- Toxicology (AREA)
- Biophysics (AREA)
- Enzymes And Modification Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201461951648P | 2014-03-12 | 2014-03-12 | |
| US61/951,648 | 2014-03-12 | ||
| PCT/US2015/020205 WO2015138739A2 (en) | 2014-03-12 | 2015-03-12 | Dystrophin gene oxon deletion using engineered nucleases |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2942268A1 true CA2942268A1 (en) | 2015-09-17 |
Family
ID=54072591
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2942268A Pending CA2942268A1 (en) | 2014-03-12 | 2015-03-12 | Dystrophin gene exon deletion using engineered nucleases |
Country Status (8)
| Country | Link |
|---|---|
| US (6) | US20170106055A1 (enExample) |
| EP (3) | EP3116533B1 (enExample) |
| JP (5) | JP2017512767A (enExample) |
| AU (3) | AU2015229299A1 (enExample) |
| CA (1) | CA2942268A1 (enExample) |
| DK (1) | DK3116533T3 (enExample) |
| ES (2) | ES3037550T3 (enExample) |
| WO (1) | WO2015138739A2 (enExample) |
Families Citing this family (53)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10323236B2 (en) | 2011-07-22 | 2019-06-18 | President And Fellows Of Harvard College | Evaluation and improvement of nuclease cleavage specificity |
| SI2986729T1 (sl) | 2013-04-16 | 2019-02-28 | Regeneron Pharmaceuticals, Inc. | Ciljana sprememba genoma podgane |
| US9163284B2 (en) | 2013-08-09 | 2015-10-20 | President And Fellows Of Harvard College | Methods for identifying a target site of a Cas9 nuclease |
| US9359599B2 (en) | 2013-08-22 | 2016-06-07 | President And Fellows Of Harvard College | Engineered transcription activator-like effector (TALE) domains and uses thereof |
| US9322037B2 (en) | 2013-09-06 | 2016-04-26 | President And Fellows Of Harvard College | Cas9-FokI fusion proteins and uses thereof |
| US9526784B2 (en) | 2013-09-06 | 2016-12-27 | President And Fellows Of Harvard College | Delivery system for functional nucleases |
| US9340799B2 (en) | 2013-09-06 | 2016-05-17 | President And Fellows Of Harvard College | MRNA-sensing switchable gRNAs |
| EP4372090A3 (en) | 2013-11-07 | 2024-08-07 | Editas Medicine, Inc. | Crispr-related methods and compositions with governing grnas |
| CN110951779B (zh) | 2013-12-11 | 2024-04-16 | 瑞泽恩制药公司 | 用于靶向修饰基因组的方法和组合物 |
| US11053481B2 (en) | 2013-12-12 | 2021-07-06 | President And Fellows Of Harvard College | Fusions of Cas9 domains and nucleic acid-editing domains |
| EP4079847A1 (en) | 2014-07-30 | 2022-10-26 | President And Fellows Of Harvard College | Cas9 proteins including ligand-dependent inteins |
| BR112017010547A2 (pt) | 2014-11-21 | 2018-02-27 | Regeneron Pharma | métodos para produção de uma modificação bialélica, modificação de um genoma dentro de uma célula, produção de uma geração f0 de um animal não humano e identificação de uma inserção de um inserto de ácido nucleico. |
| WO2016089866A1 (en) * | 2014-12-01 | 2016-06-09 | President And Fellows Of Harvard College | Rna-guided systems for in vivo gene editing |
| WO2016161380A1 (en) * | 2015-04-01 | 2016-10-06 | Editas Medicine, Inc. | Crispr/cas-related methods and compositions for treating duchenne muscular dystrophy and becker muscular dystrophy |
| EP4530354A3 (en) * | 2015-09-08 | 2025-09-10 | Precision Biosciences, Inc. | Treatment of retinitis pigmentosa using engineered meganucleases |
| AU2016333898B2 (en) | 2015-10-05 | 2020-11-12 | Precision Biosciences, Inc. | Genetically-modified cells comprising a modified human T cell receptor alpha constant region gene |
| ES2768984T3 (es) | 2015-10-05 | 2020-06-24 | Prec Biosciences Inc | Meganucleasas diseñadas con secuencias de reconocimiento encontradas en el gen de la región constante alfa del receptor de células T humanas |
| IL294014B2 (en) | 2015-10-23 | 2024-07-01 | Harvard College | Nucleobase editors and uses thereof |
| IL262888B1 (en) | 2016-05-20 | 2025-10-01 | Regeneron Pharma | Methods for breaking immunological tolerance using multiple guide RNAs |
| WO2018027078A1 (en) | 2016-08-03 | 2018-02-08 | President And Fellows Of Harard College | Adenosine nucleobase editors and uses thereof |
| US11661590B2 (en) | 2016-08-09 | 2023-05-30 | President And Fellows Of Harvard College | Programmable CAS9-recombinase fusion proteins and uses thereof |
| US11542509B2 (en) | 2016-08-24 | 2023-01-03 | President And Fellows Of Harvard College | Incorporation of unnatural amino acids into proteins using base editing |
| SG11201903089RA (en) | 2016-10-14 | 2019-05-30 | Harvard College | Aav delivery of nucleobase editors |
| WO2018098480A1 (en) * | 2016-11-28 | 2018-05-31 | The Board Of Regents Of The University Of Texas System | Prevention of muscular dystrophy by crispr/cpf1-mediated gene editing |
| US10745677B2 (en) | 2016-12-23 | 2020-08-18 | President And Fellows Of Harvard College | Editing of CCR5 receptor gene to protect against HIV infection |
| JOP20190166A1 (ar) * | 2017-01-05 | 2019-07-02 | Univ Texas | استراتيجية مثلى من أجل تعديلات تخطي إكسون باستخدام crispr/cas9 مع متواليات توجيه ثلاثي |
| EP3592381A1 (en) | 2017-03-09 | 2020-01-15 | President and Fellows of Harvard College | Cancer vaccine |
| EP3592853A1 (en) | 2017-03-09 | 2020-01-15 | President and Fellows of Harvard College | Suppression of pain by gene editing |
| CN110914310A (zh) | 2017-03-10 | 2020-03-24 | 哈佛大学的校长及成员们 | 胞嘧啶至鸟嘌呤碱基编辑器 |
| GB2575930A (en) | 2017-03-23 | 2020-01-29 | Harvard College | Nucleobase editors comprising nucleic acid programmable DNA binding proteins |
| AU2017407272B2 (en) * | 2017-03-30 | 2024-06-13 | Kyoto University | Method for inducing exon skipping by genome editing |
| WO2018209320A1 (en) | 2017-05-12 | 2018-11-15 | President And Fellows Of Harvard College | Aptazyme-embedded guide rnas for use with crispr-cas9 in genome editing and transcriptional activation |
| CA3068465A1 (en) | 2017-06-30 | 2019-01-03 | Precision Biosciences, Inc. | Genetically-modified t cells comprising a modified intron in the t cell receptor alpha gene |
| US11732274B2 (en) | 2017-07-28 | 2023-08-22 | President And Fellows Of Harvard College | Methods and compositions for evolving base editors using phage-assisted continuous evolution (PACE) |
| EP3676376B1 (en) | 2017-08-30 | 2025-01-15 | President and Fellows of Harvard College | High efficiency base editors comprising gam |
| WO2019079347A1 (en) | 2017-10-16 | 2019-04-25 | The Broad Institute, Inc. | USES OF BASIC EDITORS ADENOSINE |
| WO2019118949A1 (en) | 2017-12-15 | 2019-06-20 | The Broad Institute, Inc. | Systems and methods for predicting repair outcomes in genetic engineering |
| KR102617818B1 (ko) | 2018-04-12 | 2023-12-27 | 프리시젼 바이오사이언시스 인코포레이티드 | 인간 t 세포 수용체 알파 불변 영역 유전자에 대한 특이성을 갖는 최적화된 조작된 뉴클레아제 |
| WO2019226953A1 (en) | 2018-05-23 | 2019-11-28 | The Broad Institute, Inc. | Base editors and uses thereof |
| WO2020092453A1 (en) | 2018-10-29 | 2020-05-07 | The Broad Institute, Inc. | Nucleobase editors comprising geocas9 and uses thereof |
| EP3884063B1 (en) * | 2018-11-19 | 2023-11-01 | Altius Institute For Biomedical Sciences | Compositions and methods for detection of cleavage of genomic dna by a nuclease |
| US12351837B2 (en) | 2019-01-23 | 2025-07-08 | The Broad Institute, Inc. | Supernegatively charged proteins and uses thereof |
| DE112020001342T5 (de) | 2019-03-19 | 2022-01-13 | President and Fellows of Harvard College | Verfahren und Zusammensetzungen zum Editing von Nukleotidsequenzen |
| WO2020214842A1 (en) | 2019-04-17 | 2020-10-22 | The Broad Institute, Inc. | Adenine base editors with reduced off-target effects |
| CA3137975A1 (en) | 2019-05-07 | 2020-11-12 | Precision Biosciences, Inc. | Optimization of engineered meganucleases for recognition sequences |
| WO2021072328A1 (en) | 2019-10-10 | 2021-04-15 | The Broad Institute, Inc. | Methods and compositions for prime editing rna |
| KR20220164743A (ko) * | 2020-04-06 | 2022-12-13 | 호몰로지 메디슨, 인크. | Ids 유전자 전달을 위한 아데노-연관 바이러스 조성물 및 이의 사용 방법 |
| EP4143308A4 (en) * | 2020-04-27 | 2024-06-26 | The Trustees of The University of Pennsylvania | COMPOSITIONS AND METHODS FOR REDUCING NUCLEASE EXPRESSION AND OFF-TARGET ACTIVITY USING A PROMOTER WITH LOW TRANSCRIPTION ACTIVITY |
| GB2614813B (en) | 2020-05-08 | 2025-05-07 | Harvard College | Methods and compositions for simultaneous editing of both strands of a target double-stranded nucleotide sequence |
| WO2021231259A1 (en) | 2020-05-11 | 2021-11-18 | Precision Biosciences, Inc. | Self-limiting viral vectors encoding nucleases |
| EP4244342A1 (en) | 2020-11-12 | 2023-09-20 | Precision BioSciences, Inc. | Engineered meganucleases having specificity for recognition sequences in the dystrophin gene |
| EP4444886A1 (en) * | 2021-12-08 | 2024-10-16 | Mammoth Biosciences, Inc. | Systems and uses thereof for the treatment of dmd-associated diseases |
| JP7691595B1 (ja) | 2024-02-26 | 2025-06-12 | 株式会社ニチレイフーズ | 欠失した改変ゲノムｄｎａを含む細胞の作製方法、該細胞を含む生物体の作製方法 |
Family Cites Families (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2006518372A (ja) * | 2003-01-28 | 2006-08-10 | セレクティス | 脊椎動物の体組織においてエクスビボかつイントトで相同的組換えを誘発するためのメガヌクレアーゼの使用およびその応用 |
| US8021867B2 (en) | 2005-10-18 | 2011-09-20 | Duke University | Rationally-designed meganucleases with altered sequence specificity and DNA-binding affinity |
| EP3578646A3 (en) | 2007-10-31 | 2020-03-18 | Precision Biosciences, Inc. | Rationally-designed single-chain meganucleases with non-palindromic recognition sequences |
| WO2009101399A1 (en) * | 2008-02-12 | 2009-08-20 | Isis Innovation Limited | Treatment of muscular dystrophy using peptide nucleic acid ( pna) |
| ES2625941T3 (es) | 2008-07-14 | 2017-07-21 | Precision Biosciences, Inc. | Secuencias de reconocimiento para meganucleasas derivadas de i-crei y sus usos |
| EP2480659A2 (en) * | 2009-09-24 | 2012-08-01 | Cellectis | Meganuclease reagents of uses thereof for treating genetic diseases caused by frame shift/non sense mutations |
| SG169914A1 (en) * | 2009-09-29 | 2011-04-29 | Univ Singapore | A clinical method for genotyping large genes for mutations that potentially cause disease |
| CA2799095A1 (en) * | 2010-05-12 | 2011-11-17 | Cellectis | Meganuclease variants cleaving a dna target sequence from the dystrophin gene and uses thereof |
| CA2815512A1 (en) * | 2010-10-27 | 2012-05-03 | Philippe Duchateau | Method for increasing the efficiency of double-strand break-induced mutagenesis |
| DK2714936T3 (en) * | 2011-06-01 | 2019-03-25 | Prec Biosciences Inc | METHODS AND PRODUCTS FOR PRODUCING MANIPULATED MAMMAL CELL LINES WITH AMPLIFIED TRANSGENES |
| CA2851388C (en) * | 2011-10-10 | 2023-11-21 | The Hospital For Sick Children | Methods and compositions for screening and treating developmental disorders |
| US8885683B2 (en) * | 2011-12-21 | 2014-11-11 | Canon Kabushiki Kaisha | Process for forming microstructure of nitride semiconductor, surface emitting laser using two-dimensional photonic crystal and production process thereof |
| WO2013163628A2 (en) * | 2012-04-27 | 2013-10-31 | Duke University | Genetic correction of mutated genes |
| EP2684892A1 (en) * | 2012-07-13 | 2014-01-15 | Association Française contre les Myopathies | Compositions and methods for duchenne muscular dystrophy gene therapy |
| WO2014071219A1 (en) * | 2012-11-01 | 2014-05-08 | Factor Bioscience Inc. | Methods and products for expressing proteins in cells |
| US8697359B1 (en) * | 2012-12-12 | 2014-04-15 | The Broad Institute, Inc. | CRISPR-Cas systems and methods for altering expression of gene products |
| ES2991293T3 (es) * | 2013-06-05 | 2024-12-03 | Univ Duke | Edición génica guiada por ARN y regulación génica |
| CA2878645C (en) | 2014-01-22 | 2017-02-21 | Alfa Wassermann, Inc. | Centrifugation systems with non-contact seal assemblies |
| EP4279084B1 (en) * | 2015-10-28 | 2025-06-11 | Vertex Pharmaceuticals Inc. | Materials and methods for treatment of duchenne muscular dystrophy |
| EP4244342A1 (en) * | 2020-11-12 | 2023-09-20 | Precision BioSciences, Inc. | Engineered meganucleases having specificity for recognition sequences in the dystrophin gene |
-
2015
- 2015-03-12 EP EP15761320.9A patent/EP3116533B1/en active Active
- 2015-03-12 CA CA2942268A patent/CA2942268A1/en active Pending
- 2015-03-12 ES ES20189872T patent/ES3037550T3/es active Active
- 2015-03-12 WO PCT/US2015/020205 patent/WO2015138739A2/en not_active Ceased
- 2015-03-12 US US15/124,984 patent/US20170106055A1/en not_active Abandoned
- 2015-03-12 EP EP25191909.8A patent/EP4659765A2/en active Pending
- 2015-03-12 JP JP2016556801A patent/JP2017512767A/ja active Pending
- 2015-03-12 DK DK15761320.9T patent/DK3116533T3/da active
- 2015-03-12 EP EP20189872.3A patent/EP3858376B1/en active Active
- 2015-03-12 AU AU2015229299A patent/AU2015229299A1/en not_active Abandoned
- 2015-03-12 ES ES15761320T patent/ES2821149T3/es active Active
-
2019
- 2019-02-25 US US16/284,733 patent/US20190269762A1/en not_active Abandoned
- 2019-07-03 US US16/503,396 patent/US20190365870A1/en not_active Abandoned
- 2019-08-23 JP JP2019152614A patent/JP6832995B2/ja active Active
-
2020
- 2020-09-25 US US17/033,331 patent/US20210145940A1/en not_active Abandoned
- 2020-10-26 AU AU2020260387A patent/AU2020260387A1/en not_active Abandoned
-
2021
- 2021-02-02 JP JP2021014851A patent/JP2021088563A/ja active Pending
-
2022
- 2022-09-28 JP JP2022154637A patent/JP2023002555A/ja active Pending
-
2023
- 2023-10-19 US US18/490,484 patent/US20240156919A1/en not_active Abandoned
-
2024
- 2024-04-02 AU AU2024202080A patent/AU2024202080A1/en active Pending
- 2024-09-27 JP JP2024168117A patent/JP2025013784A/ja active Pending
-
2025
- 2025-01-17 US US19/030,187 patent/US20250152679A1/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| US20240156919A1 (en) | 2024-05-16 |
| EP3116533B1 (en) | 2020-08-12 |
| EP3858376C0 (en) | 2025-07-30 |
| WO2015138739A8 (en) | 2015-11-19 |
| AU2020260387A1 (en) | 2020-11-19 |
| WO2015138739A2 (en) | 2015-09-17 |
| US20190365870A1 (en) | 2019-12-05 |
| US20190269762A1 (en) | 2019-09-05 |
| EP3116533A2 (en) | 2017-01-18 |
| US20170106055A1 (en) | 2017-04-20 |
| ES3037550T3 (en) | 2025-10-03 |
| JP2023002555A (ja) | 2023-01-10 |
| JP6832995B2 (ja) | 2021-02-24 |
| EP3116533A4 (en) | 2018-04-18 |
| AU2024202080A1 (en) | 2024-04-18 |
| JP2025013784A (ja) | 2025-01-28 |
| AU2015229299A1 (en) | 2016-09-22 |
| US20210145940A1 (en) | 2021-05-20 |
| EP4659765A2 (en) | 2025-12-10 |
| US20250152679A1 (en) | 2025-05-15 |
| WO2015138739A3 (en) | 2015-10-22 |
| JP2017512767A (ja) | 2017-05-25 |
| EP3858376B1 (en) | 2025-07-30 |
| EP3858376A1 (en) | 2021-08-04 |
| JP2021088563A (ja) | 2021-06-10 |
| DK3116533T3 (da) | 2020-08-24 |
| ES2821149T3 (es) | 2021-04-23 |
| JP2019214609A (ja) | 2019-12-19 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP3858376B1 (en) | Dystrophin gene exon deletion using engineered nucleases | |
| US20250114482A1 (en) | Therapeutic applications of cpf1-based genome editing | |
| EP3452498B1 (en) | Crispr/cas-related compositions for treating duchenne muscular dystrophy | |
| US8802437B2 (en) | Meganuclease reagents of uses thereof for treating genetic diseases caused by frame shift/non sense mutations | |
| US12214054B2 (en) | Therapeutic targets for the correction of the human dystrophin gene by gene editing and methods of use | |
| JP2022529631A (ja) | デュシェンヌ型筋ジストロフィーの処置のための大きい突然変異ホットスポットのａａｖベクター媒介欠失 | |
| EP3930766A1 (en) | Crispr/cas-based genome editing composition for restoring dystrophin function | |
| EP4126073A1 (en) | Crispr/cas9 therapies for correcting duchenne muscular dystrophy by targeted genomic integration | |
| HK40057044A (en) | Dystrophin gene exon deletion using engineered nucleases | |
| CA3202411A1 (en) | Therapeutic lama2 payload for treatment of congenital muscular dystrophy | |
| HK40004669A (en) | Therapeutic applications of cpf1-based genome editing | |
| HK40004669B (en) | Therapeutic applications of cpf1-based genome editing |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |
Effective date: 20200310 |
|
| EEER | Examination request |
Effective date: 20200310 |
|
| EEER | Examination request |
Effective date: 20200310 |
|
| EEER | Examination request |
Effective date: 20200310 |
|
| EEER | Examination request |
Effective date: 20200310 |
|
| EEER | Examination request |
Effective date: 20200310 |