JP2018143253A - 配列操作のための改善された系、方法および酵素組成物のエンジニアリングおよび最適化 - Google Patents
配列操作のための改善された系、方法および酵素組成物のエンジニアリングおよび最適化 Download PDFInfo
- Publication number
- JP2018143253A JP2018143253A JP2018119670A JP2018119670A JP2018143253A JP 2018143253 A JP2018143253 A JP 2018143253A JP 2018119670 A JP2018119670 A JP 2018119670A JP 2018119670 A JP2018119670 A JP 2018119670A JP 2018143253 A JP2018143253 A JP 2018143253A
- Authority
- JP
- Japan
- Prior art keywords
- sequence
- cas9
- crispr
- sequences
- rna
- 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.)
- Granted
Links
- 238000000034 method Methods 0.000 title claims abstract description 151
- 239000000203 mixture Substances 0.000 title claims abstract description 53
- 102000004190 Enzymes Human genes 0.000 title abstract description 215
- 108090000790 Enzymes Proteins 0.000 title abstract description 215
- 238000005457 optimization Methods 0.000 title abstract description 14
- 230000001976 improved effect Effects 0.000 title description 12
- 108091033409 CRISPR Proteins 0.000 claims abstract description 344
- 238000010354 CRISPR gene editing Methods 0.000 claims abstract 9
- 108090000623 proteins and genes Proteins 0.000 claims description 213
- 210000004027 cell Anatomy 0.000 claims description 175
- 239000013598 vector Substances 0.000 claims description 143
- 102000040430 polynucleotide Human genes 0.000 claims description 131
- 108091033319 polynucleotide Proteins 0.000 claims description 131
- 239000002157 polynucleotide Substances 0.000 claims description 131
- 230000014509 gene expression Effects 0.000 claims description 119
- 108091032973 (ribonucleotides)n+m Proteins 0.000 claims description 54
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 49
- 241000282414 Homo sapiens Species 0.000 claims description 48
- 125000003729 nucleotide group Chemical group 0.000 claims description 48
- 108020004705 Codon Proteins 0.000 claims description 46
- 239000002773 nucleotide Substances 0.000 claims description 43
- 210000003527 eukaryotic cell Anatomy 0.000 claims description 34
- 108091092236 Chimeric RNA Proteins 0.000 claims description 32
- 201000010099 disease Diseases 0.000 claims description 32
- 238000010362 genome editing Methods 0.000 claims description 28
- 239000013603 viral vector Substances 0.000 claims description 28
- 210000001519 tissue Anatomy 0.000 claims description 26
- 238000000338 in vitro Methods 0.000 claims description 23
- 241000701161 unidentified adenovirus Species 0.000 claims description 22
- 230000030648 nucleus localization Effects 0.000 claims description 17
- 230000002068 genetic effect Effects 0.000 claims description 14
- 230000008569 process Effects 0.000 claims description 13
- 230000009870 specific binding Effects 0.000 claims description 12
- 241000191967 Staphylococcus aureus Species 0.000 claims description 11
- 239000002502 liposome Substances 0.000 claims description 10
- 241000702421 Dependoparvovirus Species 0.000 claims description 8
- 210000001808 exosome Anatomy 0.000 claims description 8
- 210000002569 neuron Anatomy 0.000 claims description 8
- 210000004185 liver Anatomy 0.000 claims description 7
- 239000002105 nanoparticle Substances 0.000 claims description 7
- 241000713666 Lentivirus Species 0.000 claims description 6
- 241001430294 unidentified retrovirus Species 0.000 claims description 6
- 240000004808 Saccharomyces cerevisiae Species 0.000 claims description 5
- 238000011282 treatment Methods 0.000 claims description 5
- 241000700584 Simplexvirus Species 0.000 claims description 4
- 210000004602 germ cell Anatomy 0.000 claims description 4
- 241000206602 Eukaryota Species 0.000 claims description 3
- 210000000496 pancreas Anatomy 0.000 claims description 3
- 210000000130 stem cell Anatomy 0.000 claims description 3
- 210000004369 blood Anatomy 0.000 claims description 2
- 239000008280 blood Substances 0.000 claims description 2
- 210000000988 bone and bone Anatomy 0.000 claims description 2
- 210000004698 lymphocyte Anatomy 0.000 claims description 2
- 210000003205 muscle Anatomy 0.000 claims description 2
- 210000003491 skin Anatomy 0.000 claims description 2
- 210000002980 germ line cell Anatomy 0.000 claims 1
- 230000002265 prevention Effects 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 43
- 230000008685 targeting Effects 0.000 abstract description 17
- 230000008901 benefit Effects 0.000 abstract description 7
- 229940088598 enzyme Drugs 0.000 description 213
- 102000004169 proteins and genes Human genes 0.000 description 95
- 108020005004 Guide RNA Proteins 0.000 description 92
- 235000018102 proteins Nutrition 0.000 description 91
- 235000001014 amino acid Nutrition 0.000 description 87
- 230000035772 mutation Effects 0.000 description 87
- 229940024606 amino acid Drugs 0.000 description 86
- 150000001413 amino acids Chemical class 0.000 description 84
- 108020004414 DNA Proteins 0.000 description 82
- 150000007523 nucleic acids Chemical class 0.000 description 75
- 102000039446 nucleic acids Human genes 0.000 description 64
- 108020004707 nucleic acids Proteins 0.000 description 64
- 230000003197 catalytic effect Effects 0.000 description 49
- 238000003776 cleavage reaction Methods 0.000 description 48
- 230000007017 scission Effects 0.000 description 48
- 230000001105 regulatory effect Effects 0.000 description 46
- 239000000047 product Substances 0.000 description 39
- 108020004999 messenger RNA Proteins 0.000 description 34
- 238000003556 assay Methods 0.000 description 31
- 108010008532 Deoxyribonuclease I Proteins 0.000 description 29
- 102000007260 Deoxyribonuclease I Human genes 0.000 description 29
- 238000012360 testing method Methods 0.000 description 27
- 239000002245 particle Substances 0.000 description 25
- 230000006870 function Effects 0.000 description 24
- 238000001727 in vivo Methods 0.000 description 24
- 239000013612 plasmid Substances 0.000 description 24
- 239000003814 drug Substances 0.000 description 23
- 238000009396 hybridization Methods 0.000 description 23
- 241000700605 Viruses Species 0.000 description 22
- 230000009287 biochemical signal transduction Effects 0.000 description 22
- 230000000295 complement effect Effects 0.000 description 22
- 239000000523 sample Substances 0.000 description 21
- 108091028043 Nucleic acid sequence Proteins 0.000 description 20
- 238000009739 binding Methods 0.000 description 20
- 238000004806 packaging method and process Methods 0.000 description 20
- 108090000765 processed proteins & peptides Proteins 0.000 description 20
- 238000013518 transcription Methods 0.000 description 20
- 230000035897 transcription Effects 0.000 description 20
- 230000027455 binding Effects 0.000 description 19
- 239000013604 expression vector Substances 0.000 description 19
- 238000003780 insertion Methods 0.000 description 19
- 230000037431 insertion Effects 0.000 description 19
- 230000004048 modification Effects 0.000 description 19
- 238000012986 modification Methods 0.000 description 19
- 230000004568 DNA-binding Effects 0.000 description 18
- 229940079593 drug Drugs 0.000 description 18
- 125000006850 spacer group Chemical group 0.000 description 18
- 230000003612 virological effect Effects 0.000 description 18
- 238000011144 upstream manufacturing Methods 0.000 description 17
- 108091026890 Coding region Proteins 0.000 description 16
- -1 Corynebacter Proteins 0.000 description 16
- 241000204031 Mycoplasma Species 0.000 description 16
- 208000035475 disorder Diseases 0.000 description 16
- 230000001939 inductive effect Effects 0.000 description 16
- 238000004519 manufacturing process Methods 0.000 description 16
- 238000006467 substitution reaction Methods 0.000 description 16
- 101710163270 Nuclease Proteins 0.000 description 15
- 239000012634 fragment Substances 0.000 description 15
- 102000004196 processed proteins & peptides Human genes 0.000 description 15
- 239000004055 small Interfering RNA Substances 0.000 description 15
- 101710172824 CRISPR-associated endonuclease Cas9 Proteins 0.000 description 14
- 241000193996 Streptococcus pyogenes Species 0.000 description 14
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 14
- 108020004459 Small interfering RNA Proteins 0.000 description 13
- 241000194017 Streptococcus Species 0.000 description 13
- 230000003321 amplification Effects 0.000 description 13
- 238000002887 multiple sequence alignment Methods 0.000 description 13
- 238000003199 nucleic acid amplification method Methods 0.000 description 13
- 238000004904 shortening Methods 0.000 description 13
- 238000001890 transfection Methods 0.000 description 13
- 241000186660 Lactobacillus Species 0.000 description 12
- 230000015572 biosynthetic process Effects 0.000 description 12
- 238000004422 calculation algorithm Methods 0.000 description 12
- 238000013461 design Methods 0.000 description 12
- 229940039696 lactobacillus Drugs 0.000 description 12
- 229920001184 polypeptide Polymers 0.000 description 12
- 230000010076 replication Effects 0.000 description 12
- 208000011580 syndromic disease Diseases 0.000 description 12
- 238000013081 phylogenetic analysis Methods 0.000 description 11
- 238000004458 analytical method Methods 0.000 description 10
- 230000002950 deficient Effects 0.000 description 10
- 230000005782 double-strand break Effects 0.000 description 10
- 230000004927 fusion Effects 0.000 description 10
- 102000037865 fusion proteins Human genes 0.000 description 10
- 108020001507 fusion proteins Proteins 0.000 description 10
- 239000013607 AAV vector Substances 0.000 description 9
- 241000894006 Bacteria Species 0.000 description 9
- 241000589876 Campylobacter Species 0.000 description 9
- 230000007018 DNA scission Effects 0.000 description 9
- 241000186394 Eubacterium Species 0.000 description 9
- 241000191940 Staphylococcus Species 0.000 description 9
- 241000589886 Treponema Species 0.000 description 9
- 210000004556 brain Anatomy 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 9
- 238000001415 gene therapy Methods 0.000 description 9
- 230000010354 integration Effects 0.000 description 9
- 210000004940 nucleus Anatomy 0.000 description 9
- 108091006107 transcriptional repressors Proteins 0.000 description 9
- 241000606125 Bacteroides Species 0.000 description 8
- 102000053602 DNA Human genes 0.000 description 8
- 241000196324 Embryophyta Species 0.000 description 8
- 108010033040 Histones Proteins 0.000 description 8
- 241000589248 Legionella Species 0.000 description 8
- 208000007764 Legionnaires' Disease Diseases 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 8
- 241000588653 Neisseria Species 0.000 description 8
- 241000194020 Streptococcus thermophilus Species 0.000 description 8
- 238000013459 approach Methods 0.000 description 8
- 230000001580 bacterial effect Effects 0.000 description 8
- 239000000872 buffer Substances 0.000 description 8
- 238000012217 deletion Methods 0.000 description 8
- 230000037430 deletion Effects 0.000 description 8
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 8
- 210000004962 mammalian cell Anatomy 0.000 description 8
- 230000001404 mediated effect Effects 0.000 description 8
- 241000894007 species Species 0.000 description 8
- 241000701022 Cytomegalovirus Species 0.000 description 7
- 241000178967 Filifactor Species 0.000 description 7
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 7
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 7
- 230000005856 abnormality Effects 0.000 description 7
- 238000001514 detection method Methods 0.000 description 7
- 238000005516 engineering process Methods 0.000 description 7
- 239000003623 enhancer Substances 0.000 description 7
- 238000002744 homologous recombination Methods 0.000 description 7
- 230000006801 homologous recombination Effects 0.000 description 7
- 230000001965 increasing effect Effects 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- 231100000419 toxicity Toxicity 0.000 description 7
- 230000001988 toxicity Effects 0.000 description 7
- 108091006106 transcriptional activators Proteins 0.000 description 7
- 241000701447 unidentified baculovirus Species 0.000 description 7
- 102100033647 Activity-regulated cytoskeleton-associated protein Human genes 0.000 description 6
- 241000589941 Azospirillum Species 0.000 description 6
- 108091029865 Exogenous DNA Proteins 0.000 description 6
- 241000589565 Flavobacterium Species 0.000 description 6
- 241000032681 Gluconacetobacter Species 0.000 description 6
- 241000238631 Hexapoda Species 0.000 description 6
- 241000699666 Mus <mouse, genus> Species 0.000 description 6
- 230000002159 abnormal effect Effects 0.000 description 6
- 230000006978 adaptation Effects 0.000 description 6
- 235000004279 alanine Nutrition 0.000 description 6
- 125000000539 amino acid group Chemical group 0.000 description 6
- 230000008859 change Effects 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 6
- 230000010534 mechanism of action Effects 0.000 description 6
- 229920000642 polymer Polymers 0.000 description 6
- 230000001177 retroviral effect Effects 0.000 description 6
- 230000002441 reversible effect Effects 0.000 description 6
- 238000012546 transfer Methods 0.000 description 6
- 230000009261 transgenic effect Effects 0.000 description 6
- 241001634120 Adeno-associated virus - 5 Species 0.000 description 5
- 108700010070 Codon Usage Proteins 0.000 description 5
- 108010037139 Cryptochromes Proteins 0.000 description 5
- 102000052510 DNA-Binding Proteins Human genes 0.000 description 5
- 241000588724 Escherichia coli Species 0.000 description 5
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 5
- 101001048956 Homo sapiens Homeobox protein EMX1 Proteins 0.000 description 5
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 5
- 241000829100 Macaca mulatta polyomavirus 1 Species 0.000 description 5
- 108700040121 Protein Methyltransferases Proteins 0.000 description 5
- 102000055027 Protein Methyltransferases Human genes 0.000 description 5
- 102000018120 Recombinases Human genes 0.000 description 5
- 108010091086 Recombinases Proteins 0.000 description 5
- 108091081062 Repeated sequence (DNA) Proteins 0.000 description 5
- 241000605947 Roseburia Species 0.000 description 5
- 241000949716 Sphaerochaeta Species 0.000 description 5
- 108020004566 Transfer RNA Proteins 0.000 description 5
- 102000008579 Transposases Human genes 0.000 description 5
- 108010020764 Transposases Proteins 0.000 description 5
- 239000002671 adjuvant Substances 0.000 description 5
- 125000003275 alpha amino acid group Chemical group 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 230000034431 double-strand break repair via homologous recombination Effects 0.000 description 5
- 239000000499 gel Substances 0.000 description 5
- 230000036541 health Effects 0.000 description 5
- 229910052739 hydrogen Inorganic materials 0.000 description 5
- 239000001257 hydrogen Substances 0.000 description 5
- 230000003834 intracellular effect Effects 0.000 description 5
- 150000002632 lipids Chemical class 0.000 description 5
- 238000001638 lipofection Methods 0.000 description 5
- 239000011159 matrix material Substances 0.000 description 5
- 230000037361 pathway Effects 0.000 description 5
- 210000001236 prokaryotic cell Anatomy 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 230000002103 transcriptional effect Effects 0.000 description 5
- 241001655883 Adeno-associated virus - 1 Species 0.000 description 4
- 241000702423 Adeno-associated virus - 2 Species 0.000 description 4
- 102100027211 Albumin Human genes 0.000 description 4
- 108010088751 Albumins Proteins 0.000 description 4
- 102100033312 Alpha-2-macroglobulin Human genes 0.000 description 4
- 101710096438 DNA-binding protein Proteins 0.000 description 4
- 108010070675 Glutathione transferase Proteins 0.000 description 4
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
- 102100029100 Hematopoietic prostaglandin D synthase Human genes 0.000 description 4
- 102100023823 Homeobox protein EMX1 Human genes 0.000 description 4
- 241000282412 Homo Species 0.000 description 4
- 101000891092 Homo sapiens TAR DNA-binding protein 43 Proteins 0.000 description 4
- 208000026350 Inborn Genetic disease Diseases 0.000 description 4
- 102000004877 Insulin Human genes 0.000 description 4
- 108090001061 Insulin Proteins 0.000 description 4
- 108060001084 Luciferase Proteins 0.000 description 4
- 239000005089 Luciferase Substances 0.000 description 4
- 206010028980 Neoplasm Diseases 0.000 description 4
- 241000135938 Nitratifractor Species 0.000 description 4
- 108010015078 Pregnancy-Associated alpha 2-Macroglobulins Proteins 0.000 description 4
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 4
- 102100030547 Serotonin N-acetyltransferase Human genes 0.000 description 4
- 101000910045 Streptococcus thermophilus (strain ATCC BAA-491 / LMD-9) CRISPR-associated endonuclease Cas9 2 Proteins 0.000 description 4
- 108010021188 Superoxide Dismutase-1 Proteins 0.000 description 4
- 102100038836 Superoxide dismutase [Cu-Zn] Human genes 0.000 description 4
- 102100040347 TAR DNA-binding protein 43 Human genes 0.000 description 4
- 101710176279 Tubulin beta-2 chain Proteins 0.000 description 4
- 108010073925 Vascular Endothelial Growth Factor B Proteins 0.000 description 4
- 102000009520 Vascular Endothelial Growth Factor C Human genes 0.000 description 4
- 108010073923 Vascular Endothelial Growth Factor C Proteins 0.000 description 4
- 102100038217 Vascular endothelial growth factor B Human genes 0.000 description 4
- 230000004913 activation Effects 0.000 description 4
- 201000008266 amyotrophic lateral sclerosis type 2 Diseases 0.000 description 4
- 239000000427 antigen Substances 0.000 description 4
- 108091007433 antigens Proteins 0.000 description 4
- 102000036639 antigens Human genes 0.000 description 4
- 230000008238 biochemical pathway Effects 0.000 description 4
- 230000008499 blood brain barrier function Effects 0.000 description 4
- 210000001218 blood-brain barrier Anatomy 0.000 description 4
- 238000010367 cloning Methods 0.000 description 4
- 230000009918 complex formation Effects 0.000 description 4
- 238000004590 computer program Methods 0.000 description 4
- 230000001419 dependent effect Effects 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 230000018109 developmental process Effects 0.000 description 4
- 238000004520 electroporation Methods 0.000 description 4
- 230000001973 epigenetic effect Effects 0.000 description 4
- 206010015037 epilepsy Diseases 0.000 description 4
- 208000016361 genetic disease Diseases 0.000 description 4
- 229940125396 insulin Drugs 0.000 description 4
- 208000032799 juvenile amyotrophic lateral sclerosis type 2 Diseases 0.000 description 4
- 239000003446 ligand Substances 0.000 description 4
- 230000004807 localization Effects 0.000 description 4
- 230000011987 methylation Effects 0.000 description 4
- 238000007069 methylation reaction Methods 0.000 description 4
- 239000002679 microRNA Substances 0.000 description 4
- 230000006780 non-homologous end joining Effects 0.000 description 4
- 230000003287 optical effect Effects 0.000 description 4
- 108020001580 protein domains Proteins 0.000 description 4
- 238000003259 recombinant expression Methods 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- 230000011664 signaling Effects 0.000 description 4
- 239000000758 substrate Substances 0.000 description 4
- 238000010361 transduction Methods 0.000 description 4
- 230000026683 transduction Effects 0.000 description 4
- 238000013519 translation Methods 0.000 description 4
- 241001529453 unidentified herpesvirus Species 0.000 description 4
- 238000001262 western blot Methods 0.000 description 4
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 3
- 108020005345 3' Untranslated Regions Proteins 0.000 description 3
- 208000024827 Alzheimer disease Diseases 0.000 description 3
- 206010003591 Ataxia Diseases 0.000 description 3
- 241000195597 Chlamydomonas reinhardtii Species 0.000 description 3
- 101710177611 DNA polymerase II large subunit Proteins 0.000 description 3
- 101710184669 DNA polymerase II small subunit Proteins 0.000 description 3
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 208000023105 Huntington disease Diseases 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- 108020004711 Nucleic Acid Probes Proteins 0.000 description 3
- 108091034117 Oligonucleotide Proteins 0.000 description 3
- 241000283973 Oryctolagus cuniculus Species 0.000 description 3
- 108010043958 Peptoids Proteins 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- 108020004511 Recombinant DNA Proteins 0.000 description 3
- 241000714474 Rous sarcoma virus Species 0.000 description 3
- 108091027544 Subgenomic mRNA Proteins 0.000 description 3
- 206010043189 Telangiectasia Diseases 0.000 description 3
- 108700019146 Transgenes Proteins 0.000 description 3
- 241000700618 Vaccinia virus Species 0.000 description 3
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 3
- 102100039037 Vascular endothelial growth factor A Human genes 0.000 description 3
- 238000009825 accumulation Methods 0.000 description 3
- DZBUGLKDJFMEHC-UHFFFAOYSA-N acridine Chemical compound C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 description 3
- 208000021841 acute erythroid leukemia Diseases 0.000 description 3
- 210000004102 animal cell Anatomy 0.000 description 3
- 230000000692 anti-sense effect Effects 0.000 description 3
- 108010005774 beta-Galactosidase Proteins 0.000 description 3
- 229960002685 biotin Drugs 0.000 description 3
- 239000011616 biotin Substances 0.000 description 3
- 210000000234 capsid Anatomy 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 230000001413 cellular effect Effects 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 238000010205 computational analysis Methods 0.000 description 3
- 238000002716 delivery method Methods 0.000 description 3
- 238000010586 diagram Methods 0.000 description 3
- 238000009826 distribution Methods 0.000 description 3
- 239000000975 dye Substances 0.000 description 3
- 230000002255 enzymatic effect Effects 0.000 description 3
- 210000002950 fibroblast Anatomy 0.000 description 3
- ZXQYGBMAQZUVMI-GCMPRSNUSA-N gamma-cyhalothrin Chemical compound CC1(C)[C@@H](\C=C(/Cl)C(F)(F)F)[C@H]1C(=O)O[C@H](C#N)C1=CC=CC(OC=2C=CC=CC=2)=C1 ZXQYGBMAQZUVMI-GCMPRSNUSA-N 0.000 description 3
- 238000003209 gene knockout Methods 0.000 description 3
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 3
- 230000003308 immunostimulating effect Effects 0.000 description 3
- 230000002779 inactivation Effects 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 238000002372 labelling Methods 0.000 description 3
- 230000000670 limiting effect Effects 0.000 description 3
- 210000001161 mammalian embryo Anatomy 0.000 description 3
- 210000004779 membrane envelope Anatomy 0.000 description 3
- 238000000520 microinjection Methods 0.000 description 3
- 238000010369 molecular cloning Methods 0.000 description 3
- 230000001537 neural effect Effects 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 108091027963 non-coding RNA Proteins 0.000 description 3
- 102000042567 non-coding RNA Human genes 0.000 description 3
- 239000002853 nucleic acid probe Substances 0.000 description 3
- 230000009437 off-target effect Effects 0.000 description 3
- 230000008520 organization Effects 0.000 description 3
- 108010079892 phosphoglycerol kinase Proteins 0.000 description 3
- 229920002401 polyacrylamide Polymers 0.000 description 3
- 230000004481 post-translational protein modification Effects 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 230000006798 recombination Effects 0.000 description 3
- 238000005215 recombination Methods 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 230000008439 repair process Effects 0.000 description 3
- 230000006641 stabilisation Effects 0.000 description 3
- 238000011105 stabilization Methods 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 208000009056 telangiectasis Diseases 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 230000005030 transcription termination Effects 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- KCYOZNARADAZIZ-CWBQGUJCSA-N 2-[(2e,4e,6e,8e,10e,12e,14e)-15-(4,4,7a-trimethyl-2,5,6,7-tetrahydro-1-benzofuran-2-yl)-6,11-dimethylhexadeca-2,4,6,8,10,12,14-heptaen-2-yl]-4,4,7a-trimethyl-2,5,6,7-tetrahydro-1-benzofuran-6-ol Chemical compound O1C2(C)CC(O)CC(C)(C)C2=CC1C(\C)=C\C=C\C(\C)=C\C=C\C=C(/C)\C=C\C=C(/C)C1C=C2C(C)(C)CCCC2(C)O1 KCYOZNARADAZIZ-CWBQGUJCSA-N 0.000 description 2
- WRMNZCZEMHIOCP-UHFFFAOYSA-N 2-phenylethanol Chemical compound OCCC1=CC=CC=C1 WRMNZCZEMHIOCP-UHFFFAOYSA-N 0.000 description 2
- FWBHETKCLVMNFS-UHFFFAOYSA-N 4',6-Diamino-2-phenylindol Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC2=CC=C(C(N)=N)C=C2N1 FWBHETKCLVMNFS-UHFFFAOYSA-N 0.000 description 2
- 102100035923 4-aminobutyrate aminotransferase, mitochondrial Human genes 0.000 description 2
- 101150092476 ABCA1 gene Proteins 0.000 description 2
- 102100024378 AF4/FMR2 family member 2 Human genes 0.000 description 2
- 108700005241 ATP Binding Cassette Transporter 1 Proteins 0.000 description 2
- 102100033092 ATP-binding cassette sub-family G member 8 Human genes 0.000 description 2
- 241000580270 Adeno-associated virus - 4 Species 0.000 description 2
- 241001164825 Adeno-associated virus - 8 Species 0.000 description 2
- 102100024401 Alpha-1D adrenergic receptor Human genes 0.000 description 2
- 108091093088 Amplicon Proteins 0.000 description 2
- 108010043324 Amyloid Precursor Protein Secretases Proteins 0.000 description 2
- 102000002659 Amyloid Precursor Protein Secretases Human genes 0.000 description 2
- 102100032187 Androgen receptor Human genes 0.000 description 2
- 102000000546 Apoferritins Human genes 0.000 description 2
- 108010002084 Apoferritins Proteins 0.000 description 2
- 102100029470 Apolipoprotein E Human genes 0.000 description 2
- 241000203069 Archaea Species 0.000 description 2
- 108010074515 Arylalkylamine N-Acetyltransferase Proteins 0.000 description 2
- 102000007370 Ataxin2 Human genes 0.000 description 2
- 108010032951 Ataxin2 Proteins 0.000 description 2
- 102100026189 Beta-galactosidase Human genes 0.000 description 2
- 208000014644 Brain disease Diseases 0.000 description 2
- 101710155857 C-C motif chemokine 2 Proteins 0.000 description 2
- 108091079001 CRISPR RNA Proteins 0.000 description 2
- 238000010356 CRISPR-Cas9 genome editing Methods 0.000 description 2
- 101000909256 Caldicellulosiruptor bescii (strain ATCC BAA-1888 / DSM 6725 / Z-1320) DNA polymerase I Proteins 0.000 description 2
- 241000589875 Campylobacter jejuni Species 0.000 description 2
- 102100025064 Cellular tumor antigen p53 Human genes 0.000 description 2
- 102000000018 Chemokine CCL2 Human genes 0.000 description 2
- 241000195585 Chlamydomonas Species 0.000 description 2
- 108010035563 Chloramphenicol O-acetyltransferase Proteins 0.000 description 2
- 108010077544 Chromatin Proteins 0.000 description 2
- 108091028732 Concatemer Proteins 0.000 description 2
- 206010010904 Convulsion Diseases 0.000 description 2
- KCYOZNARADAZIZ-PPBBKLJYSA-N Cryptochrome Natural products O[C@@H]1CC(C)(C)C=2[C@@](C)(O[C@H](/C(=C\C=C\C(=C/C=C/C=C(\C=C\C=C(\C)/[C@H]3O[C@@]4(C)C(C(C)(C)CCC4)=C3)/C)\C)/C)C=2)C1 KCYOZNARADAZIZ-PPBBKLJYSA-N 0.000 description 2
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 2
- 206010058314 Dysplasia Diseases 0.000 description 2
- 102000001301 EGF receptor Human genes 0.000 description 2
- 108060006698 EGF receptor Proteins 0.000 description 2
- 108700024394 Exon Proteins 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- 108010032606 Fragile X Mental Retardation Protein Proteins 0.000 description 2
- 102000003869 Frataxin Human genes 0.000 description 2
- 108090000217 Frataxin Proteins 0.000 description 2
- 208000024412 Friedreich ataxia Diseases 0.000 description 2
- 101150106478 GPS1 gene Proteins 0.000 description 2
- 102100028260 Gamma-secretase subunit PEN-2 Human genes 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- 239000004471 Glycine Substances 0.000 description 2
- 108010043121 Green Fluorescent Proteins Proteins 0.000 description 2
- 102000004144 Green Fluorescent Proteins Human genes 0.000 description 2
- HVLSXIKZNLPZJJ-TXZCQADKSA-N HA peptide Chemical compound C([C@@H](C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](C)C(O)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=C(O)C=C1 HVLSXIKZNLPZJJ-TXZCQADKSA-N 0.000 description 2
- 101001000686 Homo sapiens 4-aminobutyrate aminotransferase, mitochondrial Proteins 0.000 description 2
- 101000833172 Homo sapiens AF4/FMR2 family member 2 Proteins 0.000 description 2
- 101000721661 Homo sapiens Cellular tumor antigen p53 Proteins 0.000 description 2
- 101000579663 Homo sapiens Gamma-secretase subunit PEN-2 Proteins 0.000 description 2
- 101000891579 Homo sapiens Microtubule-associated protein tau Proteins 0.000 description 2
- 101001135385 Homo sapiens Prostacyclin synthase Proteins 0.000 description 2
- 101000801643 Homo sapiens Retinal-specific phospholipid-transporting ATPase ABCA4 Proteins 0.000 description 2
- 101000652292 Homo sapiens Serotonin N-acetyltransferase Proteins 0.000 description 2
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 2
- 241000725303 Human immunodeficiency virus Species 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- 102100034349 Integrase Human genes 0.000 description 2
- 102000004388 Interleukin-4 Human genes 0.000 description 2
- 108090000978 Interleukin-4 Proteins 0.000 description 2
- 108020004684 Internal Ribosome Entry Sites Proteins 0.000 description 2
- 108091092195 Intron Proteins 0.000 description 2
- 108090000862 Ion Channels Proteins 0.000 description 2
- 102000004310 Ion Channels Human genes 0.000 description 2
- 102100036600 Kynurenine/alpha-aminoadipate aminotransferase, mitochondrial Human genes 0.000 description 2
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 2
- 208000005870 Lafora disease Diseases 0.000 description 2
- 208000014161 Lafora myoclonic epilepsy Diseases 0.000 description 2
- 241000589242 Legionella pneumophila Species 0.000 description 2
- 208000006136 Leigh Disease Diseases 0.000 description 2
- 208000017507 Leigh syndrome Diseases 0.000 description 2
- 208000009625 Lesch-Nyhan syndrome Diseases 0.000 description 2
- 241000282560 Macaca mulatta Species 0.000 description 2
- 101710175625 Maltose/maltodextrin-binding periplasmic protein Proteins 0.000 description 2
- 208000036626 Mental retardation Diseases 0.000 description 2
- 108700011259 MicroRNAs Proteins 0.000 description 2
- 102100040243 Microtubule-associated protein tau Human genes 0.000 description 2
- 241000714177 Murine leukemia virus Species 0.000 description 2
- 101100219625 Mus musculus Casd1 gene Proteins 0.000 description 2
- 108010052185 Myotonin-Protein Kinase Proteins 0.000 description 2
- 102100022437 Myotonin-protein kinase Human genes 0.000 description 2
- 102100028719 NEDD8-activating enzyme E1 catalytic subunit Human genes 0.000 description 2
- 241000588654 Neisseria cinerea Species 0.000 description 2
- 208000012902 Nervous system disease Diseases 0.000 description 2
- 108010040718 Neurokinin-1 Receptors Proteins 0.000 description 2
- 208000025966 Neurological disease Diseases 0.000 description 2
- 208000002537 Neuronal Ceroid-Lipofuscinoses Diseases 0.000 description 2
- 102100022397 Nitric oxide synthase, brain Human genes 0.000 description 2
- 108091092724 Noncoding DNA Proteins 0.000 description 2
- 102000002488 Nucleoplasmin Human genes 0.000 description 2
- 108700020796 Oncogene Proteins 0.000 description 2
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 2
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 2
- 208000018737 Parkinson disease Diseases 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 102100033616 Phospholipid-transporting ATPase ABCA1 Human genes 0.000 description 2
- 102100022033 Presenilin-1 Human genes 0.000 description 2
- 102100022036 Presenilin-2 Human genes 0.000 description 2
- 102000029797 Prion Human genes 0.000 description 2
- 108091000054 Prion Proteins 0.000 description 2
- ZTHYODDOHIVTJV-UHFFFAOYSA-N Propyl gallate Chemical compound CCCOC(=O)C1=CC(O)=C(O)C(O)=C1 ZTHYODDOHIVTJV-UHFFFAOYSA-N 0.000 description 2
- 102100033075 Prostacyclin synthase Human genes 0.000 description 2
- 102100035703 Prostatic acid phosphatase Human genes 0.000 description 2
- 101000902592 Pyrococcus furiosus (strain ATCC 43587 / DSM 3638 / JCM 8422 / Vc1) DNA polymerase Proteins 0.000 description 2
- 102100038188 RNA binding protein fox-1 homolog 1 Human genes 0.000 description 2
- 101100273635 Rattus norvegicus Ccn5 gene Proteins 0.000 description 2
- 108700008625 Reporter Genes Proteins 0.000 description 2
- 206010039491 Sarcoma Diseases 0.000 description 2
- 241000713311 Simian immunodeficiency virus Species 0.000 description 2
- 108091027967 Small hairpin RNA Proteins 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 102000005157 Somatostatin Human genes 0.000 description 2
- 108010056088 Somatostatin Proteins 0.000 description 2
- 241000295644 Staphylococcaceae Species 0.000 description 2
- 241000187747 Streptomyces Species 0.000 description 2
- 102100037346 Substance-P receptor Human genes 0.000 description 2
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 description 2
- 102000001435 Synapsin Human genes 0.000 description 2
- 108050009621 Synapsin Proteins 0.000 description 2
- 102100023532 Synaptic functional regulator FMR1 Human genes 0.000 description 2
- 241000186339 Thermoanaerobacter Species 0.000 description 2
- 102100036407 Thioredoxin Human genes 0.000 description 2
- 208000035317 Total hypoxanthine-guanine phosphoribosyl transferase deficiency Diseases 0.000 description 2
- 108091028113 Trans-activating crRNA Proteins 0.000 description 2
- 241000589892 Treponema denticola Species 0.000 description 2
- 102100037160 Ubiquitin-like modifier-activating enzyme 1 Human genes 0.000 description 2
- 101710191412 Ubiquitin-like modifier-activating enzyme 1 Proteins 0.000 description 2
- 102100039066 Very low-density lipoprotein receptor Human genes 0.000 description 2
- 108010091383 Xanthine dehydrogenase Proteins 0.000 description 2
- 102000005773 Xanthine dehydrogenase Human genes 0.000 description 2
- 108010093894 Xanthine oxidase Proteins 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
- 230000021736 acetylation Effects 0.000 description 2
- 238000006640 acetylation reaction Methods 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 239000012190 activator Substances 0.000 description 2
- 108020004102 alpha-1 Adrenergic Receptor Proteins 0.000 description 2
- 108020004101 alpha-2 Adrenergic Receptor Proteins 0.000 description 2
- 102000030484 alpha-2 Adrenergic Receptor Human genes 0.000 description 2
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 2
- 108010080146 androgen receptors Proteins 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 210000004436 artificial bacterial chromosome Anatomy 0.000 description 2
- 210000001106 artificial yeast chromosome Anatomy 0.000 description 2
- 229940009098 aspartate Drugs 0.000 description 2
- KCYOZNARADAZIZ-XZOHMNSDSA-N beta-cryptochrome Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C1OC2(C)CC(O)CC(C)(C)C2=C1)C=CC=C(/C)C3OC4(C)CCCC(C)(C)C4=C3 KCYOZNARADAZIZ-XZOHMNSDSA-N 0.000 description 2
- 230000002146 bilateral effect Effects 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 230000008827 biological function Effects 0.000 description 2
- 239000012472 biological sample Substances 0.000 description 2
- 108091005948 blue fluorescent proteins Proteins 0.000 description 2
- 210000004958 brain cell Anatomy 0.000 description 2
- 210000004899 c-terminal region Anatomy 0.000 description 2
- 239000001506 calcium phosphate Substances 0.000 description 2
- 229910000389 calcium phosphate Inorganic materials 0.000 description 2
- 235000011010 calcium phosphates Nutrition 0.000 description 2
- 238000004364 calculation method Methods 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 101150055766 cat gene Proteins 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 108020001778 catalytic domains Proteins 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- 210000003483 chromatin Anatomy 0.000 description 2
- 230000002759 chromosomal effect Effects 0.000 description 2
- 210000000349 chromosome Anatomy 0.000 description 2
- 230000021615 conjugation Effects 0.000 description 2
- 238000012258 culturing Methods 0.000 description 2
- 108010082025 cyan fluorescent protein Proteins 0.000 description 2
- 210000000805 cytoplasm Anatomy 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 238000012350 deep sequencing Methods 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- 238000012377 drug delivery Methods 0.000 description 2
- 238000007877 drug screening Methods 0.000 description 2
- 239000012636 effector Substances 0.000 description 2
- CTSPAMFJBXKSOY-UHFFFAOYSA-N ellipticine Chemical compound N1=CC=C2C(C)=C(NC=3C4=CC=CC=3)C4=C(C)C2=C1 CTSPAMFJBXKSOY-UHFFFAOYSA-N 0.000 description 2
- 210000002889 endothelial cell Anatomy 0.000 description 2
- CBOQJANXLMLOSS-UHFFFAOYSA-N ethyl vanillin Chemical compound CCOC1=CC(C=O)=CC=C1O CBOQJANXLMLOSS-UHFFFAOYSA-N 0.000 description 2
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 230000007614 genetic variation Effects 0.000 description 2
- 238000012268 genome sequencing Methods 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 230000013595 glycosylation Effects 0.000 description 2
- 238000006206 glycosylation reaction Methods 0.000 description 2
- 229910052737 gold Inorganic materials 0.000 description 2
- 239000010931 gold Substances 0.000 description 2
- 239000005090 green fluorescent protein Substances 0.000 description 2
- 210000005003 heart tissue Anatomy 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 238000001114 immunoprecipitation Methods 0.000 description 2
- 238000000126 in silico method Methods 0.000 description 2
- 238000010348 incorporation Methods 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 239000000138 intercalating agent Substances 0.000 description 2
- 229940028885 interleukin-4 Drugs 0.000 description 2
- 229940115932 legionella pneumophila Drugs 0.000 description 2
- 230000029226 lipidation Effects 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 208000002780 macular degeneration Diseases 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 108091070501 miRNA Proteins 0.000 description 2
- 239000011707 mineral Substances 0.000 description 2
- 235000010755 mineral Nutrition 0.000 description 2
- 102000035118 modified proteins Human genes 0.000 description 2
- 108091005573 modified proteins Proteins 0.000 description 2
- 230000009826 neoplastic cell growth Effects 0.000 description 2
- 108060005597 nucleoplasmin Proteins 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 229960003104 ornithine Drugs 0.000 description 2
- 230000036961 partial effect Effects 0.000 description 2
- 230000008506 pathogenesis Effects 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 230000026731 phosphorylation Effects 0.000 description 2
- 238000006366 phosphorylation reaction Methods 0.000 description 2
- 238000004393 prognosis Methods 0.000 description 2
- 235000004252 protein component Nutrition 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 230000003252 repetitive effect Effects 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 238000005070 sampling Methods 0.000 description 2
- 201000000980 schizophrenia Diseases 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 238000002864 sequence alignment Methods 0.000 description 2
- 230000019491 signal transduction Effects 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- NHXLMOGPVYXJNR-ATOGVRKGSA-N somatostatin Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CSSC[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N1)[C@@H](C)O)NC(=O)CNC(=O)[C@H](C)N)C(O)=O)=O)[C@H](O)C)C1=CC=CC=C1 NHXLMOGPVYXJNR-ATOGVRKGSA-N 0.000 description 2
- 229960000553 somatostatin Drugs 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- WWJZWCUNLNYYAU-UHFFFAOYSA-N temephos Chemical compound C1=CC(OP(=S)(OC)OC)=CC=C1SC1=CC=C(OP(=S)(OC)OC)C=C1 WWJZWCUNLNYYAU-UHFFFAOYSA-N 0.000 description 2
- 108060008226 thioredoxin Proteins 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- 230000005945 translocation Effects 0.000 description 2
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 2
- 230000010415 tropism Effects 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- 210000002845 virion Anatomy 0.000 description 2
- 239000000277 virosome Substances 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 108091005957 yellow fluorescent proteins Proteins 0.000 description 2
- OPCHFPHZPIURNA-MFERNQICSA-N (2s)-2,5-bis(3-aminopropylamino)-n-[2-(dioctadecylamino)acetyl]pentanamide Chemical compound CCCCCCCCCCCCCCCCCCN(CC(=O)NC(=O)[C@H](CCCNCCCN)NCCCN)CCCCCCCCCCCCCCCCCC OPCHFPHZPIURNA-MFERNQICSA-N 0.000 description 1
- IYKLZBIWFXPUCS-VIFPVBQESA-N (2s)-2-(naphthalen-1-ylamino)propanoic acid Chemical compound C1=CC=C2C(N[C@@H](C)C(O)=O)=CC=CC2=C1 IYKLZBIWFXPUCS-VIFPVBQESA-N 0.000 description 1
- CNMAQBJBWQQZFZ-LURJTMIESA-N (2s)-2-(pyridin-2-ylamino)propanoic acid Chemical compound OC(=O)[C@H](C)NC1=CC=CC=N1 CNMAQBJBWQQZFZ-LURJTMIESA-N 0.000 description 1
- WHTVZRBIWZFKQO-AWEZNQCLSA-N (S)-chloroquine Chemical compound ClC1=CC=C2C(N[C@@H](C)CCCN(CC)CC)=CC=NC2=C1 WHTVZRBIWZFKQO-AWEZNQCLSA-N 0.000 description 1
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- LKSDEJBJXXZASB-WCCKRBBISA-N 2,2-diaminobutanoic acid;(2s)-2,5-diaminopentanoic acid Chemical compound CCC(N)(N)C(O)=O.NCCC[C@H](N)C(O)=O LKSDEJBJXXZASB-WCCKRBBISA-N 0.000 description 1
- NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 1
- CHHHXKFHOYLYRE-UHFFFAOYSA-M 2,4-Hexadienoic acid, potassium salt (1:1), (2E,4E)- Chemical compound [K+].CC=CC=CC([O-])=O CHHHXKFHOYLYRE-UHFFFAOYSA-M 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- WTOFYLAWDLQMBZ-UHFFFAOYSA-N 2-azaniumyl-3-thiophen-2-ylpropanoate Chemical compound OC(=O)C(N)CC1=CC=CS1 WTOFYLAWDLQMBZ-UHFFFAOYSA-N 0.000 description 1
- KKAJSJJFBSOMGS-UHFFFAOYSA-N 3,6-diamino-10-methylacridinium chloride Chemical compound [Cl-].C1=C(N)C=C2[N+](C)=C(C=C(N)C=C3)C3=CC2=C1 KKAJSJJFBSOMGS-UHFFFAOYSA-N 0.000 description 1
- GOLORTLGFDVFDW-UHFFFAOYSA-N 3-(1h-benzimidazol-2-yl)-7-(diethylamino)chromen-2-one Chemical compound C1=CC=C2NC(C3=CC4=CC=C(C=C4OC3=O)N(CC)CC)=NC2=C1 GOLORTLGFDVFDW-UHFFFAOYSA-N 0.000 description 1
- WXNZTHHGJRFXKQ-UHFFFAOYSA-N 4-chlorophenol Chemical compound OC1=CC=C(Cl)C=C1 WXNZTHHGJRFXKQ-UHFFFAOYSA-N 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 102100024959 5-hydroxytryptamine receptor 2C Human genes 0.000 description 1
- STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 description 1
- 101150020052 AADAT gene Proteins 0.000 description 1
- 108091022885 ADAM Proteins 0.000 description 1
- 102000017904 ADRA2C Human genes 0.000 description 1
- 101150037123 APOE gene Proteins 0.000 description 1
- 102100036618 ATP-binding cassette sub-family A member 13 Human genes 0.000 description 1
- 102100033618 ATP-binding cassette sub-family A member 2 Human genes 0.000 description 1
- 102100024643 ATP-binding cassette sub-family D member 1 Human genes 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 208000034012 Acid sphingomyelinase deficiency Diseases 0.000 description 1
- 241000589291 Acinetobacter Species 0.000 description 1
- 241001502050 Acis Species 0.000 description 1
- 102100036732 Actin, aortic smooth muscle Human genes 0.000 description 1
- 102100022900 Actin, cytoplasmic 1 Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 102000008161 Adenosine A3 Receptor Human genes 0.000 description 1
- 108010060261 Adenosine A3 Receptor Proteins 0.000 description 1
- 102100036006 Adenosine receptor A3 Human genes 0.000 description 1
- 201000011452 Adrenoleukodystrophy Diseases 0.000 description 1
- 241000567147 Aeropyrum Species 0.000 description 1
- 101150029691 Aff2 gene Proteins 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 208000011403 Alexander disease Diseases 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- 208000023434 Alpers-Huttenlocher syndrome Diseases 0.000 description 1
- 102100035028 Alpha-L-iduronidase Human genes 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 208000030894 Alpha-N-acetylgalactosaminidase deficiency type 1 Diseases 0.000 description 1
- 102100023635 Alpha-fetoprotein Human genes 0.000 description 1
- 102100026882 Alpha-synuclein Human genes 0.000 description 1
- 208000026833 Alzheimer disease 4 Diseases 0.000 description 1
- 208000031277 Amaurotic familial idiocy Diseases 0.000 description 1
- 102000013455 Amyloid beta-Peptides Human genes 0.000 description 1
- 108010090849 Amyloid beta-Peptides Proteins 0.000 description 1
- 241000192542 Anabaena Species 0.000 description 1
- 208000009575 Angelman syndrome Diseases 0.000 description 1
- 108010048154 Angiopoietin-1 Proteins 0.000 description 1
- 102000009088 Angiopoietin-1 Human genes 0.000 description 1
- 102100034594 Angiopoietin-1 Human genes 0.000 description 1
- 101710095339 Apolipoprotein E Proteins 0.000 description 1
- 241000207208 Aquifex Species 0.000 description 1
- 241000219195 Arabidopsis thaliana Species 0.000 description 1
- 241000205046 Archaeoglobus Species 0.000 description 1
- 102000014461 Ataxins Human genes 0.000 description 1
- 108010078286 Ataxins Proteins 0.000 description 1
- 206010003805 Autism Diseases 0.000 description 1
- 208000020706 Autistic disease Diseases 0.000 description 1
- 208000001992 Autosomal Dominant Optic Atrophy Diseases 0.000 description 1
- 108090001008 Avidin Proteins 0.000 description 1
- 241000193830 Bacillus <bacterium> Species 0.000 description 1
- 108700003860 Bacterial Genes Proteins 0.000 description 1
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
- 206010048409 Brain malformation Diseases 0.000 description 1
- 102000004219 Brain-derived neurotrophic factor Human genes 0.000 description 1
- 108090000715 Brain-derived neurotrophic factor Proteins 0.000 description 1
- 208000010482 CADASIL Diseases 0.000 description 1
- 108091008927 CC chemokine receptors Proteins 0.000 description 1
- 101150052909 CCL2 gene Proteins 0.000 description 1
- 102000005674 CCR Receptors Human genes 0.000 description 1
- 101150083327 CCR2 gene Proteins 0.000 description 1
- 101150017501 CCR5 gene Proteins 0.000 description 1
- 101150018129 CSF2 gene Proteins 0.000 description 1
- 101150069031 CSN2 gene Proteins 0.000 description 1
- 101150023944 CXCR5 gene Proteins 0.000 description 1
- 102000004657 Calcium-Calmodulin-Dependent Protein Kinase Type 2 Human genes 0.000 description 1
- 108010003721 Calcium-Calmodulin-Dependent Protein Kinase Type 2 Proteins 0.000 description 1
- 240000001432 Calendula officinalis Species 0.000 description 1
- 235000005881 Calendula officinalis Nutrition 0.000 description 1
- 208000022526 Canavan disease Diseases 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 102000014914 Carrier Proteins Human genes 0.000 description 1
- 108090000994 Catalytic RNA Proteins 0.000 description 1
- 102000053642 Catalytic RNA Human genes 0.000 description 1
- 108090000712 Cathepsin B Proteins 0.000 description 1
- 102000004225 Cathepsin B Human genes 0.000 description 1
- 102100021633 Cathepsin B Human genes 0.000 description 1
- 108090000625 Cathepsin K Proteins 0.000 description 1
- 102000004171 Cathepsin K Human genes 0.000 description 1
- 102100024940 Cathepsin K Human genes 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 206010008025 Cerebellar ataxia Diseases 0.000 description 1
- 208000033221 Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy Diseases 0.000 description 1
- 208000033935 Cerebral autosomal dominant arteriopathy-subcortical infarcts-leukoencephalopathy Diseases 0.000 description 1
- 206010053684 Cerebrohepatorenal syndrome Diseases 0.000 description 1
- 102000019034 Chemokines Human genes 0.000 description 1
- 108010012236 Chemokines Proteins 0.000 description 1
- 241000191366 Chlorobium Species 0.000 description 1
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 1
- 241000588881 Chromobacterium Species 0.000 description 1
- 241000207199 Citrus Species 0.000 description 1
- 241000193403 Clostridium Species 0.000 description 1
- 101100007328 Cocos nucifera COS-1 gene Proteins 0.000 description 1
- 102000002734 Collagen Type VI Human genes 0.000 description 1
- 108010043741 Collagen Type VI Proteins 0.000 description 1
- 102100033601 Collagen alpha-1(I) chain Human genes 0.000 description 1
- 206010010099 Combined immunodeficiency Diseases 0.000 description 1
- 102100027826 Complexin-1 Human genes 0.000 description 1
- 208000037141 Congenital muscular dystrophy, Fukuyama type Diseases 0.000 description 1
- 102100040501 Contactin-associated protein 1 Human genes 0.000 description 1
- 101710196304 Contactin-associated protein 1 Proteins 0.000 description 1
- 102000020856 Copper Transport Proteins Human genes 0.000 description 1
- 108091004554 Copper Transport Proteins Proteins 0.000 description 1
- 102000012437 Copper-Transporting ATPases Human genes 0.000 description 1
- 108010022637 Copper-Transporting ATPases Proteins 0.000 description 1
- 241000186216 Corynebacterium Species 0.000 description 1
- 241000700626 Cowpox virus Species 0.000 description 1
- 108091029523 CpG island Proteins 0.000 description 1
- 241000195493 Cryptophyta Species 0.000 description 1
- 101150074775 Csf1 gene Proteins 0.000 description 1
- 108010052832 Cytochromes Proteins 0.000 description 1
- 102000018832 Cytochromes Human genes 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 108010017826 DNA Polymerase I Proteins 0.000 description 1
- 102000004594 DNA Polymerase I Human genes 0.000 description 1
- 230000004544 DNA amplification Effects 0.000 description 1
- 101710135281 DNA polymerase III PolC-type Proteins 0.000 description 1
- 102100036951 DNA polymerase subunit gamma-1 Human genes 0.000 description 1
- 238000001712 DNA sequencing Methods 0.000 description 1
- 241000450599 DNA viruses Species 0.000 description 1
- 108700020911 DNA-Binding Proteins Proteins 0.000 description 1
- WEAHRLBPCANXCN-UHFFFAOYSA-N Daunomycin Natural products CCC1(O)CC(OC2CC(N)C(O)C(C)O2)c3cc4C(=O)c5c(OC)cccc5C(=O)c4c(O)c3C1 WEAHRLBPCANXCN-UHFFFAOYSA-N 0.000 description 1
- 206010012289 Dementia Diseases 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 208000004986 Diffuse Cerebral Sclerosis of Schilder Diseases 0.000 description 1
- SHIBSTMRCDJXLN-UHFFFAOYSA-N Digoxigenin Natural products C1CC(C2C(C3(C)CCC(O)CC3CC2)CC2O)(O)C2(C)C1C1=CC(=O)OC1 SHIBSTMRCDJXLN-UHFFFAOYSA-N 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 102100022825 Disintegrin and metalloproteinase domain-containing protein 22 Human genes 0.000 description 1
- 102100022273 Disrupted in schizophrenia 1 protein Human genes 0.000 description 1
- 241000004297 Draba Species 0.000 description 1
- 239000001692 EU approved anti-caking agent Substances 0.000 description 1
- 241000611421 Elia Species 0.000 description 1
- 102100031780 Endonuclease Human genes 0.000 description 1
- 108010042407 Endonucleases Proteins 0.000 description 1
- 108010013369 Enteropeptidase Proteins 0.000 description 1
- 102100029727 Enteropeptidase Human genes 0.000 description 1
- 101710091045 Envelope protein Proteins 0.000 description 1
- 206010014989 Epidermolysis bullosa Diseases 0.000 description 1
- YQYJSBFKSSDGFO-UHFFFAOYSA-N Epihygromycin Natural products OC1C(O)C(C(=O)C)OC1OC(C(=C1)O)=CC=C1C=C(C)C(=O)NC1C(O)C(O)C2OCOC2C1O YQYJSBFKSSDGFO-UHFFFAOYSA-N 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 241000588698 Erwinia Species 0.000 description 1
- 102100035549 Eukaryotic translation initiation factor 2 subunit 1 Human genes 0.000 description 1
- 101710151743 Eukaryotic translation initiation factor 2 subunit 1 Proteins 0.000 description 1
- 101150107205 FCGR2 gene Proteins 0.000 description 1
- 101150061264 FXR1 gene Proteins 0.000 description 1
- 208000024720 Fabry Disease Diseases 0.000 description 1
- 108010074860 Factor Xa Proteins 0.000 description 1
- 101150114401 Fcer1g gene Proteins 0.000 description 1
- 241001282092 Filifactor alocis Species 0.000 description 1
- 102100036334 Fragile X mental retardation syndrome-related protein 1 Human genes 0.000 description 1
- 102100036336 Fragile X mental retardation syndrome-related protein 2 Human genes 0.000 description 1
- 208000001914 Fragile X syndrome Diseases 0.000 description 1
- 201000006813 Fukuyama congenital muscular dystrophy Diseases 0.000 description 1
- 241000605909 Fusobacterium Species 0.000 description 1
- 102000004300 GABA-A Receptors Human genes 0.000 description 1
- 108090000839 GABA-A Receptors Proteins 0.000 description 1
- 101150014889 Gad1 gene Proteins 0.000 description 1
- 208000017462 Galactosialidosis Diseases 0.000 description 1
- 102100039556 Galectin-4 Human genes 0.000 description 1
- 102100033713 Gamma-secretase subunit APH-1B Human genes 0.000 description 1
- 208000015872 Gaucher disease Diseases 0.000 description 1
- 206010064571 Gene mutation Diseases 0.000 description 1
- 108700028146 Genetic Enhancer Elements Proteins 0.000 description 1
- 108700007698 Genetic Terminator Regions Proteins 0.000 description 1
- 208000031448 Genomic Instability Diseases 0.000 description 1
- 241001135750 Geobacter Species 0.000 description 1
- 241000713813 Gibbon ape leukemia virus Species 0.000 description 1
- 208000010055 Globoid Cell Leukodystrophy Diseases 0.000 description 1
- 108010060309 Glucuronidase Proteins 0.000 description 1
- 102000053187 Glucuronidase Human genes 0.000 description 1
- 102100035902 Glutamate decarboxylase 1 Human genes 0.000 description 1
- 102100035857 Glutamate decarboxylase 2 Human genes 0.000 description 1
- 229920002527 Glycogen Polymers 0.000 description 1
- 108010051975 Glycogen Synthase Kinase 3 beta Proteins 0.000 description 1
- 208000032007 Glycogen storage disease due to acid maltase deficiency Diseases 0.000 description 1
- 206010053185 Glycogen storage disease type II Diseases 0.000 description 1
- 102100022975 Glycogen synthase kinase-3 alpha Human genes 0.000 description 1
- 102100038104 Glycogen synthase kinase-3 beta Human genes 0.000 description 1
- ZIXGXMMUKPLXBB-UHFFFAOYSA-N Guatambuinine Natural products N1C2=CC=CC=C2C2=C1C(C)=C1C=CN=C(C)C1=C2 ZIXGXMMUKPLXBB-UHFFFAOYSA-N 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 108050008753 HNH endonucleases Proteins 0.000 description 1
- 102000000310 HNH endonucleases Human genes 0.000 description 1
- 241000204991 Haloferax Species 0.000 description 1
- 102100021519 Hemoglobin subunit beta Human genes 0.000 description 1
- 108091005904 Hemoglobin subunit beta Proteins 0.000 description 1
- 208000036066 Hemophagocytic Lymphohistiocytosis Diseases 0.000 description 1
- 101001023784 Heteractis crispa GFP-like non-fluorescent chromoprotein Proteins 0.000 description 1
- 108091027305 Heteroduplex Proteins 0.000 description 1
- 208000032672 Histiocytosis haematophagic Diseases 0.000 description 1
- 101000761348 Homo sapiens 5-hydroxytryptamine receptor 2C Proteins 0.000 description 1
- 101000929660 Homo sapiens ATP-binding cassette sub-family A member 13 Proteins 0.000 description 1
- 101000801645 Homo sapiens ATP-binding cassette sub-family A member 2 Proteins 0.000 description 1
- 101000800430 Homo sapiens ATP-binding cassette sub-family G member 8 Proteins 0.000 description 1
- 101000929319 Homo sapiens Actin, aortic smooth muscle Proteins 0.000 description 1
- 101000783645 Homo sapiens Adenosine receptor A3 Proteins 0.000 description 1
- 101000775498 Homo sapiens Adenylate cyclase type 10 Proteins 0.000 description 1
- 101000720032 Homo sapiens Alpha-2C adrenergic receptor Proteins 0.000 description 1
- 101001019502 Homo sapiens Alpha-L-iduronidase Proteins 0.000 description 1
- 101000924552 Homo sapiens Angiopoietin-1 Proteins 0.000 description 1
- 101000898449 Homo sapiens Cathepsin B Proteins 0.000 description 1
- 101000761509 Homo sapiens Cathepsin K Proteins 0.000 description 1
- 101000859600 Homo sapiens Complexin-1 Proteins 0.000 description 1
- 101000804964 Homo sapiens DNA polymerase subunit gamma-1 Proteins 0.000 description 1
- 101000756722 Homo sapiens Disintegrin and metalloproteinase domain-containing protein 22 Proteins 0.000 description 1
- 101000902072 Homo sapiens Disrupted in schizophrenia 1 protein Proteins 0.000 description 1
- 101000619542 Homo sapiens E3 ubiquitin-protein ligase parkin Proteins 0.000 description 1
- 101100335685 Homo sapiens FXR2 gene Proteins 0.000 description 1
- 101000930945 Homo sapiens Fragile X mental retardation syndrome-related protein 1 Proteins 0.000 description 1
- 101000930952 Homo sapiens Fragile X mental retardation syndrome-related protein 2 Proteins 0.000 description 1
- 101000608765 Homo sapiens Galectin-4 Proteins 0.000 description 1
- 101000733778 Homo sapiens Gamma-secretase subunit APH-1B Proteins 0.000 description 1
- 101000873786 Homo sapiens Glutamate decarboxylase 2 Proteins 0.000 description 1
- 101000903717 Homo sapiens Glycogen synthase kinase-3 alpha Proteins 0.000 description 1
- 101000843809 Homo sapiens Hydroxycarboxylic acid receptor 2 Proteins 0.000 description 1
- 101000852815 Homo sapiens Insulin receptor Proteins 0.000 description 1
- 101000929733 Homo sapiens Kynurenine/alpha-aminoadipate aminotransferase, mitochondrial Proteins 0.000 description 1
- 101000917826 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor II-a Proteins 0.000 description 1
- 101000917824 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor II-b Proteins 0.000 description 1
- 101001057159 Homo sapiens Melanoma-associated antigen C3 Proteins 0.000 description 1
- 101000615488 Homo sapiens Methyl-CpG-binding domain protein 2 Proteins 0.000 description 1
- 101000982010 Homo sapiens Myelin proteolipid protein Proteins 0.000 description 1
- 101000837517 Homo sapiens NEDD8-activating enzyme E1 catalytic subunit Proteins 0.000 description 1
- 101001108436 Homo sapiens Neurexin-1 Proteins 0.000 description 1
- 101001108433 Homo sapiens Neurexin-1-beta Proteins 0.000 description 1
- 101000974009 Homo sapiens Nitric oxide synthase, brain Proteins 0.000 description 1
- 101001109698 Homo sapiens Nuclear receptor subfamily 4 group A member 2 Proteins 0.000 description 1
- 101000595929 Homo sapiens POLG alternative reading frame Proteins 0.000 description 1
- 101000801640 Homo sapiens Phospholipid-transporting ATPase ABCA3 Proteins 0.000 description 1
- 101001064282 Homo sapiens Platelet-activating factor acetylhydrolase IB subunit beta Proteins 0.000 description 1
- 101000617536 Homo sapiens Presenilin-1 Proteins 0.000 description 1
- 101000617546 Homo sapiens Presenilin-2 Proteins 0.000 description 1
- 101001001272 Homo sapiens Prostatic acid phosphatase Proteins 0.000 description 1
- 101000600434 Homo sapiens Putative uncharacterized protein encoded by MIR7-3HG Proteins 0.000 description 1
- 101000665449 Homo sapiens RNA binding protein fox-1 homolog 1 Proteins 0.000 description 1
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 1
- 101000738771 Homo sapiens Receptor-type tyrosine-protein phosphatase C Proteins 0.000 description 1
- 101000605835 Homo sapiens Serine/threonine-protein kinase PINK1, mitochondrial Proteins 0.000 description 1
- 101000821100 Homo sapiens Synapsin-1 Proteins 0.000 description 1
- 101000575685 Homo sapiens Synembryn-B Proteins 0.000 description 1
- 101000892398 Homo sapiens Tryptophan 2,3-dioxygenase Proteins 0.000 description 1
- 101000830742 Homo sapiens Tryptophan 5-hydroxylase 1 Proteins 0.000 description 1
- 101000851865 Homo sapiens Tryptophan 5-hydroxylase 2 Proteins 0.000 description 1
- 101000742373 Homo sapiens Vesicular inhibitory amino acid transporter Proteins 0.000 description 1
- 101001074035 Homo sapiens Zinc finger protein GLI2 Proteins 0.000 description 1
- 206010020460 Human T-cell lymphotropic virus type I infection Diseases 0.000 description 1
- 241000714260 Human T-lymphotropic virus 1 Species 0.000 description 1
- 241000701109 Human adenovirus 2 Species 0.000 description 1
- 208000025500 Hutchinson-Gilford progeria syndrome Diseases 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 102100030643 Hydroxycarboxylic acid receptor 2 Human genes 0.000 description 1
- 108010073807 IgG Receptors Proteins 0.000 description 1
- 102000009490 IgG Receptors Human genes 0.000 description 1
- 206010061598 Immunodeficiency Diseases 0.000 description 1
- 208000029462 Immunodeficiency disease Diseases 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 208000028547 Inborn Urea Cycle disease Diseases 0.000 description 1
- 102000000589 Interleukin-1 Human genes 0.000 description 1
- 108010002352 Interleukin-1 Proteins 0.000 description 1
- 208000028226 Krabbe disease Diseases 0.000 description 1
- ZGUNAGUHMKGQNY-ZETCQYMHSA-N L-alpha-phenylglycine zwitterion Chemical compound OC(=O)[C@@H](N)C1=CC=CC=C1 ZGUNAGUHMKGQNY-ZETCQYMHSA-N 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- LRQKBLKVPFOOQJ-YFKPBYRVSA-N L-norleucine Chemical compound CCCC[C@H]([NH3+])C([O-])=O LRQKBLKVPFOOQJ-YFKPBYRVSA-N 0.000 description 1
- 208000012383 LAMA2-related muscular dystrophy Diseases 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 208000031905 Laminin subunit alpha 2-related muscular dystrophy Diseases 0.000 description 1
- 102100022745 Laminin subunit alpha-2 Human genes 0.000 description 1
- 101710128836 Large T antigen Proteins 0.000 description 1
- 108010020246 Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 Proteins 0.000 description 1
- 102100032693 Leucine-rich repeat serine/threonine-protein kinase 2 Human genes 0.000 description 1
- 239000000232 Lipid Bilayer Substances 0.000 description 1
- 241000186781 Listeria Species 0.000 description 1
- 102100029204 Low affinity immunoglobulin gamma Fc region receptor II-a Human genes 0.000 description 1
- 108090000856 Lyases Proteins 0.000 description 1
- 102000004317 Lyases Human genes 0.000 description 1
- 208000003221 Lysosomal acid lipase deficiency Diseases 0.000 description 1
- 102100033448 Lysosomal alpha-glucosidase Human genes 0.000 description 1
- 208000024889 MECP2 duplication syndrome Diseases 0.000 description 1
- 101150083522 MECP2 gene Proteins 0.000 description 1
- 239000007993 MOPS buffer Substances 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- 101001129124 Mannheimia haemolytica Outer membrane lipoprotein 1 Proteins 0.000 description 1
- 108010049137 Member 1 Subfamily D ATP Binding Cassette Transporter Proteins 0.000 description 1
- 108010090822 Member 8 Subfamily G ATP Binding Cassette Transporter Proteins 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 208000008948 Menkes Kinky Hair Syndrome Diseases 0.000 description 1
- 208000012583 Menkes disease Diseases 0.000 description 1
- 201000011442 Metachromatic leukodystrophy Diseases 0.000 description 1
- 241001074903 Methanobacteria Species 0.000 description 1
- 241000202974 Methanobacterium Species 0.000 description 1
- 241000203353 Methanococcus Species 0.000 description 1
- 241000204675 Methanopyrus Species 0.000 description 1
- 241000205276 Methanosarcina Species 0.000 description 1
- 102100021299 Methyl-CpG-binding domain protein 2 Human genes 0.000 description 1
- 102100039124 Methyl-CpG-binding protein 2 Human genes 0.000 description 1
- 241000589345 Methylococcus Species 0.000 description 1
- 108060004795 Methyltransferase Proteins 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 108020005196 Mitochondrial DNA Proteins 0.000 description 1
- 206010058799 Mitochondrial encephalomyopathy Diseases 0.000 description 1
- 201000002169 Mitochondrial myopathy Diseases 0.000 description 1
- 208000034819 Mobility Limitation Diseases 0.000 description 1
- 206010056886 Mucopolysaccharidosis I Diseases 0.000 description 1
- 208000028781 Mucopolysaccharidosis type 1 Diseases 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 101000981253 Mus musculus GPI-linked NAD(P)(+)-arginine ADP-ribosyltransferase 1 Proteins 0.000 description 1
- 101100078999 Mus musculus Mx1 gene Proteins 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 208000007101 Muscle Cramp Diseases 0.000 description 1
- 241000186359 Mycobacterium Species 0.000 description 1
- 241000187479 Mycobacterium tuberculosis Species 0.000 description 1
- 102100026784 Myelin proteolipid protein Human genes 0.000 description 1
- 102100030856 Myoglobin Human genes 0.000 description 1
- 108010062374 Myoglobin Proteins 0.000 description 1
- 241000863420 Myxococcus Species 0.000 description 1
- 108700037255 NEDD8-activating enzyme E1 catalytic subunit Proteins 0.000 description 1
- 108091061960 Naked DNA Proteins 0.000 description 1
- 108700019961 Neoplasm Genes Proteins 0.000 description 1
- 102000048850 Neoplasm Genes Human genes 0.000 description 1
- 102000048238 Neuregulin-1 Human genes 0.000 description 1
- 108090000556 Neuregulin-1 Proteins 0.000 description 1
- 102100021582 Neurexin-1-beta Human genes 0.000 description 1
- 108010088373 Neurofilament Proteins Proteins 0.000 description 1
- 102000008763 Neurofilament Proteins Human genes 0.000 description 1
- 101100058191 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) bcp-1 gene Proteins 0.000 description 1
- 101100385413 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) csm-3 gene Proteins 0.000 description 1
- 208000010577 Niemann-Pick disease type C Diseases 0.000 description 1
- 108010008858 Nitric Oxide Synthase Type I Proteins 0.000 description 1
- 239000000020 Nitrocellulose Substances 0.000 description 1
- 208000035544 Nonketotic hyperglycinaemia Diseases 0.000 description 1
- 108020004485 Nonsense Codon Proteins 0.000 description 1
- 238000000636 Northern blotting Methods 0.000 description 1
- 102100022676 Nuclear receptor subfamily 4 group A member 2 Human genes 0.000 description 1
- 101000761187 Odontomachus monticola U-poneritoxin(01)-Om1a Proteins 0.000 description 1
- 238000012408 PCR amplification Methods 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 108010011536 PTEN Phosphohydrolase Proteins 0.000 description 1
- 241001386753 Parvibaculum Species 0.000 description 1
- 241000606860 Pasteurella Species 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 102000005877 Peptide Initiation Factors Human genes 0.000 description 1
- 108010044843 Peptide Initiation Factors Proteins 0.000 description 1
- 102000003992 Peroxidases Human genes 0.000 description 1
- 241000009328 Perro Species 0.000 description 1
- 201000004316 Perry syndrome Diseases 0.000 description 1
- 102100032543 Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN Human genes 0.000 description 1
- 102100033623 Phospholipid-transporting ATPase ABCA3 Human genes 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 241000607568 Photobacterium Species 0.000 description 1
- 102100030655 Platelet-activating factor acetylhydrolase IB subunit beta Human genes 0.000 description 1
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 description 1
- 241000605894 Porphyromonas Species 0.000 description 1
- 108010036933 Presenilin-1 Proteins 0.000 description 1
- 108010036908 Presenilin-2 Proteins 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 208000024777 Prion disease Diseases 0.000 description 1
- WDVSHHCDHLJJJR-UHFFFAOYSA-N Proflavine Chemical compound C1=CC(N)=CC2=NC3=CC(N)=CC=C3C=C21 WDVSHHCDHLJJJR-UHFFFAOYSA-N 0.000 description 1
- 208000007932 Progeria Diseases 0.000 description 1
- 208000033063 Progressive myoclonic epilepsy Diseases 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 102000007659 Protein Deglycase DJ-1 Human genes 0.000 description 1
- 108010032428 Protein Deglycase DJ-1 Proteins 0.000 description 1
- 102000001253 Protein Kinase Human genes 0.000 description 1
- 101710188315 Protein X Proteins 0.000 description 1
- 208000033876 Proximal Xq28 duplication syndrome Diseases 0.000 description 1
- 102100037401 Putative uncharacterized protein encoded by MIR7-3HG Human genes 0.000 description 1
- 241000205226 Pyrobaculum Species 0.000 description 1
- 241000205160 Pyrococcus Species 0.000 description 1
- 102000014450 RNA Polymerase III Human genes 0.000 description 1
- 108010078067 RNA Polymerase III Proteins 0.000 description 1
- 101710199540 RNA binding protein fox-1 homolog 1 Proteins 0.000 description 1
- 238000012228 RNA interference-mediated gene silencing Methods 0.000 description 1
- 230000007022 RNA scission Effects 0.000 description 1
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 1
- 101100240886 Rattus norvegicus Nptx2 gene Proteins 0.000 description 1
- 101100047461 Rattus norvegicus Trpm8 gene Proteins 0.000 description 1
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 1
- 101710100969 Receptor tyrosine-protein kinase erbB-3 Proteins 0.000 description 1
- 102100029986 Receptor tyrosine-protein kinase erbB-3 Human genes 0.000 description 1
- 102100029981 Receptor tyrosine-protein kinase erbB-4 Human genes 0.000 description 1
- 101710100963 Receptor tyrosine-protein kinase erbB-4 Proteins 0.000 description 1
- 102100037422 Receptor-type tyrosine-protein phosphatase C Human genes 0.000 description 1
- 102100033617 Retinal-specific phospholipid-transporting ATPase ABCA4 Human genes 0.000 description 1
- 108091028664 Ribonucleotide Proteins 0.000 description 1
- 201000001718 Roberts syndrome Diseases 0.000 description 1
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 1
- SUYXJDLXGFPMCQ-INIZCTEOSA-N SJ000287331 Natural products CC1=c2cnccc2=C(C)C2=Nc3ccccc3[C@H]12 SUYXJDLXGFPMCQ-INIZCTEOSA-N 0.000 description 1
- 101100170553 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) DLD2 gene Proteins 0.000 description 1
- 241000607142 Salmonella Species 0.000 description 1
- 208000021811 Sandhoff disease Diseases 0.000 description 1
- 101100023124 Schizosaccharomyces pombe (strain 972 / ATCC 24843) mfr2 gene Proteins 0.000 description 1
- 102100038376 Serine/threonine-protein kinase PINK1, mitochondrial Human genes 0.000 description 1
- 201000007410 Smith-Lemli-Opitz syndrome Diseases 0.000 description 1
- 208000005392 Spasm Diseases 0.000 description 1
- 208000009415 Spinocerebellar Ataxias Diseases 0.000 description 1
- 241000794282 Staphylococcus pseudintermedius Species 0.000 description 1
- 241000862969 Stella Species 0.000 description 1
- 241000320123 Streptococcus pyogenes M1 GAS Species 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound 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 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 241000205101 Sulfolobus Species 0.000 description 1
- 102100026014 Synembryn-B Human genes 0.000 description 1
- 108091008874 T cell receptors Proteins 0.000 description 1
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 1
- 102000018679 Tacrolimus Binding Proteins Human genes 0.000 description 1
- 108010027179 Tacrolimus Binding Proteins Proteins 0.000 description 1
- 239000004098 Tetracycline Substances 0.000 description 1
- 241000204667 Thermoplasma Species 0.000 description 1
- 241000589596 Thermus Species 0.000 description 1
- 108010022394 Threonine synthase Proteins 0.000 description 1
- 108090000190 Thrombin Proteins 0.000 description 1
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
- 241000283907 Tragelaphus oryx Species 0.000 description 1
- 108090000340 Transaminases Proteins 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 102100040653 Tryptophan 2,3-dioxygenase Human genes 0.000 description 1
- 102100024971 Tryptophan 5-hydroxylase 1 Human genes 0.000 description 1
- 208000007930 Type C Niemann-Pick Disease Diseases 0.000 description 1
- 101150044377 UBA1 gene Proteins 0.000 description 1
- 101150035006 UBA3 gene Proteins 0.000 description 1
- VGQOVCHZGQWAOI-UHFFFAOYSA-N UNPD55612 Natural products N1C(O)C2CC(C=CC(N)=O)=CN2C(=O)C2=CC=C(C)C(O)=C12 VGQOVCHZGQWAOI-UHFFFAOYSA-N 0.000 description 1
- 108010005656 Ubiquitin Thiolesterase Proteins 0.000 description 1
- 102000005918 Ubiquitin Thiolesterase Human genes 0.000 description 1
- 108010046334 Urease Proteins 0.000 description 1
- 208000014769 Usher Syndromes Diseases 0.000 description 1
- 101710177612 Very low-density lipoprotein receptor Proteins 0.000 description 1
- 102100038170 Vesicular inhibitory amino acid transporter Human genes 0.000 description 1
- 108020005202 Viral DNA Proteins 0.000 description 1
- 101150115477 Vldlr gene Proteins 0.000 description 1
- 108091093126 WHP Posttrascriptional Response Element Proteins 0.000 description 1
- 201000006793 Walker-Warburg syndrome Diseases 0.000 description 1
- 208000006254 Wolf-Hirschhorn Syndrome Diseases 0.000 description 1
- 206010048215 Xanthomatosis Diseases 0.000 description 1
- 241000589634 Xanthomonas Species 0.000 description 1
- 101000678336 Xenopus laevis Actin, alpha skeletal muscle 2 Proteins 0.000 description 1
- 101000678338 Xenopus tropicalis Actin, alpha cardiac muscle 2 Proteins 0.000 description 1
- 201000006083 Xeroderma Pigmentosum Diseases 0.000 description 1
- 241000607734 Yersinia <bacteria> Species 0.000 description 1
- 201000004525 Zellweger Syndrome Diseases 0.000 description 1
- 208000036813 Zellweger spectrum disease Diseases 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 108010017070 Zinc Finger Nucleases Proteins 0.000 description 1
- 102100035558 Zinc finger protein GLI2 Human genes 0.000 description 1
- HMNZFMSWFCAGGW-XPWSMXQVSA-N [3-[hydroxy(2-hydroxyethoxy)phosphoryl]oxy-2-[(e)-octadec-9-enoyl]oxypropyl] (e)-octadec-9-enoate Chemical compound CCCCCCCC\C=C\CCCCCCCC(=O)OCC(COP(O)(=O)OCCO)OC(=O)CCCCCCC\C=C\CCCCCCCC HMNZFMSWFCAGGW-XPWSMXQVSA-N 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- DPKHZNPWBDQZCN-UHFFFAOYSA-N acridine orange free base Chemical compound C1=CC(N(C)C)=CC2=NC3=CC(N(C)C)=CC=C3C=C21 DPKHZNPWBDQZCN-UHFFFAOYSA-N 0.000 description 1
- 229940023020 acriflavine Drugs 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000003044 adaptive effect Effects 0.000 description 1
- 201000009628 adenosine deaminase deficiency Diseases 0.000 description 1
- GFFGJBXGBJISGV-UHFFFAOYSA-N adenyl group Chemical group N1=CN=C2N=CNC2=C1N GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 1
- 230000001800 adrenalinergic effect Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 238000001261 affinity purification Methods 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 235000010419 agar Nutrition 0.000 description 1
- 206010064930 age-related macular degeneration Diseases 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 108010029483 alpha 1 Chain Collagen Type I Proteins 0.000 description 1
- 102000009899 alpha Karyopherins Human genes 0.000 description 1
- 108010077099 alpha Karyopherins Proteins 0.000 description 1
- 108010026331 alpha-Fetoproteins Proteins 0.000 description 1
- 108090000185 alpha-Synuclein Proteins 0.000 description 1
- 201000008333 alpha-mannosidosis Diseases 0.000 description 1
- 238000003016 alphascreen Methods 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 229940037003 alum Drugs 0.000 description 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
- ILRRQNADMUWWFW-UHFFFAOYSA-K aluminium phosphate Chemical compound O1[Al]2OP1(=O)O2 ILRRQNADMUWWFW-UHFFFAOYSA-K 0.000 description 1
- 238000000137 annealing Methods 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- VGQOVCHZGQWAOI-HYUHUPJXSA-N anthramycin Chemical compound N1[C@@H](O)[C@@H]2CC(\C=C\C(N)=O)=CN2C(=O)C2=CC=C(C)C(O)=C12 VGQOVCHZGQWAOI-HYUHUPJXSA-N 0.000 description 1
- 210000000628 antibody-producing cell Anatomy 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000001640 apoptogenic effect Effects 0.000 description 1
- 238000003491 array Methods 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-L aspartate group Chemical class N[C@@H](CC(=O)[O-])C(=O)[O-] CKLJMWTZIZZHCS-REOHCLBHSA-L 0.000 description 1
- 239000005441 aurora Substances 0.000 description 1
- 208000029560 autism spectrum disease Diseases 0.000 description 1
- 201000004562 autosomal dominant cerebellar ataxia Diseases 0.000 description 1
- 208000036556 autosomal recessive T cell-negative B cell-negative NK cell-negative due to adenosine deaminase deficiency severe combined immunodeficiency Diseases 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- UCMIRNVEIXFBKS-UHFFFAOYSA-N beta-alanine Chemical group NCCC(O)=O UCMIRNVEIXFBKS-UHFFFAOYSA-N 0.000 description 1
- 229910002056 binary alloy Inorganic materials 0.000 description 1
- 108091008324 binding proteins Proteins 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 238000006664 bond formation reaction Methods 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 210000000845 cartilage Anatomy 0.000 description 1
- 101150038500 cas9 gene Proteins 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 230000001364 causal effect Effects 0.000 description 1
- 230000022131 cell cycle Effects 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 210000003855 cell nucleus Anatomy 0.000 description 1
- 230000030570 cellular localization Effects 0.000 description 1
- 208000025434 cerebellar degeneration Diseases 0.000 description 1
- 208000016886 cerebral arteriopathy with subcortical infarcts and leukoencephalopathy Diseases 0.000 description 1
- 230000006239 cerebral cortex development Effects 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 208000003131 cerebrooculofacioskeletal syndrome 1 Diseases 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 229960004926 chlorobutanol Drugs 0.000 description 1
- 229960003677 chloroquine Drugs 0.000 description 1
- WHTVZRBIWZFKQO-UHFFFAOYSA-N chloroquine Natural products ClC1=CC=C2C(NC(C)CCCN(CC)CC)=CC=NC2=C1 WHTVZRBIWZFKQO-UHFFFAOYSA-N 0.000 description 1
- 229910052804 chromium Inorganic materials 0.000 description 1
- 239000011651 chromium Substances 0.000 description 1
- ZYVSOIYQKUDENJ-WKSBCEQHSA-N chromomycin A3 Chemical compound O([C@@H]1C[C@@H](O[C@H](C)[C@@H]1OC(C)=O)OC=1C=C2C=C3C[C@H]([C@@H](C(=O)C3=C(O)C2=C(O)C=1C)O[C@@H]1O[C@H](C)[C@@H](O)[C@H](O[C@@H]2O[C@H](C)[C@@H](O)[C@H](O[C@@H]3O[C@@H](C)[C@H](OC(C)=O)[C@@](C)(O)C3)C2)C1)[C@H](OC)C(=O)[C@@H](O)[C@@H](C)O)[C@@H]1C[C@@H](O)[C@@H](OC)[C@@H](C)O1 ZYVSOIYQKUDENJ-WKSBCEQHSA-N 0.000 description 1
- 235000020971 citrus fruits Nutrition 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 208000003536 colpocephaly Diseases 0.000 description 1
- 238000012875 competitive assay Methods 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 238000004624 confocal microscopy Methods 0.000 description 1
- 201000006815 congenital muscular dystrophy Diseases 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 101150055601 cops2 gene Proteins 0.000 description 1
- 239000011258 core-shell material Substances 0.000 description 1
- 210000000877 corpus callosum Anatomy 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 230000000139 costimulatory effect Effects 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000007123 defense Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 239000000412 dendrimer Substances 0.000 description 1
- 229920000736 dendritic polymer Polymers 0.000 description 1
- 239000005547 deoxyribonucleotide Substances 0.000 description 1
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- QONQRTHLHBTMGP-UHFFFAOYSA-N digitoxigenin Natural products CC12CCC(C3(CCC(O)CC3CC3)C)C3C11OC1CC2C1=CC(=O)OC1 QONQRTHLHBTMGP-UHFFFAOYSA-N 0.000 description 1
- SHIBSTMRCDJXLN-KCZCNTNESA-N digoxigenin Chemical compound C1([C@@H]2[C@@]3([C@@](CC2)(O)[C@H]2[C@@H]([C@@]4(C)CC[C@H](O)C[C@H]4CC2)C[C@H]3O)C)=CC(=O)OC1 SHIBSTMRCDJXLN-KCZCNTNESA-N 0.000 description 1
- 102000004419 dihydrofolate reductase Human genes 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 230000009429 distress Effects 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 241001493065 dsRNA viruses Species 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 208000025688 early-onset autosomal dominant Alzheimer disease Diseases 0.000 description 1
- 230000005670 electromagnetic radiation Effects 0.000 description 1
- 210000002257 embryonic structure Anatomy 0.000 description 1
- 108010025678 empty spiracles homeobox proteins Proteins 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 230000012202 endocytosis Effects 0.000 description 1
- 210000003989 endothelium vascular Anatomy 0.000 description 1
- 238000001952 enzyme assay Methods 0.000 description 1
- 208000028329 epileptic seizure Diseases 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- ZMMJGEGLRURXTF-UHFFFAOYSA-N ethidium bromide Chemical compound [Br-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CC)=C1C1=CC=CC=C1 ZMMJGEGLRURXTF-UHFFFAOYSA-N 0.000 description 1
- 229960005542 ethidium bromide Drugs 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 229940073505 ethyl vanillin Drugs 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000002964 excitative effect Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 208000015756 familial Alzheimer disease Diseases 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 108010021843 fluorescent protein 583 Proteins 0.000 description 1
- 108091006047 fluorescent proteins Proteins 0.000 description 1
- 102000034287 fluorescent proteins Human genes 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 201000008049 fucosidosis Diseases 0.000 description 1
- 210000001222 gaba-ergic neuron Anatomy 0.000 description 1
- 229960003692 gamma aminobutyric acid Drugs 0.000 description 1
- 238000003500 gene array Methods 0.000 description 1
- 238000001476 gene delivery Methods 0.000 description 1
- 230000009368 gene silencing by RNA Effects 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000003862 glucocorticoid Substances 0.000 description 1
- 201000011205 glycine encephalopathy Diseases 0.000 description 1
- 229940096919 glycogen Drugs 0.000 description 1
- 201000004502 glycogen storage disease II Diseases 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 1
- 208000014752 hemophagocytic syndrome Diseases 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 239000000833 heterodimer Substances 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 102000047882 human INSR Human genes 0.000 description 1
- 102000056115 human SYN1 Human genes 0.000 description 1
- 210000005119 human aortic smooth muscle cell Anatomy 0.000 description 1
- 239000003906 humectant Substances 0.000 description 1
- BHEPBYXIRTUNPN-UHFFFAOYSA-N hydridophosphorus(.) (triplet) Chemical group [PH] BHEPBYXIRTUNPN-UHFFFAOYSA-N 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000008076 immune mechanism Effects 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 230000003053 immunization Effects 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 238000003119 immunoblot Methods 0.000 description 1
- 230000000984 immunochemical effect Effects 0.000 description 1
- 230000007813 immunodeficiency Effects 0.000 description 1
- 238000010166 immunofluorescence Methods 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 238000000530 impalefection Methods 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000007901 in situ hybridization Methods 0.000 description 1
- 238000003017 in situ immunoassay Methods 0.000 description 1
- 208000023692 inborn mitochondrial myopathy Diseases 0.000 description 1
- 206010022000 influenza Diseases 0.000 description 1
- 108700032552 influenza virus INS1 Proteins 0.000 description 1
- 230000004941 influx Effects 0.000 description 1
- 208000019143 inherited prion disease Diseases 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 238000002743 insertional mutagenesis Methods 0.000 description 1
- 239000012212 insulator Substances 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 208000017476 juvenile neuronal ceroid lipofuscinosis Diseases 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 238000011005 laboratory method Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- IXHBTMCLRNMKHZ-LBPRGKRZSA-N levobunolol Chemical compound O=C1CCCC2=C1C=CC=C2OC[C@@H](O)CNC(C)(C)C IXHBTMCLRNMKHZ-LBPRGKRZSA-N 0.000 description 1
- 210000005228 liver tissue Anatomy 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 230000002101 lytic effect Effects 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 210000005075 mammary gland Anatomy 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- CFCUWKMKBJTWLW-BKHRDMLASA-N mithramycin Chemical compound O([C@@H]1C[C@@H](O[C@H](C)[C@H]1O)OC=1C=C2C=C3C[C@H]([C@@H](C(=O)C3=C(O)C2=C(O)C=1C)O[C@@H]1O[C@H](C)[C@@H](O)[C@H](O[C@@H]2O[C@H](C)[C@H](O)[C@H](O[C@@H]3O[C@H](C)[C@@H](O)[C@@](C)(O)C3)C2)C1)[C@H](OC)C(=O)[C@@H](O)[C@@H](C)O)[C@H]1C[C@@H](O)[C@H](O)[C@@H](C)O1 CFCUWKMKBJTWLW-BKHRDMLASA-N 0.000 description 1
- 201000011540 mitochondrial DNA depletion syndrome 4a Diseases 0.000 description 1
- 201000002273 mucopolysaccharidosis II Diseases 0.000 description 1
- 208000022018 mucopolysaccharidosis type 2 Diseases 0.000 description 1
- 208000011045 mucopolysaccharidosis type 3 Diseases 0.000 description 1
- 208000025855 muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4 Diseases 0.000 description 1
- UPBAOYRENQEPJO-UHFFFAOYSA-N n-[5-[[5-[(3-amino-3-iminopropyl)carbamoyl]-1-methylpyrrol-3-yl]carbamoyl]-1-methylpyrrol-3-yl]-4-formamido-1-methylpyrrole-2-carboxamide Chemical compound CN1C=C(NC=O)C=C1C(=O)NC1=CN(C)C(C(=O)NC2=CN(C)C(C(=O)NCCC(N)=N)=C2)=C1 UPBAOYRENQEPJO-UHFFFAOYSA-N 0.000 description 1
- 239000002070 nanowire Substances 0.000 description 1
- 201000007601 neurodegeneration with brain iron accumulation Diseases 0.000 description 1
- 230000000626 neurodegenerative effect Effects 0.000 description 1
- 230000007472 neurodevelopment Effects 0.000 description 1
- 210000005044 neurofilament Anatomy 0.000 description 1
- 201000008051 neuronal ceroid lipofuscinosis Diseases 0.000 description 1
- 201000007607 neuronal ceroid lipofuscinosis 3 Diseases 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229920001220 nitrocellulos Polymers 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 230000037434 nonsense mutation Effects 0.000 description 1
- 230000009438 off-target cleavage Effects 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 208000001749 optic atrophy Diseases 0.000 description 1
- 208000027014 optic atrophy 1 Diseases 0.000 description 1
- 201000008152 organic acidemia Diseases 0.000 description 1
- 230000011164 ossification Effects 0.000 description 1
- 210000000963 osteoblast Anatomy 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 239000006179 pH buffering agent Substances 0.000 description 1
- 229940090668 parachlorophenol Drugs 0.000 description 1
- 102000045222 parkin Human genes 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 238000010647 peptide synthesis reaction Methods 0.000 description 1
- 239000000816 peptidomimetic Substances 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- 210000002824 peroxisome Anatomy 0.000 description 1
- 229940067107 phenylethyl alcohol Drugs 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- 108091005981 phosphorylated proteins Proteins 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 230000037081 physical activity Effects 0.000 description 1
- 210000002706 plastid Anatomy 0.000 description 1
- 229960003171 plicamycin Drugs 0.000 description 1
- 210000001778 pluripotent stem cell Anatomy 0.000 description 1
- 229960000502 poloxamer Drugs 0.000 description 1
- 229920001983 poloxamer Polymers 0.000 description 1
- 230000008488 polyadenylation Effects 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 125000004424 polypyridyl Polymers 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 230000029279 positive regulation of transcription, DNA-dependent Effects 0.000 description 1
- 235000010241 potassium sorbate Nutrition 0.000 description 1
- 239000004302 potassium sorbate Substances 0.000 description 1
- 229940069338 potassium sorbate Drugs 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 229960000286 proflavine Drugs 0.000 description 1
- 201000001204 progressive myoclonus epilepsy Diseases 0.000 description 1
- XJMOSONTPMZWPB-UHFFFAOYSA-M propidium iodide Chemical compound [I-].[I-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CCC[N+](C)(CC)CC)=C1C1=CC=CC=C1 XJMOSONTPMZWPB-UHFFFAOYSA-M 0.000 description 1
- 239000000473 propyl gallate Substances 0.000 description 1
- 229940075579 propyl gallate Drugs 0.000 description 1
- 235000010388 propyl gallate Nutrition 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 108010043671 prostatic acid phosphatase Proteins 0.000 description 1
- 108060006633 protein kinase Proteins 0.000 description 1
- 238000001273 protein sequence alignment Methods 0.000 description 1
- 230000012743 protein tagging Effects 0.000 description 1
- 230000006337 proteolytic cleavage Effects 0.000 description 1
- ZJFJVRPLNAMIKH-UHFFFAOYSA-N pseudo-u Chemical compound O=C1NC(=O)C(C)=CN1C1OC(COP(O)(=S)OC2C(OC(C2)N2C(N=C(N)C=C2)=O)COP(O)(=S)OC2C(OC(C2)N2C(N=C(N)C=C2)=O)COP(O)(=S)OC2C(OC(C2)N2C(N=C(N)C=C2)=O)COP(O)(=S)OC2C(OC(C2)N2C(NC(=O)C(C)=C2)=O)COP(O)(=S)OC2C(OC(C2)N2C3=C(C(NC(N)=N3)=O)N=C2)COP(O)(=S)OC2C(OC(C2)N2C3=NC=NC(N)=C3N=C2)COP(O)(=S)OC2C(OC(C2)N2C3=NC=NC(N)=C3N=C2)COP(O)(=S)OC2C(OC(C2)N2C(N=C(N)C=C2)=O)COP(O)(=S)OC2C(OC(C2)N2C(NC(=O)C(C)=C2)=O)COP(O)(=S)OC2C(OC(C2)N2C(NC(=O)C(C)=C2)=O)COP(O)(=S)OC2C(OC(C2)N2C3=C(C(NC(N)=N3)=O)N=C2)COP(O)(=S)OC2C(OC(C2)N2C3=C(C(NC(N)=N3)=O)N=C2)COP(O)(=S)OC2C(OC(C2)N2C3=C(C(NC(N)=N3)=O)N=C2)COP(O)(=S)OC2C(OC(C2)N2C3=NC=NC(N)=C3N=C2)CO)C(O)C1 ZJFJVRPLNAMIKH-UHFFFAOYSA-N 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 238000012207 quantitative assay Methods 0.000 description 1
- 239000013645 rAAV1 vector Substances 0.000 description 1
- 239000013646 rAAV2 vector Substances 0.000 description 1
- 108700022487 rRNA Genes Proteins 0.000 description 1
- 238000003127 radioimmunoassay Methods 0.000 description 1
- 102000005912 ran GTP Binding Protein Human genes 0.000 description 1
- 238000003753 real-time PCR Methods 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 230000009711 regulatory function Effects 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000016914 response to endoplasmic reticulum stress Effects 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- 238000010839 reverse transcription Methods 0.000 description 1
- 239000002336 ribonucleotide Substances 0.000 description 1
- 125000002652 ribonucleotide group Chemical group 0.000 description 1
- 108020004418 ribosomal RNA Proteins 0.000 description 1
- 108091092562 ribozyme Proteins 0.000 description 1
- 229910052707 ruthenium Inorganic materials 0.000 description 1
- 238000007480 sanger sequencing Methods 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 230000005783 single-strand break Effects 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 238000011895 specific detection Methods 0.000 description 1
- 208000002320 spinal muscular atrophy Diseases 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 108010042747 stallimycin Proteins 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 229940044609 sulfur dioxide Drugs 0.000 description 1
- 235000010269 sulphur dioxide Nutrition 0.000 description 1
- 239000002344 surface layer Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000005062 synaptic transmission Effects 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 238000010809 targeting technique Methods 0.000 description 1
- 210000002435 tendon Anatomy 0.000 description 1
- 229960002180 tetracycline Drugs 0.000 description 1
- 229930101283 tetracycline Natural products 0.000 description 1
- 235000019364 tetracycline Nutrition 0.000 description 1
- 150000003522 tetracyclines Chemical class 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 229940094937 thioredoxin Drugs 0.000 description 1
- 229960004072 thrombin Drugs 0.000 description 1
- 230000036962 time dependent Effects 0.000 description 1
- 102000014898 transaminase activity proteins Human genes 0.000 description 1
- 230000005026 transcription initiation Effects 0.000 description 1
- 230000037426 transcriptional repression Effects 0.000 description 1
- 230000031998 transcytosis Effects 0.000 description 1
- 238000011426 transformation method Methods 0.000 description 1
- 230000010474 transient expression Effects 0.000 description 1
- 238000003146 transient transfection Methods 0.000 description 1
- 230000014621 translational initiation Effects 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 230000005760 tumorsuppression Effects 0.000 description 1
- 238000010396 two-hybrid screening Methods 0.000 description 1
- 108091005990 tyrosine-phosphorylated proteins Proteins 0.000 description 1
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 238000005199 ultracentrifugation Methods 0.000 description 1
- 208000030954 urea cycle disease Diseases 0.000 description 1
- 210000003501 vero cell Anatomy 0.000 description 1
- 239000007762 w/o emulsion Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 210000005253 yeast cell Anatomy 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- 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 RNAses, DNAses
-
- 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
- C12N15/10—Processes for the isolation, preparation or purification of DNA or RNA
- C12N15/1034—Isolating an individual clone by screening libraries
- C12N15/1082—Preparation or screening gene libraries by chromosomal integration of polynucleotide sequences, HR-, site-specific-recombination, transposons, viral vectors
-
- 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
-
- 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
- C12N15/82—Vectors or expression systems specially adapted for eukaryotic hosts for plant cells, e.g. plant artificial chromosomes (PACs)
- C12N15/8201—Methods for introducing genetic material into plant cells, e.g. DNA, RNA, stable or transient incorporation, tissue culture methods adapted for transformation
- C12N15/8213—Targeted insertion of genes into the plant genome by homologous recombination
-
- 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
-
- 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
-
- 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
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/96—Stabilising an enzyme by forming an adduct or a composition; Forming enzyme conjugates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- 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
-
- 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
- C12N2800/22—Vectors comprising a coding region that has been codon optimised for expression in a respective host
-
- 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
- C12N2810/00—Vectors comprising a targeting moiety
- C12N2810/10—Vectors comprising a non-peptidic targeting moiety
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Genetics & Genomics (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Biotechnology (AREA)
- Biomedical Technology (AREA)
- General Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Microbiology (AREA)
- Biophysics (AREA)
- Plant Pathology (AREA)
- Physics & Mathematics (AREA)
- Medicinal Chemistry (AREA)
- Virology (AREA)
- Cell Biology (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Crystallography & Structural Chemistry (AREA)
- Bioinformatics & Computational Biology (AREA)
- Mycology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Ophthalmology & Optometry (AREA)
- Epidemiology (AREA)
- Enzymes And Modification Thereof (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Breeding Of Plants And Reproduction By Means Of Culturing (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Immobilizing And Processing Of Enzymes And Microorganisms (AREA)
Abstract
【解決手段】本発明は、配列の操作および/または標的配列の活性のための系、方法、および組成物のエンジニアリングおよび最適化を提供する。特にCasオルソログ酵素を含むCRISPR複合体の成分に関する組成物および方法が提供される。
【選択図】図1
Description
本出願は、2013年6月17日に出願された米国仮特許出願第61/836,101号明細書、標題ENGINEERING AND OPTIMIZATION OF IMPROVED SYSTEMS,METHODS AND ENZYME COMPOSITIONS FOR SEQUENCE MANIPULATIONの優先権を主張する。本出願は、米国仮特許出願第61/758,468号明細書;同第61/769,046号明細書;同第61/802,174号明細書;同第61/806,375号明細書;同第61/814,263号明細書;同第61/819,803号明細書および同第61/828,130号明細書の優先権も主張し、それぞれ標題ENGINEERING AND OPTIMIZATION OF SYSTEMS,METHODS AND COMPOSITIONS FOR SEQUENCE MANIPULATIONであり、それぞれ2013年1月30日;2013年2月25日、2013年3月15日;2013年3月28日、2013年4月20日;2013年5月6日および2013年5月28日に出願されたものである。本出願は、米国仮特許出願第61/736,527号明細書および同第61/748,427号明細書の優先権も主張し、両方とも標題SYSTEMS METHODS AND COMPOSITIONS FOR SEQUENCE MANIPULATIONであり、それぞれ2012年12月12日および2013年1月2日に出願されたものである。それぞれ2013年3月15日および2013年6月17日に出願された米国仮特許出願第61/791,409号明細書および同第61/835,931号明細書の優先権も主張される。
それぞれ2013年6月17日に出願された米国仮特許出願第61/836,127号明細書、同第61/835,936号明細書、同第61/836,080号明細書、同第61/836,123号明細書、および同第61/835,973号明細書が参照される。
本発明は、米国国立衛生研究所(National Institutes of Health)により助成されたNIHパイオニアアワード(1DP1MH100706)のもと政府支援によりなされた。米国政府は本発明において一定の権利を有する。
A)−I.CRISPR−Cas系キメラRNA(chiRNA)ポリヌクレオチド配列であって、
(a)真核細胞中の標的配列にハイブリダイズし得るガイド配列
(b)tracrメイト配列、および
(c)tracr配列
を含むポリヌクレオチド配列、および
II.少なくとも1つ以上の核局在化配列を含むCRISPR酵素をコードするポリヌクレオチド配列
を含み、
(a)、(b)および(c)は、5’から3’配向で配置されており、
転写されるとtracrメイト配列がtracr配列にハイブリダイズし、かつガイド配列が標的配列へのCRISPR複合体の配列特異的結合を指向し、
CRISPR複合体は、(1)標的配列にハイブリダイズされるガイド配列、および(2)tracr配列にハイブリダイズされるtracrメイト配列と複合体形成しているCRISPR酵素を含み、CRISPR酵素をコードするポリヌクレオチド配列は、DNAまたはRNAである
天然に存在しないまたはエンジニアリングされた組成物
または
(B)I.ポリヌクレオチドであって、
(a)原核細胞中の標的配列にハイブリダイズし得るガイド配列、および
(b)少なくとも1つ以上のtracrメイト配列
を含むポリヌクレオチド、
II.CRISPR酵素をコードするポリヌクレオチド配列、および
III.tracr配列を含むポリヌクレオチド配列
を含み、
転写されるとtracrメイト配列がtracr配列にハイブリダイズし、かつガイド配列が標的配列へのCRISPR複合体の配列特異標的結合を指向し、
CRISPR複合体は、(1)標的配列にハイブリダイズされるガイド配列、および(2)tracr配列にハイブリダイズされるtracrメイト配列と複合体形成しているCRISPR酵素を含み、CRISPR酵素をコードするポリヌクレオチド配列は、DNAまたはRNAであり、
CRISPR酵素は、コリネバクター属(Corynebacter)、ステレラ属(Sutterella)、レジオネラ属(Legionella)、トレポネーマ属(Treponema)、フィリファクター属(Filifactor)、ユーバクテリウム属(Eubacterium)、ストレプトコッカス属(Streptococcus)、ラクトバシラス属(Lactobacillus)、マイコプラズマ属(Mycoplasma)、バクテロイデス属(Bacteroides)、フラビイボラ属(Flaviivola)、フラボバクテリウム属(Flavobacterium)、スフェロケタ属(Sphaerochaeta)、アゾスピリラム属(Azospirillum)、グルコンアセトバクター属(Gluconacetobacter)、ネイセリア属(Neisseria)、ロゼブリア属(Roseburia)、パービバキュラム属(Parvibaculum)、スタフィロコッカス属(Staphylococcus)、ニトラティフラクター属(Nitratifractor)、マイコプラズマ属(Mycoplasma)およびカンピロバクター属(Campylobacter)からなる群に属する属のCas9オルソログである
天然に存在しないまたはエンジニアリングされた組成物に関する組成物および方法を提供する。
−規定のサイズを有するCRISPR酵素が選択され、少なくとも500アミノ酸、少なくとも800〜899アミノ酸、少なくとも900〜999アミノ酸、少なくとも1000〜1099アミノ酸、少なくとも1100〜1199アミノ酸、少なくとも1200〜1299アミノ酸、少なくとも1300〜1399アミノ酸、少なくとも1400〜1499アミノ酸、少なくとも1500〜1599アミノ酸、少なくとも1600〜1699アミノ酸または少なくとも2000アミノ酸の長さを有し;
−および/またはCRISPR酵素は、対応する野生型CRISPR酵素と比較してトランケートされており;
−および/またはCRISPR酵素は、標的配列の局在における両方の鎖の開裂を指向するヌクレアーゼであり、もしくはCRISPR酵素は、標的配列の局在における一方の鎖の開裂を指向するニッカーゼであり;
−および/またはガイド配列は、少なくとも10、少なくとも15または少なくとも20ヌクレオチドを含み;
−および/またはCRISPR酵素は、コドン最適化されており、もしくは真核細胞中の発現のためにコドン最適化されており;
−および/またはCRISPR酵素は、1つ以上の突然変異を含み;
−および/またはCRISPR酵素は、キメラCRISPR酵素を含み;
−および/またはCRISPR酵素は、本明細書において考察される1つ以上の他の特質を有する。
I.第1のCRISPR−Cas系キメラRNA(chiRNA)ポリヌクレオチド配列に作動可能に結合している第1の調節エレメント(第1のポリヌクレオチド配列は、
(i)生物の細胞中の第1のゲノム遺伝子座における第1の標的配列にハイブリダイズし得る第1のガイド配列
(ii)第1のtracrメイト配列、および
(iii)第1のtracr配列
を含む)、および
II.第2のCRISPR−Cas系キメラRNA(chiRNA)ポリヌクレオチド配列に作動可能に結合している第2の調節エレメント(第2のポリヌクレオチド配列は、
(i)生物の細胞中の第2のゲノム遺伝子座における第2の標的配列にハイブリダイズし得る第2のガイド配列、
(ii)第2のtracrメイト配列、および
(iii)第2のtracr配列
を含む)、および
III.少なくとも1つ以上の核局在化配列を含み、第1の機能ドメインに作動可能に結合している第1のCRISPR酵素をコードする酵素コード配列に作動可能に結合している第3の調節エレメント、
IV.少なくとも1つ以上の核局在化配列を含み、第2の機能ドメインに作動可能に結合している第2のCRISPR酵素をコードする酵素コード配列に作動可能に結合している第4の調節エレメント
を含み、IおよびIIの(i)、(ii)および(iii)は、5’から3’配向で配置されており、成分I、II、IIIおよびIVは、系の同一または異なるベクター上にあり、転写されるとそれぞれのtracrメイト配列gあgcr配列にハイブリダイズし、かつ第1および第2のガイド配列が第1および第2の標的配列への第1および第2のCRISPR複合体の配列特異的結合を指向し、CRISPR複合体は、(1)標的配列にハイブリダイズされるガイド配列、および(2)tracr配列にハイブリダイズされるtracrメイト配列と複合体形成しているCRISPR酵素を含み、CRISPR酵素の発現は、標的配列の操作を提供し、第1および第2のCRISPR酵素は、2つ以上の突然変異をそれぞれ含み、第1および第2のCRISPR酵素は、コリネバクター属(Corynebacter)、ステレラ属(Sutterella)、レジオネラ属(Legionella)、トレポネーマ属(Treponema)、フィリファクター属(Filifactor)、ユーバクテリウム属(Eubacterium)、ストレプトコッカス属(Streptococcus)、ラクトバシラス属(Lactobacillus)、マイコプラズマ属(Mycoplasma)、バクテロイデス属(Bacteroides)、フラビイボラ属(Flaviivola)、フラボバクテリウム属(Flavobacterium)、スフェロケタ属(Sphaerochaeta)、アゾスピリラム属(Azospirillum)、グルコンアセトバクター属(Gluconacetobacter)、ネイセリア属(Neisseria)、ロゼブリア属(Roseburia)、パービバキュラム属(Parvibaculum)、スタフィロコッカス属(Staphylococcus)、ニトラティフラクター属(Nitratifractor)、マイコプラズマ属(Mycoplasma)およびカンピロバクター属(Campylobacter)からなる群に属する属のCas9オルソログである1つ以上のベクターを含むベクター系を含む天然に存在しないまたはエンジニアリングされた組成物を送達することを含み、第1のゲノム遺伝子座を、第1の機能ドメインの活性によりモジュレートし、第2のゲノム遺伝子座を、第2の機能ドメインの活性によりモジュレートする方法を提供する。さらなる実施形態において、第1の機能ドメインは、転写アクチベーター、転写リプレッサー、リコンビナーゼ、トランスポーゼース、ヒストンリモデラー、DNAメチルトランスフェラーゼ、クリプトクロムおよび光誘導性/制御性ドメインまたは化学誘導性/制御性ドメインからなる群から選択される。さらなる実施形態において、第2の機能ドメインは、転写アクチベーター、転写リプレッサー、リコンビナーゼ、トランスポーゼース、ヒストンリモデラー、DNAメチルトランスフェラーゼ、クリプトクロムおよび光誘導性/制御性ドメインまたは化学誘導性/制御性ドメインからなる群から選択される。好ましい実施形態において、第1または第2のCRISPR酵素は、ステレラ・ウォズワーセンシス(Sutterella wadsworthensis)Cas9、フィリファクター・アロシス(Filifactor alocis)Cas9、ラクトバシラス・ジョンソニイ(Lactobacillus johnsonii)Cas9、カンピロバクター・ラリ(Campylobacter lari)Cas9、コリネバクター・ジフテリエ(Corynebacter diptheriae)Cas9、パービバキュラム・ラバメンティボランス(Parvibaculum lavamentivorans)Cas9、マイコプラズマ・ガリセプティカム(Mycoplasma gallisepticum)Cas9、黄色ブドウ球菌(Staphylococcus aureus subsubspecies Aureus)Cas9、レジオネラ・ニューモフィラ(Legionella pneumophila)Paris Cas9、トレポネーマ・デンティコラ(Treponema denticola)Cas9、スタフィロコッカス・シュードインターメディアス(Staphylococcus pseudintermedius)Cas9、ネイセリア・シネレア(Neisseria cinerea)Cas9である。
NHEJ媒介遺伝子ノックアウトを達成するため:
単一ウイルスベクター:
2つ以上の発現カセットを含有するベクター:
プロモーター−Cas9コード核酸分子−ターミネーター
プロモーター−gRNA1−ターミネーター
プロモーター−gRNA2−ターミネーター
プロモーター−gRNA(N)−ターミネーター(ベクターのサイズ限界まで)
二重ウイルスベクター:
Cas9の発現をドライブするための1つの発現カセットを含有するベクター1
プロモーター−Cas9コード核酸分子−ターミネーター
1つ以上のガイドRNAの発現をドライブするためのもう1つの発現カセットを含有するベクター2
プロモーター−gRNA1−ターミネーター
プロモーター−gRNA(N)−ターミネーター(ベクターのサイズ限界まで)
AAV ITRは、プロモーターとして機能し得:これは、追加のプロモーターエレメント(ベクター中のスペースを占め得る)の必要性の排除に有利である。追加スペースの制限解放を使用して追加のエレメント(gRNAなど)の発現をドライブすることができる。また、ITR活性は相対的に弱く、したがってそれを使用してCas9の過剰発現に起因する毒性を低減させることができる。
肝臓発現のため、アルブミンプロモーターを使用することができる。
肺発現のため、SP−Bを使用することができる。
内皮細胞のため、ICAMを使用することができる。
造血細胞のため、IFNベータまたはCD45を使用することができる。
骨芽細胞のため、OG−2を使用することができる。
ガイドRNAをドライブするために使用されるプロモーターは、以下を含み得る:
PolIIIプロモーター、例えば、U6またはH1
gRNAを発現させるためのPolIIプロモーターおよびイントロン性カセットの使用
本出願人らは、小分子量を有するCas9についてメタゲノム検索を実施した。ほとんどのCas9オルソログはかなり大きい。多くの公知のCas9オルソログは、巨大であり、1300を超えるアミノ酸を含有する。例えばSpCas9は約1368アミノ酸長であり、これは大き過ぎるため送達用のウイルスベクターへのパッケージングが容易でない。Cas9ホモログの長さ分布を表すグラフが図6に示される。グラフは、GenBankに寄託されている配列から作成される。配列の中には誤って注釈されているものもあり、従って各長さについての正確な度数は必ずしも正しいとは限らない。それでもなお、これによりCas9タンパク質の分布の概観が得られ、より短いCas9ホモログの存在が示唆される。
野生型CRISPR−Cas系は、細菌および古細菌にわたる多様な種により用いられる侵入外因性DNAに対する適応免疫機序である。II型CRISPR−Cas系は、CRISPR遺伝子座中への外来DNAの「獲得」を担うタンパク質をコードする遺伝子のセット、およびDNA開裂機序の「実行」をコードする遺伝子のセットからなり;これらは、DNAヌクレアーゼ(Cas9)、非コードトランス活性化crRNA(tracrRNA)、およびダイレクトリピートによりフランキングされている外来DNA由来スペーサーのアレイ(crRNA)を含む。Cas9による成熟時、tracRNAおよびcrRNA二本鎖は、Cas9ヌクレアーゼをスペーサーガイド配列により規定される標的DNA配列にガイドし、開裂に要求され、それぞれのCRISPR−Cas系に特異的な標的DNA中の短鎖配列モチーフ付近のDNAの二本鎖切断を媒介する。II型CRISPR−Cas系は、細菌界全体にわたり見出されており、Cas9タンパク質配列およびサイズ、tracrRNAおよびcrRNAダイレクトリピート配列、それらのエレメントのゲノム構成、ならびに標的開裂のためのモチーフ要件は高度に多様である。ある種は、複数の区別されるCRISPR−Cas系を有し得る。
本出願人らは、真核細胞中の発現を向上させるためのコドン最適化Cas9オルソログを生成した。
本実施例において、本出願人らは、以下の突然変異がSpCas9をニック形成酵素に変換し得ることを示す:D10A、E762A、H840A、N854A、N863A、D986A。
機能向上または新たな機能の開発のため、本出願人らは、異なるCas9オルソログからの断片を組み合わせることによりキメラCas9タンパク質を生成した。
>St1(N)Sp(C)Cas9
a.毒性の低減
b.真核細胞中の発現の改善
c.特異性の向上
d.タンパク質の分子量の低減、異なるCas9ホモログからの最小ドメインを組み合わせることによるより小さいタンパク質の作製。
e.PAM配列要件の変更
インビボ送達−AAV法
AAVは、数個の理由について他のウイルスベクターと比べて有利である:
・毒性が低い(これは、免疫応答を活性化し得る細胞粒子の超遠心を要求しない精製法に起因し得る)
・それが宿主ゲノム中にインテグレートしないため、挿入突然変異導入を引き起こす確率が低い。
Cas9を送達する方法
Chlamydomonas Resource Centerからのコナミドリムシ(Chlamydomonas reinhardtii)株CC−124およびCC−125を、エレクトロポレーションに使用する。エレクトロポレーションプロトコルは、GeneArt Chlamydomonas Engineeringキット(tools.invitrogen.com/content/sfs/manuals/geneart_chlamy_kits_man.pdfにおけるウェブサイト情報)からの標準的な推奨プロトコルに従う。
哺乳動物細胞中の機能ゲノムエンジニアリングツールとしての化膿性連鎖球菌(Streptococcus pyogenes)(Sp)およびストレプトコッカス・サーモフィラス(Streptococcus thermophiles)(St)CRISPR/Cas系の同定後に本出願人らがII型CRISPR/Cas系を多様性のさらなる利用を求めるため、このプロジェクトを開始した。
(1)より高い効率および/または特異性を有するCRISPR/Cas系
(2)より広い範囲のゲノム遺伝子座のターゲティングを可能とする異なるプロトスペーサー隣接モチーフ(PAM)を有するCRISPR/Cas系
(3)より小さいサイズを有するCRISPR/Cas系(したがって、本出願人らは、それらをインビボで単一ベクター中で、パッケージングサイズ限界(現行のSpまたはSt系は、4.7kbのこの限界を超過する)を有する哺乳動物ウイルス送達系、例えば、アデノ随伴ウイルス(AAV)ベクターにより送達することができる)
および他の所望の形質。
1.Cong,L.et al.Multiplex genome engineering using CRISPR/Cas systems.Science 339,819−823(2013)
2.Mali,P.et al.RNA−Guided Human Genome Engineering via Cas9.Science 339,823−826(2013).
3.Jinek,M.et al.RNA−programmed genome editing in human cells.eLife 2,e00471 (2013).
4.Cho,S.W.,Kim,S.,Kim,J.M.&Kim,J.S.Targeted genome engineering in human cells with the Cas9 RNA−guided endonuclease.Nat Biotechnol 31,230−232(2013).
5.Deltcheva,E.et al.CRISPR RNA maturation by trans−encoded small RNA and host factor RNase III.Nature 471,602−607(2011).
6.Jinek,M.et al.A programmable dual−RNA−guided DNA endonuclease in adaptive bacterial immunity.Science 337,816−821(2012).
7.Wang,H.et al.One−Step Generation of Mice Carrying Mutations in Multiple Genes by CRISPR/Cas−Mediated Genome Engineering.Cell 153,910−918(2013).
8.Guschin,D.Y.et al.A rapid and general assay for monitoring endogenous gene modification.Methods Mol Biol 649,247−256(2010).
9.Bogenhagen,D.F.&Brown,D.D.Nucleotide sequences in Xenopus 5S DNA required for transcription termination.Cell 24,261−270(1981).
10.Hwang,W.Y.et al.Efficient genome editing in zebrafish using a CRISPR−Cas system. Nat Biotechnol 31,227−229(2013).
11.Bultmann,S.et al.Targeted transcriptional activation of silent oct4 pluripotency gene by combining designer TALEs and inhibition of epigenetic modifiers.Nucleic Acids Res 40,5368−5377(2012).
12.Valton,J.et al.Overcoming transcription activator−like effector (TALE) DNA binding domain sensitivity to cytosine methylation.J Biol Chem 287,38427−38432 (2012).
13.Christian,M.et al.Targeting DNA double−strand breaks with TAL effector nucleases.Genetics 186,757−761(2010).
14.Miller,J.C.et al.A TALE nuclease architecture for efficient genome editing. Nat Biotechnol 29,143−148(2011).
15.Mussolino,C. et al.A novel TALE nuclease scaffold enables high genome editing activity in combination with low toxicity.Nucleic acids research 39,9283−9293(2011).
16.Hsu,P.D.&Zhang,F.Dissecting neural function using targeted genome engineering technologies.ACS chemical neuroscience 3,603−610(2012).
17.Sanjana,N.E.et al.A transcription activator−like effector toolbox for genome engineering.Nature protocols 7,171−192(2012).
18.Porteus,M.H.&Baltimore,D.Chimeric nucleases stimulate gene targeting in human cells.Science 300,763(2003).
19.Miller,J.C.et al.An improved zinc−finger nuclease architecture for highly specific genome editing.Nat Biotechnol 25,778−785(2007).
20.Sander,J.D.et al.Selection−free zinc−finger−nuclease engineering by context−dependent assembly(CoDA).Nat Methods 8,67−69(2011).
21.Wood,A.J.et al.Targeted genome editing across species using ZFNs and TALENs.Science 333,307(2011).
22.Bobis−Wozowicz,S.,Osiak,A.,Rahman,S.H.&Cathomen,T.Targeted genome editing in pluripotent stem cells using zinc−finger nucleases.Methods 53,339−346(2011).
23.Jiang,W.,Bikard,D.,Cox,D.,Zhang,F.&Marraffini,L.A.RNA−guided editing of bacterial genomes using CRISPR−Cas systems.Nat Biotechnol 31,233−239(2013).
24.Qi,L.S.et al.Repurposing CRISPR as an RNA−Guided Platform for Sequence−Specific Control of Gene Expression.Cell 152,1173−1183(2013).
25.Michaelis,L.M.,Maud“Die kinetik der invertinwirkung.”.Biochem.z(1913).
26.Mahfouz,M.M.et al.De novo−engineered transcription activator−like effector (TALE)hybrid nuclease with novel DNA binding specificity creates double−strand breaks.Proc Natl Acad Sci U S A 108,2623−2628(2011).
27.Wilson,E.B.Probable inference,the law of succession,and statistical inference.J Am Stat Assoc 22, 209−212(1927).
28.Ding,Q.et al.A TALEN genome−editing system for generating human stem cell−based disease models.Cell Stem Cell 12,238−251(2013).
29.Soldner,F.et al.Generation of isogenic pluripotent stem cells differing exclusively at two early onset Parkinson point mutations.Cell 146,318−331(2011).
30.Carlson,D.F.et al.Efficient TALEN−mediated gene knockout in livestock.Proc Natl Acad Sci U S A 109,17382−17387(2012).
31.Geurts,A.M.et al.Knockout Rats via Embryo Microinjection of Zinc−Finger Nucleases.Science 325,433−433(2009).
32.Takasu,Y.et al.Targeted mutagenesis in the silkworm Bombyx mori using zinc finger nuclease mRNA injection.Insect Biochem Molec 40,759−765(2010).
33.Watanabe,T.et al.Non−transgenic genome modifications in a hemimetabolous insect using zinc−finger and TAL effector nucleases.Nat Commun 3(2012).
34.Reyon,D.et al.FLASH assembly of TALENs for high−throughput genome editing. Nat Biotechnol 30,460−465(2012).
35.Boch,J.et al.Breaking the code of DNA binding specificity of TAL−type III effectors.Science 326,1509−1512(2009).
36.Moscou,M.J.&Bogdanove,A.J.A simple cipher governs DNA recognition by TAL effectors.Science 326,1501(2009).
37.Deveau,H.,Garneau,J.E.&Moineau,S.CRISPR/Cas system and its role in phage−bacteria interactions. Annu Rev Microbiol 64,475−493(2010).
38.Horvath,P.&Barrangou,R.CRISPR/Cas,the immune system of bacteria and archaea.Science 327,167−170 (2010).
39.Makarova,K.S.et al.Evolution and classification of the CRISPR−Cas systems.Nat Rev Microbiol 9,467−477(2011).
40.Bhaya,D.,Davison,M.&Barrangou,R.CRISPR−Cas systems in bacteria and archaea:versatile small RNAs for adaptive defense and regulation.Annu Rev Genet 45,273−297(2011).
41.Garneau,J.E.et al.The CRISPR/Cas bacterial immune system cleaves bacteriophage and plasmid DNA.Nature 468,67−71(2010).
42.Gasiunas,G.,Barrangou,R.,Horvath,P.&Siksnys,V.Cas9−crRNA ribonucleoprotein complex mediates specific DNA cleavage for adaptive immunity in bacteria.Proc Natl Acad Sci U S A 109,E2579−2586 (2012).
43.Urnov,F.D.,Rebar,E.J.,Holmes,M.C., Zhang, H.S.&Gregory,P.D.Genome editing with engineered zinc finger nucleases.Nat Rev Genet 11,636−646(2010).
44.Perez,E.E.et al.Establishment of HIV−1 resistance in CD4(+)T cells by genome editing using zinc−finger nucleases.Nat Biotechnol 26,808−816(2008).
45.Chen,F.Q.et al.High−frequency genome editing using ssDNA oligonucleotides with zinc−finger nucleases.Nat Methods 8,753−U796(2011).
46.Bedell,V.M.et al.In vivo genome editing using a high−efficiency TALEN system.Nature 491,114−U133(2012).
47.Saleh−Gohari,N.&Helleday,T.Conservative homologous recombination preferentially repairs DNA double−strand breaks in the S phase of the cell cycle in human cells.Nucleic Acids Res 32,3683−3688(2004).
48.Sapranauskas,R.et al.The Streptococcus thermophilus CRISPR/Cas system provides immunity in Escherichia coli.Nucleic Acids Res 39,9275−9282 (2011).
49.Shen,B.et al.Generation of gene−modified mice via Cas9/RNA−mediated gene targeting.Cell Res 23, 720−723 (2013).
50.Tuschl,T.Expanding small RNA interference.Nat Biotechnol 20,446−448(2002).
51.Smithies,O.,Gregg,R.G.,Boggs,S.S.,Koralewski,M.A.&Kucherlapati,R.S.Insertion of DNA sequences into the human chromosomal beta−globin locus by homologous recombination.Nature 317,230−234(1985).
52.Thomas,K.R.,Folger,K.R.&Capecchi, M.R. High frequency targeting of genes to specific sites in the mammalian genome.Cell 44,419−428(1986).
53.Hasty,P.,Rivera−Perez,J.&Bradley,A.The length of homology required for gene targeting in embryonic stem cells.Mol Cell Biol 11,5586−5591(1991).
54.Wu,S.,Ying,G.X.,Wu,Q.&Capecchi,M.R.A protocol for constructing gene targeting vectors:generating knockout mice for the cadherin family and beyond.Nat Protoc 3,1056−1076(2008).
55.Oliveira,T.Y.et al.Translocation capture sequencing: a method for high throughput mapping of chromosomal rearrangements.J Immunol Methods 375,176−181 (2012).
56.Tremblay et al.,Transcription Activator−Like Effector Proteins Induce the Expression of the Frataxin Gene;Human Gene Therapy.August 2012,23(8):883−890.
57.Shalek et al.Nanowire−mediated delivery enables functional interrogation of primary immune cells:application to the analysis of chronic lymphocytic leukemia.Nano Letters,2012,Dec 12;12(12):6498−504.
58.Pardridge et al. Preparation of Trojan horse liposomes(THLs)for gene transfer across the blood−brain barrier;Cold Spring Harb Protoc;2010;Apr;2010(4)
59.Plosker GL et al.Fluvastatin:a review of its pharmacology and use in the management of hypercholesterolaemia;Drugs 1996,51(3):433−459).
60.Trapani et al.Potential role of nonstatin cholesterol lowering agents;IUBMB Life,Volume 63,Issue 11,pages 964−971,November 2011
61.Birch AM et al.DGAT1 inhibitors as anti−obesity and anti−diabetic agents;Current Opinion in Drug Discovery&Development,2010,13(4):489−496
62.Fuchs et al.Killing of leukemic cells with a BCR/ABL fusion gene by RNA interference(RNAi),Oncogene 2002,21(37):5716−5724.
63. McManaman JL et al. Perilipin−2 Null Mice are Protected Against Diet−Induced Obesity,Adipose Inflammation and Fatty Liver Disease;The Journal of Lipid Research,jlr.M035063.First Published on February 12,2013.
64.Tang J et al.Inhibition of SREBP by a Small Molecule,Betulin,Improves Hyperlipidemia and Insulin Resistance and Reduces Atherosclerotic Plaques;Cell Metabolism,Volume 13,Issue 1,44−56,5 January 2011.
65.Dumitrache et al.Trex2 enables spontaneous sister chromatid exchanges without facilitating DNA double−strand break repair;Genetics.2011 August;188(4):787−797
Claims (20)
- CRISPR複合体を含む組成物であって、
前記CRISPR複合体が、
I. CRISPR−Cas系ポリヌクレオチド配列(複数の場合も有り)であって、
(a)RNAを含み、真核細胞中の標的配列にハイブリダイズすることができ、前記標的配列への前記CRISPR複合体の配列特異的結合を指向することができる、エンジニアリングされたガイド配列、
(b)RNAを含み、tracr配列にハイブリダイズすることができる、tracrメイト配列、及び
(c)RNAを含むtracr配列
を含む、CRISPR−Cas系ポリヌクレオチド配列、並びに
II. 黄色ブドウ球菌(Staphylococcus aureus)由来のII型Cas9タンパク質であって、前記II型Cas9タンパク質が、1つ以上の核局在化配列(NLS)を含む、II型Cas9タンパク質
を含む、
組成物。 - 前記tracrメイト配列が、前記tracr配列にハイブリダイズし、前記ガイド配列が、標的配列へのCRISPR複合体の配列特異的結合を指向し、
前記CRISPR複合体が、前記II型Cas9タンパク質であって、(1)前記標的配列にハイブリダイズされる前記ガイド配列及び(2)前記tracr配列にハイブリダイズされる前記tracrメイト配列と複合体形成している、前記II型Cas9タンパク質を含む、
請求項1に記載の組成物。 - 前記CRISPR−Cas系ポリヌクレオチド配列が、キメラRNA(chiRNA)である、請求項1に記載の組成物。
- ナノ粒子、リポソーム、エキソソーム、酵母系又はマイクロベシクルを含む、請求項1〜3のいずれか一項に記載の組成物。
- 1つ以上のベクターを含むベクター系を含む組成物であって、前記1つ以上のベクターが、以下のCRISPR複合体成分:
I. CRISPR−Cas系ポリヌクレオチド配列(複数の場合も有り)であって、
(a)RNAを含み、真核細胞中の標的配列にハイブリダイズすることができ、前記標的配列への前記CRISPR複合体の配列特異的結合を指向することができる、エンジニアリングされたガイド配列、
(b)RNAを含み、tracr配列にハイブリダイズすることができる、tracrメイト配列、及び
(c)RNAを含むtracr配列
を含む、CRISPR−Cas系ポリヌクレオチド配列、並びに
II. 黄色ブドウ球菌(Staphylococcus aureus)由来のII型Cas9タンパク質であって、前記II型Cas9タンパク質が、1つ以上の核局在化配列(NLS)を含む、II型Cas9タンパク質
をコードするポリヌクレオチド配列を含む、組成物。 - 前記1つ以上のベクターが、1つ以上のウイルスベクターを含む、請求項5に記載の組成物。
- 前記1つ以上のウイルスベクターが、1つ以上のレトロウイルス、レンチウイルス、アデノウイルス、アデノ随伴ウイルス又は単純ヘルペスウイルスベクターを含む、請求項6に記載の組成物。
- 前記組成物が、単一ベクターを含む、請求項5〜7のいずれか一項に記載の組成物。
- 前記II型Cas9タンパク質をコードする前記ポリヌクレオチド配列が、真核細胞中の発現のためにコドン最適化されている、請求項5〜8のいずれか一項に記載の組成物。
- 組織特異的プロモーターが、筋肉、ニューロン、骨、皮膚、血液、肝臓、膵臓又はリンパ球における前記CRISPR複合体成分の発現を指図する、請求項5〜9のいずれか一項に記載の組成物。
- 前記tracr配列が、30以上のヌクレオチドの長さを有する、請求項1〜10のいずれか一項に記載の組成物。
- 前記tracr配列が、50以上のヌクレオチドの長さを有する、請求項1〜11のいずれか一項に記載の組成物。
- 前記II型Cas9タンパク質が、2つ以上の核局在化配列(NLS)を含む、請求項1〜12のいずれか一項に記載の組成物。
- 前記組成物が、ゲノムエンジニアリングのためのものである、請求項1〜13のいずれか一項に記載の組成物。
- 請求項1〜14のいずれか一項に記載の組成物を含む、エクスビボ又はインビトロ宿主細胞又は細胞系であって、前記宿主細胞又は細胞系が、ヒト生殖系列細胞ではない、エクスビボ又はインビトロ宿主細胞又は細胞系。
- 幹細胞又は幹細胞系である、請求項15に記載のエクスビボ又はインビトロ宿主細胞又は細胞系。
- 目的のゲノム遺伝子座での1つ以上の標的配列の操作によって真核生物を改変する方法であって、前記方法が、請求項1〜14のいずれか一項に記載の組成物を前記生物に送達することを含み、前記真核生物が、非ヒト生物である、方法。
- 目的のゲノム遺伝子座での1つ以上の標的配列の操作によって真核生物の細胞を改変するエクスビボ方法であって、前記方法が、請求項1〜14のいずれか一項に記載の組成物を前記細胞に送達することを含み、前記方法が、人間の生殖系列の遺伝的アイデンティティを改変するためのプロセスを含まない、方法。
- 前記生物が、植物である、請求項17又は18に記載の方法。
- エクスビボ遺伝子又はゲノム編集における請求項1〜14のいずれか一項に記載の組成物の使用であって、前記使用が、人間の生殖系列の遺伝的アイデンティティを改変するためのプロセスを含まず、前記使用は、人体における疾患の治療又は予防のための方法ではなく、前記使用は、前記系を人体に投与する工程を含まない、使用。
Applications Claiming Priority (24)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201261736527P | 2012-12-12 | 2012-12-12 | |
US61/736,527 | 2012-12-12 | ||
US201361748427P | 2013-01-02 | 2013-01-02 | |
US61/748,427 | 2013-01-02 | ||
US201361758468P | 2013-01-30 | 2013-01-30 | |
US61/758,468 | 2013-01-30 | ||
US201361769046P | 2013-02-25 | 2013-02-25 | |
US61/769,046 | 2013-02-25 | ||
US201361791409P | 2013-03-15 | 2013-03-15 | |
US201361802174P | 2013-03-15 | 2013-03-15 | |
US61/791,409 | 2013-03-15 | ||
US61/802,174 | 2013-03-15 | ||
US201361806375P | 2013-03-28 | 2013-03-28 | |
US61/806,375 | 2013-03-28 | ||
US201361814263P | 2013-04-20 | 2013-04-20 | |
US61/814,263 | 2013-04-20 | ||
US201361819803P | 2013-05-06 | 2013-05-06 | |
US61/819,803 | 2013-05-06 | ||
US201361828130P | 2013-05-28 | 2013-05-28 | |
US61/828,130 | 2013-05-28 | ||
US201361835931P | 2013-06-17 | 2013-06-17 | |
US201361836101P | 2013-06-17 | 2013-06-17 | |
US61/835,931 | 2013-06-17 | ||
US61/836,101 | 2013-06-17 |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2016131404A Division JP6395765B2 (ja) | 2012-12-12 | 2016-07-01 | 配列操作のための改善された系、方法および酵素組成物のエンジニアリングおよび最適化 |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2020025253A Division JP7125440B2 (ja) | 2012-12-12 | 2020-02-18 | 配列操作のための改善された系、方法および酵素組成物のエンジニアリングおよび最適化 |
Publications (3)
Publication Number | Publication Date |
---|---|
JP2018143253A true JP2018143253A (ja) | 2018-09-20 |
JP2018143253A5 JP2018143253A5 (ja) | 2019-05-16 |
JP6665230B2 JP6665230B2 (ja) | 2020-03-13 |
Family
ID=49883291
Family Applications (5)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2015547545A Active JP6552965B2 (ja) | 2012-12-12 | 2013-12-12 | 配列操作のための改善された系、方法および酵素組成物のエンジニアリングおよび最適化 |
JP2016131404A Active JP6395765B2 (ja) | 2012-12-12 | 2016-07-01 | 配列操作のための改善された系、方法および酵素組成物のエンジニアリングおよび最適化 |
JP2018119670A Active JP6665230B2 (ja) | 2012-12-12 | 2018-06-25 | 配列操作のための改善された系、方法および酵素組成物のエンジニアリングおよび最適化 |
JP2020025253A Active JP7125440B2 (ja) | 2012-12-12 | 2020-02-18 | 配列操作のための改善された系、方法および酵素組成物のエンジニアリングおよび最適化 |
JP2022092414A Pending JP2022113766A (ja) | 2012-12-12 | 2022-06-07 | 配列操作のための改善された系、方法および酵素組成物のエンジニアリングおよび最適化 |
Family Applications Before (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2015547545A Active JP6552965B2 (ja) | 2012-12-12 | 2013-12-12 | 配列操作のための改善された系、方法および酵素組成物のエンジニアリングおよび最適化 |
JP2016131404A Active JP6395765B2 (ja) | 2012-12-12 | 2016-07-01 | 配列操作のための改善された系、方法および酵素組成物のエンジニアリングおよび最適化 |
Family Applications After (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2020025253A Active JP7125440B2 (ja) | 2012-12-12 | 2020-02-18 | 配列操作のための改善された系、方法および酵素組成物のエンジニアリングおよび最適化 |
JP2022092414A Pending JP2022113766A (ja) | 2012-12-12 | 2022-06-07 | 配列操作のための改善された系、方法および酵素組成物のエンジニアリングおよび最適化 |
Country Status (16)
Country | Link |
---|---|
US (5) | US20140186919A1 (ja) |
EP (1) | EP2898075B1 (ja) |
JP (5) | JP6552965B2 (ja) |
KR (1) | KR20150105634A (ja) |
CN (2) | CN113355357A (ja) |
AU (4) | AU2013359212B2 (ja) |
CA (1) | CA2894684A1 (ja) |
DK (2) | DK3064585T3 (ja) |
ES (2) | ES2576126T3 (ja) |
HK (1) | HK1207119A1 (ja) |
IL (2) | IL300461A (ja) |
PL (1) | PL2898075T3 (ja) |
PT (1) | PT2898075E (ja) |
SG (3) | SG10201912327SA (ja) |
WO (1) | WO2014093635A1 (ja) |
ZA (1) | ZA201504081B (ja) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPWO2020067004A1 (ja) * | 2018-09-25 | 2021-08-30 | 公益財団法人微生物化学研究会 | 新規ウイルスベクターおよびその製造方法と使用方法 |
Families Citing this family (610)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2011002988A1 (en) | 2009-07-01 | 2011-01-06 | Transposagen Biopharmaceuticals, Inc. | Genetically modified rat models for severe combined immunodeficiency (scid) |
EP3613852A3 (en) | 2011-07-22 | 2020-04-22 | President and Fellows of Harvard College | Evaluation and improvement of nuclease cleavage specificity |
GB201117313D0 (en) | 2011-10-07 | 2011-11-16 | Gt Biolog Ltd | Bacterium for use in medicine |
GB201122458D0 (en) | 2011-12-30 | 2012-02-08 | Univ Wageningen | Modified cascade ribonucleoproteins and uses thereof |
WO2013139861A1 (en) | 2012-03-20 | 2013-09-26 | Luc Montagnier | Methods and pharmaceutical compositions of the treatment of autistic syndrome disorders |
WO2013163394A1 (en) | 2012-04-25 | 2013-10-31 | Regeneron Pharmaceuticals, Inc. | Nuclease-mediated targeting with large targeting vectors |
DK3401400T3 (da) | 2012-05-25 | 2019-06-03 | Univ California | Fremgangsmåder og sammensætninger til rna-styret mål-dna-modifikation og til rna-styret transskriptionsmodulering |
ES2613691T3 (es) | 2012-07-11 | 2017-05-25 | Sangamo Biosciences, Inc. | Métodos y composiciones para el tratamiento de enfermedades por almacenamiento lisosomal |
US10648001B2 (en) | 2012-07-11 | 2020-05-12 | Sangamo Therapeutics, Inc. | Method of treating mucopolysaccharidosis type I or II |
JP2015527889A (ja) * | 2012-07-25 | 2015-09-24 | ザ ブロード インスティテュート, インコーポレイテッド | 誘導可能なdna結合タンパク質およびゲノム撹乱ツール、ならびにそれらの適用 |
CN110643600A (zh) | 2012-10-23 | 2020-01-03 | 基因工具股份有限公司 | 用于切割靶dna的系统及其用途 |
JP6620018B2 (ja) | 2012-12-06 | 2019-12-11 | シグマ−アルドリッチ・カンパニー・リミテッド・ライアビリティ・カンパニーSigma−Aldrich Co., LLC | Crisprに基づくゲノム修飾および制御 |
US8697359B1 (en) | 2012-12-12 | 2014-04-15 | The Broad Institute, Inc. | CRISPR-Cas systems and methods for altering expression of gene products |
WO2014093709A1 (en) | 2012-12-12 | 2014-06-19 | The Broad Institute, Inc. | Methods, models, systems, and apparatus for identifying target sequences for cas enzymes or crispr-cas systems for target sequences and conveying results thereof |
US20140186843A1 (en) | 2012-12-12 | 2014-07-03 | Massachusetts Institute Of Technology | Methods, systems, and apparatus for identifying target sequences for cas enzymes or crispr-cas systems for target sequences and conveying results thereof |
MX2015007550A (es) | 2012-12-12 | 2017-02-02 | Broad Inst Inc | Suministro, modificación y optimización de sistemas, métodos y composiciones para la manipulación de secuencias y aplicaciones terapéuticas. |
US8993233B2 (en) | 2012-12-12 | 2015-03-31 | The Broad Institute Inc. | Engineering and optimization of systems, methods and compositions for sequence manipulation with functional domains |
PT2898075E (pt) * | 2012-12-12 | 2016-06-16 | Harvard College | Manipulação e otimização de sistemas, métodos e composições de enzima melhorados para manipulação de sequências |
CN105658796B (zh) | 2012-12-12 | 2021-10-26 | 布罗德研究所有限公司 | 用于序列操纵的crispr-cas组分系统、方法以及组合物 |
EP3553174A1 (en) | 2012-12-17 | 2019-10-16 | President and Fellows of Harvard College | Rna-guided human genome engineering |
CN113005148A (zh) | 2013-01-16 | 2021-06-22 | 爱默蕾大学 | Cas9-核酸复合物及其相关用途 |
CN109913495B (zh) | 2013-02-20 | 2022-11-25 | 瑞泽恩制药公司 | 大鼠的遗传修饰 |
EP2971167B1 (en) | 2013-03-14 | 2019-07-31 | Caribou Biosciences, Inc. | Compositions and methods of nucleic acid-targeting nucleic acids |
CA2907198C (en) | 2013-03-15 | 2019-12-10 | The General Hospital Corporation | Using rna-guided foki nucleases (rfns) to increase specificity for rna-guided genome editing |
US10760064B2 (en) | 2013-03-15 | 2020-09-01 | The General Hospital Corporation | RNA-guided targeting of genetic and epigenomic regulatory proteins to specific genomic loci |
WO2014204578A1 (en) | 2013-06-21 | 2014-12-24 | The General Hospital Corporation | Using rna-guided foki nucleases (rfns) to increase specificity for rna-guided genome editing |
US9234213B2 (en) | 2013-03-15 | 2016-01-12 | System Biosciences, Llc | Compositions and methods directed to CRISPR/Cas genomic engineering systems |
CN105518146B (zh) | 2013-04-04 | 2022-07-15 | 哈佛学院校长同事会 | 利用CRISPR/Cas系统的基因组编辑的治疗性用途 |
GB201306536D0 (en) | 2013-04-10 | 2013-05-22 | Gt Biolog Ltd | Polypeptide and immune modulation |
CN111500630A (zh) | 2013-04-16 | 2020-08-07 | 瑞泽恩制药公司 | 大鼠基因组的靶向修饰 |
US20160186208A1 (en) * | 2013-04-16 | 2016-06-30 | Whitehead Institute For Biomedical Research | Methods of Mutating, Modifying or Modulating Nucleic Acid in a Cell or Nonhuman Mammal |
WO2014186686A2 (en) * | 2013-05-17 | 2014-11-20 | Two Blades Foundation | Targeted mutagenesis and genome engineering in plants using rna-guided cas nucleases |
US11685935B2 (en) * | 2013-05-29 | 2023-06-27 | Cellectis | Compact scaffold of Cas9 in the type II CRISPR system |
US20150067922A1 (en) * | 2013-05-30 | 2015-03-05 | The Penn State Research Foundation | Gene targeting and genetic modification of plants via rna-guided genome editing |
JP6702858B2 (ja) | 2013-06-17 | 2020-06-03 | ザ・ブロード・インスティテュート・インコーポレイテッド | ウイルス成分を使用して障害および疾患をターゲティングするためのCRISPR−Cas系および組成物の送達、使用および治療上の適用 |
EP3011029B1 (en) | 2013-06-17 | 2019-12-11 | The Broad Institute, Inc. | Delivery, engineering and optimization of tandem guide systems, methods and compositions for sequence manipulation |
EP3725885A1 (en) | 2013-06-17 | 2020-10-21 | The Broad Institute, Inc. | Functional genomics using crispr-cas systems, compositions methods, screens and applications thereof |
AU2014281028B2 (en) | 2013-06-17 | 2020-09-10 | Massachusetts Institute Of Technology | Delivery and use of the CRISPR-Cas systems, vectors and compositions for hepatic targeting and therapy |
EP4245853A3 (en) | 2013-06-17 | 2023-10-18 | The Broad Institute, Inc. | Optimized crispr-cas double nickase systems, methods and compositions for sequence manipulation |
JP2016528890A (ja) | 2013-07-09 | 2016-09-23 | プレジデント アンド フェローズ オブ ハーバード カレッジ | CRISPR/Cas系を用いるゲノム編集の治療用の使用 |
EP3019204B1 (en) | 2013-07-10 | 2020-01-01 | President and Fellows of Harvard College | Orthogonal cas9 proteins for rna-guided gene regulation and editing |
US10563225B2 (en) | 2013-07-26 | 2020-02-18 | President And Fellows Of Harvard College | Genome engineering |
US20150044192A1 (en) | 2013-08-09 | 2015-02-12 | President And Fellows Of Harvard College | Methods for identifying a target site of a cas9 nuclease |
WO2015026887A1 (en) * | 2013-08-22 | 2015-02-26 | E. I. Du Pont De Nemours And Company | A soybean u6 polymerase iii promoter and methods of use |
US9359599B2 (en) | 2013-08-22 | 2016-06-07 | President And Fellows Of Harvard College | Engineered transcription activator-like effector (TALE) domains and uses thereof |
AU2014312123A1 (en) | 2013-08-29 | 2016-03-17 | Temple University Of The Commonwealth System Of Higher Education | Methods and compositions for RNA-guided treatment of HIV infection |
US9322037B2 (en) | 2013-09-06 | 2016-04-26 | President And Fellows Of Harvard College | Cas9-FokI fusion proteins and uses thereof |
US9737604B2 (en) | 2013-09-06 | 2017-08-22 | President And Fellows Of Harvard College | Use of cationic lipids to deliver CAS9 |
US9228207B2 (en) | 2013-09-06 | 2016-01-05 | President And Fellows Of Harvard College | Switchable gRNAs comprising aptamers |
ES2681622T3 (es) | 2013-09-18 | 2018-09-14 | Kymab Limited | Métodos, células y organismos |
WO2015054507A1 (en) | 2013-10-10 | 2015-04-16 | Pronutria, Inc. | Nutritive polypeptide production systems, and methods of manufacture and use thereof |
WO2015065964A1 (en) | 2013-10-28 | 2015-05-07 | The Broad Institute Inc. | Functional genomics using crispr-cas systems, compositions, methods, screens and applications thereof |
US9834791B2 (en) | 2013-11-07 | 2017-12-05 | Editas Medicine, Inc. | CRISPR-related methods and compositions with governing gRNAS |
EP3071695A2 (en) * | 2013-11-18 | 2016-09-28 | Crispr Therapeutics AG | Crispr-cas system materials and methods |
US9074199B1 (en) * | 2013-11-19 | 2015-07-07 | President And Fellows Of Harvard College | Mutant Cas9 proteins |
US9546384B2 (en) | 2013-12-11 | 2017-01-17 | Regeneron Pharmaceuticals, Inc. | Methods and compositions for the targeted modification of a mouse genome |
KR20160089530A (ko) | 2013-12-12 | 2016-07-27 | 더 브로드 인스티튜트, 인코퍼레이티드 | Hbv 및 바이러스 질병 및 질환을 위한 crisprcas 시스템 및 조성물의 전달,용도 및 치료적 적용 |
WO2015089419A2 (en) | 2013-12-12 | 2015-06-18 | The Broad Institute Inc. | Delivery, use and therapeutic applications of the crispr-cas systems and compositions for targeting disorders and diseases using particle delivery components |
CN111206032A (zh) | 2013-12-12 | 2020-05-29 | 布罗德研究所有限公司 | 用于基因组编辑的crispr-cas系统和组合物的递送、用途和治疗应用 |
SG10201804973TA (en) | 2013-12-12 | 2018-07-30 | Broad Inst Inc | Compositions and Methods of Use of Crispr-Cas Systems in Nucleotide Repeat Disorders |
CN105899657A (zh) | 2013-12-12 | 2016-08-24 | 布罗德研究所有限公司 | 用于改变基因产物表达的crispr-cas系统和方法、结构信息以及诱导型模块化cas酶 |
EP3080271B1 (en) | 2013-12-12 | 2020-02-12 | The Broad Institute, Inc. | Systems, methods and compositions for sequence manipulation with optimized functional crispr-cas systems |
US9068179B1 (en) | 2013-12-12 | 2015-06-30 | President And Fellows Of Harvard College | Methods for correcting presenilin point mutations |
WO2015089364A1 (en) | 2013-12-12 | 2015-06-18 | The Broad Institute Inc. | Crystal structure of a crispr-cas system, and uses thereof |
WO2015089473A1 (en) | 2013-12-12 | 2015-06-18 | The Broad Institute Inc. | Engineering of systems, methods and optimized guide compositions with new architectures for sequence manipulation |
CA3225453A1 (en) | 2013-12-19 | 2015-06-25 | Novartis Ag | Human mesothelin chimeric antigen receptors and uses thereof |
MX2016010285A (es) | 2014-02-11 | 2017-01-11 | Univ Colorado Regents | Ingenieria genetica multiplexada habilitada por crispr. |
RU2016136977A (ru) * | 2014-02-18 | 2018-03-20 | Дьюк Юниверсити | Композиции для инактивации репликации вируса и способы их получения и применения |
CN106232803A (zh) | 2014-02-27 | 2016-12-14 | 孟山都技术公司 | 用于定点基因组修饰的组合物和方法 |
AU2015222944A1 (en) | 2014-02-27 | 2016-09-08 | Massachusetts Institute Of Technology | T cell balance gene expression, compositions of matters and methods of use thereof |
WO2015134812A1 (en) | 2014-03-05 | 2015-09-11 | Editas Medicine, Inc. | Crispr/cas-related methods and compositions for treating usher syndrome and retinitis pigmentosa |
DK3116997T3 (da) | 2014-03-10 | 2019-08-19 | Editas Medicine Inc | Crispr/cas-relaterede fremgangsmåder og sammensætninger til behandling af lebers kongenitale amaurose 10 (lca10) |
US11339437B2 (en) | 2014-03-10 | 2022-05-24 | Editas Medicine, Inc. | Compositions and methods for treating CEP290-associated disease |
US11141493B2 (en) | 2014-03-10 | 2021-10-12 | Editas Medicine, Inc. | Compositions and methods for treating CEP290-associated disease |
JP2017513818A (ja) | 2014-03-15 | 2017-06-01 | ノバルティス アーゲー | キメラ抗原受容体を使用する癌の処置 |
US11242525B2 (en) | 2014-03-26 | 2022-02-08 | Editas Medicine, Inc. | CRISPR/CAS-related methods and compositions for treating sickle cell disease |
WO2015153789A1 (en) * | 2014-04-01 | 2015-10-08 | Editas Medicine, Inc. | Crispr/cas-related methods and compositions for treating herpes simplex virus type 1 (hsv-1) |
HUE054588T2 (hu) | 2014-04-07 | 2021-09-28 | Novartis Ag | Rák kezelése CD19 elleni, kiméra antigénreceptor alkalmazásával |
WO2015157070A2 (en) | 2014-04-09 | 2015-10-15 | Editas Medicine, Inc. | Crispr/cas-related methods and compositions for treating cystic fibrosis |
BR112016028023A2 (pt) | 2014-05-30 | 2017-08-22 | Univ Leland Stanford Junior | Composições e métodos de administração de tratamentos para infecções virais latentes |
CN113215196A (zh) | 2014-06-06 | 2021-08-06 | 瑞泽恩制药公司 | 用于修饰所靶向基因座的方法和组合物 |
AU2015274367B2 (en) | 2014-06-13 | 2020-11-26 | Beth Israel Deaconess Medical Center, Inc. | Products and methods to isolate mitochondria |
AU2015280069B2 (en) | 2014-06-23 | 2021-08-12 | The General Hospital Corporation | Genomewide unbiased identification of dsbs evaluated by sequencing (guide-seq) |
HUE041584T2 (hu) | 2014-06-26 | 2019-05-28 | Regeneron Pharma | Célzott genetikai módosítások és alkalmazási módszerek és készítmények |
US10676754B2 (en) | 2014-07-11 | 2020-06-09 | E I Du Pont De Nemours And Company | Compositions and methods for producing plants resistant to glyphosate herbicide |
CN104152414B (zh) * | 2014-07-18 | 2018-03-13 | 中国科学院广州生物医药与健康研究院 | 对细胞基因组的预定位点进行基因改造的方法 |
US11542488B2 (en) | 2014-07-21 | 2023-01-03 | Novartis Ag | Sortase synthesized chimeric antigen receptors |
CA2955154C (en) | 2014-07-21 | 2023-10-31 | Novartis Ag | Treatment of cancer using a cd33 chimeric antigen receptor |
EP3193915A1 (en) | 2014-07-21 | 2017-07-26 | Novartis AG | Combinations of low, immune enhancing. doses of mtor inhibitors and cars |
MY181834A (en) | 2014-07-21 | 2021-01-08 | Novartis Ag | Treatment of cancer using humanized anti-bcma chimeric antigen receptor |
AU2015298571B2 (en) | 2014-07-30 | 2020-09-03 | President And Fellows Of Harvard College | Cas9 proteins including ligand-dependent inteins |
EP4205749A1 (en) | 2014-07-31 | 2023-07-05 | Novartis AG | Subset-optimized chimeric antigen receptor-containing cells |
EP4194557A1 (en) * | 2014-08-06 | 2023-06-14 | Institute for Basic Science | Genome editing using campylobacter jejuni crispr/cas system-derived rgen |
JP6837429B2 (ja) * | 2014-08-11 | 2021-03-03 | ザ ボード オブ リージェンツ オブ ザ ユニバーシティー オブ テキサス システム | Crispr/cas9媒介遺伝子編集による筋ジストロフィーの予防 |
CA2958200A1 (en) | 2014-08-14 | 2016-02-18 | Novartis Ag | Treatment of cancer using a gfr alpha-4 chimeric antigen receptor |
WO2016028682A1 (en) * | 2014-08-17 | 2016-02-25 | The Broad Institute Inc. | Genome editing using cas9 nickases |
PL3183268T3 (pl) | 2014-08-19 | 2020-09-07 | Novartis Ag | Chimeryczny receptor antygenowy (CAR) anty-CD123 do zastosowania w leczeniu nowotworu złośliwego |
NZ728437A (en) | 2014-08-27 | 2018-02-23 | Caribou Biosciences Inc | Methods for increasing cas9-mediated engineering efficiency |
WO2016036754A1 (en) | 2014-09-02 | 2016-03-10 | The Regents Of The University Of California | Methods and compositions for rna-directed target dna modification |
CN108064129A (zh) | 2014-09-12 | 2018-05-22 | 纳幕尔杜邦公司 | 玉米和大豆中复合性状基因座的位点特异性整合位点的产生和使用方法 |
WO2016044605A1 (en) | 2014-09-17 | 2016-03-24 | Beatty, Gregory | Targeting cytotoxic cells with chimeric receptors for adoptive immunotherapy |
WO2016049163A2 (en) | 2014-09-24 | 2016-03-31 | The Broad Institute Inc. | Use and production of chd8+/- transgenic animals with behavioral phenotypes characteristic of autism spectrum disorder |
WO2016049251A1 (en) | 2014-09-24 | 2016-03-31 | The Broad Institute Inc. | Delivery, use and therapeutic applications of the crispr-cas systems and compositions for modeling mutations in leukocytes |
WO2016049024A2 (en) | 2014-09-24 | 2016-03-31 | The Broad Institute Inc. | Delivery, use and therapeutic applications of the crispr-cas systems and compositions for modeling competition of multiple cancer mutations in vivo |
WO2016049258A2 (en) | 2014-09-25 | 2016-03-31 | The Broad Institute Inc. | Functional screening with optimized functional crispr-cas systems |
US10040048B1 (en) | 2014-09-25 | 2018-08-07 | Synthego Corporation | Automated modular system and method for production of biopolymers |
US20160090603A1 (en) * | 2014-09-30 | 2016-03-31 | Sandia Corporation | Delivery platforms for the domestication of algae and plants |
CN104546931B (zh) * | 2014-09-30 | 2019-04-09 | 深圳华大基因科技有限公司 | 华德萨特氏菌在治疗或预防类风湿性关节炎或其相关疾病中的应用 |
CA2964234A1 (en) * | 2014-10-10 | 2016-04-14 | Massachusetts Eye And Ear Infirmary | Efficient delivery of therapeutic molecules in vitro and in vivo |
EP3212788A2 (en) | 2014-10-27 | 2017-09-06 | The Broad Institute, Inc. | Compositions, methods and use of synthetic lethal screening |
CA2963820A1 (en) | 2014-11-07 | 2016-05-12 | Editas Medicine, Inc. | Methods for improving crispr/cas-mediated genome-editing |
EP3222728B1 (en) * | 2014-11-19 | 2021-07-14 | Institute for Basic Science | Method for regulating gene expression using cas9 protein expressed from two vectors |
US10362771B2 (en) | 2014-11-20 | 2019-07-30 | Kyoto University | Method for knock-in of DNA into target region of mammalian genome, and cell |
PT3221457T (pt) | 2014-11-21 | 2019-06-27 | Regeneron Pharma | Métodos e composições para modificação genética visada através da utilização de arn guia emparelhados |
US11168369B2 (en) | 2014-11-25 | 2021-11-09 | The Brigham And Women's Hospital, Inc. | Method of identifying and treating a person having a predisposition to or afflicted with a cardiometabolic disease |
EP3224362A4 (en) | 2014-11-26 | 2018-06-06 | The Regents of The University of California | Therapeutic compositions comprising transcription factors and methods of making and using the same |
GB201421096D0 (en) | 2014-11-27 | 2015-01-14 | Imp Innovations Ltd | Genome editing methods |
JP7068821B2 (ja) | 2014-12-03 | 2022-05-17 | アジレント・テクノロジーズ・インク | 化学修飾を有するガイドrna |
KR102656470B1 (ko) | 2014-12-10 | 2024-04-09 | 리전츠 오브 더 유니버스티 오브 미네소타 | 질환을 치료하기 위한 유전적으로 변형된 세포, 조직 및 장기 |
WO2016094874A1 (en) | 2014-12-12 | 2016-06-16 | The Broad Institute Inc. | Escorted and functionalized guides for crispr-cas systems |
WO2016094880A1 (en) * | 2014-12-12 | 2016-06-16 | The Broad Institute Inc. | Delivery, use and therapeutic applications of crispr systems and compositions for genome editing as to hematopoietic stem cells (hscs) |
WO2016094872A1 (en) | 2014-12-12 | 2016-06-16 | The Broad Institute Inc. | Dead guides for crispr transcription factors |
WO2016094867A1 (en) | 2014-12-12 | 2016-06-16 | The Broad Institute Inc. | Protected guide rnas (pgrnas) |
EP3234133B1 (en) * | 2014-12-18 | 2020-11-11 | Integrated DNA Technologies, Inc. | Crispr-based compositions and methods of use |
US20190054117A1 (en) | 2014-12-19 | 2019-02-21 | Novartis Ag | Dimerization switches and uses thereof |
WO2016100974A1 (en) | 2014-12-19 | 2016-06-23 | The Broad Institute Inc. | Unbiased identification of double-strand breaks and genomic rearrangement by genome-wide insert capture sequencing |
RU2707137C2 (ru) | 2014-12-19 | 2019-11-22 | Регенерон Фармасьютикалз, Инк. | Способы и композиции для нацеленной генетической модификации посредством одноэтапного множественного нацеливания |
HUE037476T2 (hu) | 2014-12-23 | 2018-08-28 | 4D Pharma Res Ltd | Pirin polipeptid és immunmodulálás |
US9963710B2 (en) | 2014-12-23 | 2018-05-08 | Syngenta Participations Ag | Methods and compositions for identifying and enriching for cells comprising site specific genomic modifications |
WO2016106236A1 (en) | 2014-12-23 | 2016-06-30 | The Broad Institute Inc. | Rna-targeting system |
EP3065748B1 (en) | 2014-12-23 | 2017-11-22 | 4D Pharma Research Limited | A bacteroides thetaiotaomicron strain and its use in reducing inflammation |
AU2015369725A1 (en) | 2014-12-24 | 2017-06-29 | Massachusetts Institute Of Technology | CRISPR having or associated with destabilization domains |
WO2016108926A1 (en) | 2014-12-30 | 2016-07-07 | The Broad Institute Inc. | Crispr mediated in vivo modeling and genetic screening of tumor growth and metastasis |
US11208638B2 (en) | 2015-01-12 | 2021-12-28 | The Regents Of The University Of California | Heterodimeric Cas9 and methods of use thereof |
HRP20231022T1 (hr) | 2015-01-28 | 2023-12-08 | Caribou Biosciences, Inc. | Hibridni polinukleotidi crispr dna/rna i načini uporabe |
WO2016123243A1 (en) | 2015-01-28 | 2016-08-04 | The Regents Of The University Of California | Methods and compositions for labeling a single-stranded target nucleic acid |
EP3262162A4 (en) * | 2015-02-23 | 2018-08-08 | Voyager Therapeutics, Inc. | Regulatable expression using adeno-associated virus (aav) |
WO2016138488A2 (en) | 2015-02-26 | 2016-09-01 | The Broad Institute Inc. | T cell balance gene expression, compositions of matters and methods of use thereof |
CA2977685C (en) | 2015-03-02 | 2024-02-20 | Sinai Health System | Homologous recombination factors |
CA2978314A1 (en) | 2015-03-03 | 2016-09-09 | The General Hospital Corporation | Engineered crispr-cas9 nucleases with altered pam specificity |
CN107567499A (zh) | 2015-03-27 | 2018-01-09 | 纳幕尔杜邦公司 | 大豆u6核小rna基因启动子及其在植物小rna基因的组成型表达中的用途 |
EP3277816B1 (en) * | 2015-04-01 | 2020-06-17 | Editas Medicine, Inc. | Crispr/cas-related methods and compositions for treating duchenne muscular dystrophy and becker muscular dystrophy |
AU2016246450B2 (en) | 2015-04-06 | 2022-03-17 | Agilent Technologies, Inc. | Chemically modified guide RNAs for CRISPR/Cas-mediated gene regulation |
EP3286211A1 (en) | 2015-04-23 | 2018-02-28 | Novartis AG | Treatment of cancer using chimeric antigen receptor and protein kinase a blocker |
AU2016253150B2 (en) | 2015-04-24 | 2022-04-21 | Editas Medicine, Inc. | Evaluation of Cas9 molecule/guide RNA molecule complexes |
WO2016182893A1 (en) | 2015-05-08 | 2016-11-17 | Teh Broad Institute Inc. | Functional genomics using crispr-cas systems for saturating mutagenesis of non-coding elements, compositions, methods, libraries and applications thereof |
EP3294896A1 (en) | 2015-05-11 | 2018-03-21 | Editas Medicine, Inc. | Optimized crispr/cas9 systems and methods for gene editing in stem cells |
WO2016183438A1 (en) * | 2015-05-14 | 2016-11-17 | Massachusetts Institute Of Technology | Self-targeting genome editing system |
WO2016186946A1 (en) * | 2015-05-15 | 2016-11-24 | Pioneer Hi-Bred International, Inc. | Rapid characterization of cas endonuclease systems, pam sequences and guide rna elements |
US10117911B2 (en) | 2015-05-29 | 2018-11-06 | Agenovir Corporation | Compositions and methods to treat herpes simplex virus infections |
GB2542653A (en) * | 2015-05-29 | 2017-03-29 | Agenovir Corp | Methods and compositions for treating cells for transplant |
EP3303585A4 (en) | 2015-06-03 | 2018-10-31 | Board of Regents of the University of Nebraska | Dna editing using single-stranded dna |
EP3303634B1 (en) | 2015-06-03 | 2023-08-30 | The Regents of The University of California | Cas9 variants and methods of use thereof |
EP3302525A2 (en) | 2015-06-05 | 2018-04-11 | Novartis AG | Methods and compositions for diagnosing, treating, and monitoring treatment of shank3 deficiency associated disorders |
AU2016276702B2 (en) | 2015-06-09 | 2022-07-28 | Editas Medicine, Inc. | CRISPR/CAS-related methods and compositions for improving transplantation |
PL3240554T3 (pl) | 2015-06-15 | 2020-02-28 | 4D Pharma Research Limited | Blautia stercosis i wexlerae do stosowania w leczeniu chorób zapalnych i autoimmunologicznych |
MA41060B1 (fr) | 2015-06-15 | 2019-11-29 | 4D Pharma Res Ltd | Compositions comprenant des souches bactériennes |
RS63089B1 (sr) | 2015-06-15 | 2022-04-29 | 4D Pharma Res Ltd | Kompozicije koje sadrže bakterijske sojeve |
EP3307288B1 (en) | 2015-06-15 | 2019-07-24 | 4D Pharma Research Limited | Compositions comprising bacterial strains |
MA41010B1 (fr) | 2015-06-15 | 2020-01-31 | 4D Pharma Res Ltd | Compositions comprenant des souches bactériennes |
WO2016205728A1 (en) | 2015-06-17 | 2016-12-22 | Massachusetts Institute Of Technology | Crispr mediated recording of cellular events |
JP2018518181A (ja) | 2015-06-17 | 2018-07-12 | ザ ユーエービー リサーチ ファンデーション | 血液細胞系列の細胞に機能的ポリペプチドを導入するためのCRISPR/Cas9複合体 |
CN107949641A (zh) | 2015-06-17 | 2018-04-20 | Uab研究基金会 | 用于基因组编辑的crispr/cas9复合物 |
CN108290933A (zh) | 2015-06-18 | 2018-07-17 | 布罗德研究所有限公司 | 降低脱靶效应的crispr酶突变 |
WO2016205745A2 (en) * | 2015-06-18 | 2016-12-22 | The Broad Institute Inc. | Cell sorting |
WO2016205759A1 (en) | 2015-06-18 | 2016-12-22 | The Broad Institute Inc. | Engineering and optimization of systems, methods, enzymes and guide scaffolds of cas9 orthologs and variants for sequence manipulation |
US9790490B2 (en) | 2015-06-18 | 2017-10-17 | The Broad Institute Inc. | CRISPR enzymes and systems |
EP3666895A1 (en) | 2015-06-18 | 2020-06-17 | The Broad Institute, Inc. | Novel crispr enzymes and systems |
AU2016279062A1 (en) | 2015-06-18 | 2019-03-28 | Omar O. Abudayyeh | Novel CRISPR enzymes and systems |
WO2017004261A1 (en) | 2015-06-29 | 2017-01-05 | Ionis Pharmaceuticals, Inc. | Modified crispr rna and modified single crispr rna and uses thereof |
US20170000743A1 (en) * | 2015-07-02 | 2017-01-05 | Vindico NanoBio Technology Inc. | Compositions and Methods for Delivery of Gene Editing Tools Using Polymeric Vesicles |
US10456452B2 (en) | 2015-07-02 | 2019-10-29 | Poseida Therapeutics, Inc. | Compositions and methods for improved encapsulation of functional proteins in polymeric vesicles |
EP4339287A3 (en) | 2015-07-31 | 2024-05-22 | Regents Of The University Of Minnesota | Modified cells and methods of therapy |
US9580727B1 (en) | 2015-08-07 | 2017-02-28 | Caribou Biosciences, Inc. | Compositions and methods of engineered CRISPR-Cas9 systems using split-nexus Cas9-associated polynucleotides |
WO2017027392A1 (en) | 2015-08-07 | 2017-02-16 | Novartis Ag | Treatment of cancer using chimeric cd3 receptor proteins |
WO2017027910A1 (en) | 2015-08-14 | 2017-02-23 | The University Of Sydney | Connexin 45 inhibition for therapy |
EP3337908A4 (en) | 2015-08-18 | 2019-01-23 | The Broad Institute, Inc. | METHOD AND COMPOSITIONS FOR CHANGING THE FUNCTION AND STRUCTURE OF CHROMATIN GRINDING AND / OR DOMAINS |
US9512446B1 (en) | 2015-08-28 | 2016-12-06 | The General Hospital Corporation | Engineered CRISPR-Cas9 nucleases |
US9926546B2 (en) | 2015-08-28 | 2018-03-27 | The General Hospital Corporation | Engineered CRISPR-Cas9 nucleases |
CN108350449B (zh) | 2015-08-28 | 2022-05-31 | 通用医疗公司 | 工程化的CRISPR-Cas9核酸酶 |
IL241462A0 (en) | 2015-09-10 | 2015-11-30 | Yeda Res & Dev | Heterologous engineering of betalain pigments in plants |
CN108350453A (zh) | 2015-09-11 | 2018-07-31 | 通用医疗公司 | 核酸酶dsb的完全查询和测序(find-seq) |
AU2016326711B2 (en) | 2015-09-24 | 2022-11-03 | Editas Medicine, Inc. | Use of exonucleases to improve CRISPR/Cas-mediated genome editing |
WO2017053729A1 (en) | 2015-09-25 | 2017-03-30 | The Board Of Trustees Of The Leland Stanford Junior University | Nuclease-mediated genome editing of primary cells and enrichment thereof |
WO2017058791A1 (en) * | 2015-09-29 | 2017-04-06 | Agenovir Corporation | Compositions and methods for treatment of latent viral infections |
KR20180053748A (ko) | 2015-09-30 | 2018-05-23 | 더 제너럴 하스피탈 코포레이션 | 시퀀싱(circle-seq)에 의한 절단 반응의 포괄적인 시험관내 보고 |
WO2017059241A1 (en) | 2015-10-02 | 2017-04-06 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Lentiviral protein delivery system for rna-guided genome editing |
WO2017069958A2 (en) | 2015-10-09 | 2017-04-27 | The Brigham And Women's Hospital, Inc. | Modulation of novel immune checkpoint targets |
KR20180133374A (ko) | 2015-10-22 | 2018-12-14 | 더 브로드 인스티튜트, 인코퍼레이티드 | 타입 vi-b crispr 효소 및 시스템 |
CN108513575A (zh) | 2015-10-23 | 2018-09-07 | 哈佛大学的校长及成员们 | 核碱基编辑器及其用途 |
ES2699848T3 (es) | 2015-10-23 | 2019-02-13 | Caribou Biosciences Inc | Acido nucleico CRISPR clase 2 de tipo cruzado modificado que se dirige a ácidos nucleicos |
EP3368687B1 (en) | 2015-10-27 | 2021-09-29 | The Broad Institute, Inc. | Compositions and methods for targeting cancer-specific sequence variations |
WO2017075294A1 (en) | 2015-10-28 | 2017-05-04 | The Board Institute Inc. | Assays for massively combinatorial perturbation profiling and cellular circuit reconstruction |
WO2017075465A1 (en) | 2015-10-28 | 2017-05-04 | The Broad Institute Inc. | Compositions and methods for evaluating and modulating immune responses by detecting and targeting gata3 |
WO2017075451A1 (en) | 2015-10-28 | 2017-05-04 | The Broad Institute Inc. | Compositions and methods for evaluating and modulating immune responses by detecting and targeting pou2af1 |
WO2017075265A1 (en) | 2015-10-28 | 2017-05-04 | The Broad Institute, Inc. | Multiplex analysis of single cell constituents |
WO2017075478A2 (en) | 2015-10-28 | 2017-05-04 | The Broad Institute Inc. | Compositions and methods for evaluating and modulating immune responses by use of immune cell gene signatures |
EP4036228A1 (en) | 2015-11-13 | 2022-08-03 | Avellino Lab USA, Inc. | Methods for the treatment of corneal dystrophies |
EP3377086B1 (en) | 2015-11-19 | 2024-05-01 | The Brigham and Women's Hospital, Inc. | Lymphocyte antigen cd5-like (cd5l)-interleukin 12b (p40) heterodimers in immunity |
MA41013B1 (fr) | 2015-11-20 | 2018-07-31 | 4D Pharma Res Ltd | Compositions comprenant des souches bactériennes |
GB201520497D0 (en) | 2015-11-20 | 2016-01-06 | 4D Pharma Res Ltd | Compositions comprising bacterial strains |
AU2016359629B2 (en) * | 2015-11-23 | 2023-03-09 | Ranjan BATRA | Tracking and manipulating cellular RNA via nuclear delivery of CRISPR/Cas9 |
WO2017095946A1 (en) | 2015-11-30 | 2017-06-08 | Flagship Pioneering, Inc. | Methods and compositions relating to chondrisomes |
WO2017095960A1 (en) * | 2015-11-30 | 2017-06-08 | Synthetic Genomics, Inc. | Compositions and methods for expressing genes in algae |
WO2017093370A1 (en) * | 2015-12-03 | 2017-06-08 | Technische Universität München | T-cell specific genome editing |
US9771600B2 (en) | 2015-12-04 | 2017-09-26 | Caribou Biosciences, Inc. | Engineered nucleic acid-targeting nucleic acids |
US9988624B2 (en) | 2015-12-07 | 2018-06-05 | Zymergen Inc. | Microbial strain improvement by a HTP genomic engineering platform |
US11208649B2 (en) | 2015-12-07 | 2021-12-28 | Zymergen Inc. | HTP genomic engineering platform |
BR112018011503A2 (pt) | 2015-12-07 | 2018-12-04 | Zymergen Inc | promotores da corynebacterium glutamicum |
WO2017106657A1 (en) | 2015-12-18 | 2017-06-22 | The Broad Institute Inc. | Novel crispr enzymes and systems |
CN109072195A (zh) | 2015-12-30 | 2018-12-21 | 诺华股份有限公司 | 具有增强功效的免疫效应细胞疗法 |
US11672866B2 (en) | 2016-01-08 | 2023-06-13 | Paul N. DURFEE | Osteotropic nanoparticles for prevention or treatment of bone metastases |
US9856497B2 (en) | 2016-01-11 | 2018-01-02 | The Board Of Trustee Of The Leland Stanford Junior University | Chimeric proteins and methods of regulating gene expression |
KR20180095719A (ko) | 2016-01-11 | 2018-08-27 | 더 보드 어브 트러스티스 어브 더 리랜드 스탠포드 주니어 유니버시티 | 키메라 단백질 및 면역요법 방법 |
WO2017139309A1 (en) | 2016-02-12 | 2017-08-17 | Ceres, Inc. | Methods and materials for high throughput testing of mutagenized allele combinations |
US20190249172A1 (en) | 2016-02-18 | 2019-08-15 | The Regents Of The University Of California | Methods and compositions for gene editing in stem cells |
EP3420102B1 (en) | 2016-02-22 | 2024-04-03 | Massachusetts Institute of Technology | Methods for identifying and modulating immune phenotypes |
CN105543195A (zh) * | 2016-03-01 | 2016-05-04 | 中国水稻研究所 | 植物Cas9变体蛋白VQR及其编码基因与应用 |
CN105543196A (zh) * | 2016-03-01 | 2016-05-04 | 中国水稻研究所 | 植物Cas9变体蛋白VRER及其编码基因与应用 |
GB201612191D0 (en) | 2016-07-13 | 2016-08-24 | 4D Pharma Plc | Compositions comprising bacterial strains |
PT3313423T (pt) | 2016-03-04 | 2019-07-10 | 4D Pharma Plc | Composições que compreendem a estirpe blautia bacteriana para tratar a hipersensibilidade visceral |
JP2019515654A (ja) | 2016-03-16 | 2019-06-13 | ザ ジェイ. デヴィッド グラッドストーン インスティテューツ | 肥満及び/又は糖尿病を処置するための方法及び組成物、並びに候補処置薬剤を識別するための方法及び組成物 |
US11427861B2 (en) | 2016-03-17 | 2022-08-30 | Massachusetts Institute Of Technology | Methods for identifying and modulating co-occurant cellular phenotypes |
EP3219799A1 (en) | 2016-03-17 | 2017-09-20 | IMBA-Institut für Molekulare Biotechnologie GmbH | Conditional crispr sgrna expression |
US20200291370A1 (en) * | 2016-03-18 | 2020-09-17 | President And Fellows Of Harvard College | Mutant Cas Proteins |
WO2017165859A1 (en) * | 2016-03-24 | 2017-09-28 | Research Institute At Nationwide Children's Hospital | Modified viral capsid proteins |
US11512311B2 (en) | 2016-03-25 | 2022-11-29 | Editas Medicine, Inc. | Systems and methods for treating alpha 1-antitrypsin (A1AT) deficiency |
EP3433363A1 (en) | 2016-03-25 | 2019-01-30 | Editas Medicine, Inc. | Genome editing systems comprising repair-modulating enzyme molecules and methods of their use |
US11236313B2 (en) | 2016-04-13 | 2022-02-01 | Editas Medicine, Inc. | Cas9 fusion molecules, gene editing systems, and methods of use thereof |
KR20180134385A (ko) | 2016-04-15 | 2018-12-18 | 노파르티스 아게 | 선택적 단백질 발현을 위한 조성물 및 방법 |
AU2017257274B2 (en) | 2016-04-19 | 2023-07-13 | Massachusetts Institute Of Technology | Novel CRISPR enzymes and systems |
US11286478B2 (en) | 2016-04-19 | 2022-03-29 | The Broad Institute, Inc. | Cpf1 complexes with reduced indel activity |
KR102670601B1 (ko) | 2016-04-19 | 2024-05-29 | 더 브로드 인스티튜트, 인코퍼레이티드 | 신규한 crispr 효소 및 시스템 |
CN107304435A (zh) * | 2016-04-22 | 2017-10-31 | 中国科学院青岛生物能源与过程研究所 | 一种Cas9/RNA系统及其应用 |
ES2865481T3 (es) | 2016-04-29 | 2021-10-15 | Poseida Therapeutics Inc | Micelas basadas en poli(histidina) para la complejación y el aporte de proteínas y ácidos nucleicos |
US10767175B2 (en) | 2016-06-08 | 2020-09-08 | Agilent Technologies, Inc. | High specificity genome editing using chemically modified guide RNAs |
JP7267013B2 (ja) | 2016-06-17 | 2023-05-01 | ザ・ブロード・インスティテュート・インコーポレイテッド | Vi型crisprオルソログ及び系 |
AU2017280353B2 (en) | 2016-06-24 | 2021-11-11 | Inscripta, Inc. | Methods for generating barcoded combinatorial libraries |
MX2019000088A (es) | 2016-06-27 | 2019-08-29 | Broad Inst Inc | Composiciones y metodos para detectar y tratar la diabetes. |
WO2018005655A2 (en) | 2016-06-30 | 2018-01-04 | Zymergen Inc. | Methods for generating a bacterial hemoglobin library and uses thereof |
JP2019519241A (ja) | 2016-06-30 | 2019-07-11 | ザイマージェン インコーポレイテッド | グルコース透過酵素ライブラリーを生成するための方法およびその使用 |
CA3030783A1 (en) | 2016-07-13 | 2018-01-18 | Vertex Pharmaceuticals Incorporated | Methods, compositions and kits for increasing genome editing efficiency |
TWI802545B (zh) | 2016-07-13 | 2023-05-21 | 英商4D製藥有限公司 | 包含細菌菌株之組合物 |
JP7219376B2 (ja) | 2016-07-15 | 2023-02-08 | ノバルティス アーゲー | キメラ抗原受容体をキナーゼ阻害薬と併用して使用したサイトカイン放出症候群の治療及び予防 |
BR112019001887A2 (pt) | 2016-08-02 | 2019-07-09 | Editas Medicine Inc | composições e métodos para o tratamento de doença associada a cep290 |
WO2018027078A1 (en) | 2016-08-03 | 2018-02-08 | President And Fellows Of Harard College | Adenosine nucleobase editors and uses thereof |
US11078481B1 (en) | 2016-08-03 | 2021-08-03 | KSQ Therapeutics, Inc. | Methods for screening for cancer targets |
CA3033327A1 (en) | 2016-08-09 | 2018-02-15 | President And Fellows Of Harvard College | Programmable cas9-recombinase fusion proteins and uses thereof |
CA3033736C (en) * | 2016-08-12 | 2023-10-24 | Toolgen Incorporated | Manipulated immunoregulatory element and immunity altered thereby |
CN110114461A (zh) | 2016-08-17 | 2019-08-09 | 博德研究所 | 新型crispr酶和系统 |
US20210166783A1 (en) | 2016-08-17 | 2021-06-03 | The Broad Institute, Inc. | Methods for identifying class 2 crispr-cas systems |
WO2018035387A1 (en) | 2016-08-17 | 2018-02-22 | The Broad Institute, Inc. | Novel crispr enzymes and systems |
WO2018035364A1 (en) | 2016-08-17 | 2018-02-22 | The Broad Institute Inc. | Product and methods useful for modulating and evaluating immune responses |
WO2018034554A1 (ko) * | 2016-08-19 | 2018-02-22 | 주식회사 툴젠 | 인위적으로 조작된 신생혈관형성 조절 시스템 |
WO2018039145A1 (en) | 2016-08-20 | 2018-03-01 | Avellino Lab Usa, Inc. | Single guide rna, crispr/cas9 systems, and methods of use thereof |
WO2020225754A1 (en) | 2019-05-06 | 2020-11-12 | Mcmullen Tara | Crispr gene editing for autosomal dominant diseases |
WO2018039438A1 (en) | 2016-08-24 | 2018-03-01 | President And Fellows Of Harvard College | Incorporation of unnatural amino acids into proteins using base editing |
US11078483B1 (en) | 2016-09-02 | 2021-08-03 | KSQ Therapeutics, Inc. | Methods for measuring and improving CRISPR reagent function |
US20190262399A1 (en) | 2016-09-07 | 2019-08-29 | The Broad Institute, Inc. | Compositions and methods for evaluating and modulating immune responses |
WO2018049168A1 (en) | 2016-09-09 | 2018-03-15 | The Board Of Trustees Of The Leland Stanford Junior University | High-throughput precision genome editing |
IL247752A0 (en) | 2016-09-11 | 2016-11-30 | Yeda Res & Dev | Compositions and methods for modulating gene expression for site-directed mutagenesis |
US20190225974A1 (en) | 2016-09-23 | 2019-07-25 | BASF Agricultural Solutions Seed US LLC | Targeted genome optimization in plants |
CN109844126A (zh) | 2016-09-28 | 2019-06-04 | 诺华股份有限公司 | 基于多孔膜的大分子递送系统 |
AU2017335890B2 (en) | 2016-09-30 | 2024-05-09 | The Regents Of The University Of California | RNA-guided nucleic acid modifying enzymes and methods of use thereof |
US10669539B2 (en) | 2016-10-06 | 2020-06-02 | Pioneer Biolabs, Llc | Methods and compositions for generating CRISPR guide RNA libraries |
WO2018067991A1 (en) | 2016-10-07 | 2018-04-12 | The Brigham And Women's Hospital, Inc. | Modulation of novel immune checkpoint targets |
KR20240007715A (ko) * | 2016-10-14 | 2024-01-16 | 프레지던트 앤드 펠로우즈 오브 하바드 칼리지 | 핵염기 에디터의 aav 전달 |
GB201617559D0 (en) | 2016-10-17 | 2016-11-30 | University Court Of The University Of Edinburgh The | Swine comprising modified cd163 and associated methods |
EP3529359B1 (en) | 2016-10-18 | 2023-12-13 | Regents of the University of Minnesota | Tumor infiltrating lymphocytes for use in therapy |
EP3532614A1 (en) * | 2016-10-28 | 2019-09-04 | Genethon | Compositions and methods for the treatment of myotonic dystrophy |
WO2018081531A2 (en) | 2016-10-28 | 2018-05-03 | Ariad Pharmaceuticals, Inc. | Methods for human t-cell activation |
US20180245065A1 (en) | 2016-11-01 | 2018-08-30 | Novartis Ag | Methods and compositions for enhancing gene editing |
WO2018085693A1 (en) | 2016-11-04 | 2018-05-11 | Inari Agriculture, Inc. | Novel plant cells, plants, and seeds |
US9816093B1 (en) | 2016-12-06 | 2017-11-14 | Caribou Biosciences, Inc. | Engineered nucleic acid-targeting nucleic acids |
US11674128B2 (en) * | 2016-12-12 | 2023-06-13 | Tsinghua University | Engineering of a minimal SaCas9 CRISPR/Cas system for gene editing and transcriptional regulation optimized by enhanced guide RNA |
GB201621123D0 (en) | 2016-12-12 | 2017-01-25 | 4D Pharma Plc | Compositions comprising bacterial strains |
AU2017378427A1 (en) | 2016-12-14 | 2019-06-20 | Ligandal, Inc. | Methods and compositions for nucleic acid and protein payload delivery |
US10745677B2 (en) | 2016-12-23 | 2020-08-18 | President And Fellows Of Harvard College | Editing of CCR5 receptor gene to protect against HIV infection |
US11859219B1 (en) | 2016-12-30 | 2024-01-02 | Flagship Pioneering Innovations V, Inc. | Methods of altering a target nucleotide sequence with an RNA-guided nuclease and a single guide RNA |
WO2018127585A1 (en) | 2017-01-06 | 2018-07-12 | Txcell | Monospecific regulatory t cell population with cytotoxicity for b cells |
EP3346001A1 (en) | 2017-01-06 | 2018-07-11 | TXCell | Monospecific regulatory t cell population with cytotoxicity for b cells |
ES2949801T3 (es) | 2017-01-09 | 2023-10-03 | Whitehead Inst Biomedical Res | Métodos para alterar la expresión génica mediante la perturbación de multímeros de factores de transcripción que estructuran bucles reguladores |
EP4043485A1 (en) | 2017-01-26 | 2022-08-17 | Novartis AG | Cd28 compositions and methods for chimeric antigen receptor therapy |
WO2018140899A1 (en) | 2017-01-28 | 2018-08-02 | Inari Agriculture, Inc. | Novel plant cells, plants, and seeds |
JP2020506700A (ja) | 2017-01-31 | 2020-03-05 | ノバルティス アーゲー | 多重特異性を有するキメラt細胞受容体タンパク質を用いた癌の治療 |
TW201839136A (zh) | 2017-02-06 | 2018-11-01 | 瑞士商諾華公司 | 治療血色素異常症之組合物及方法 |
KR20190116282A (ko) | 2017-02-10 | 2019-10-14 | 지머젠 인코포레이티드 | 복수의 숙주를 위한 다중 dna 구조체의 조립 및 편집을 위한 모듈식 범용 플라스미드 디자인 전략 |
WO2018160731A1 (en) | 2017-02-28 | 2018-09-07 | Novartis Ag | Shp inhibitor compositions and uses for chimeric antigen receptor therapy |
WO2018160865A1 (en) | 2017-03-01 | 2018-09-07 | Charles Jeffrey Brinker | Active targeting of cells by monosized protocells |
GB2574769A (en) * | 2017-03-03 | 2019-12-18 | Univ California | RNA Targeting of mutations via suppressor tRNAs and deaminases |
EP3592853A1 (en) | 2017-03-09 | 2020-01-15 | President and Fellows of Harvard College | Suppression of pain by gene editing |
JP2020510439A (ja) | 2017-03-10 | 2020-04-09 | プレジデント アンド フェローズ オブ ハーバード カレッジ | シトシンからグアニンへの塩基編集因子 |
WO2018170184A1 (en) | 2017-03-14 | 2018-09-20 | Editas Medicine, Inc. | Systems and methods for the treatment of hemoglobinopathies |
CA3056236A1 (en) | 2017-03-15 | 2018-09-20 | The Broad Institute, Inc. | Novel cas13b orthologues crispr enzymes and systems |
US20200115753A1 (en) | 2017-03-17 | 2020-04-16 | Massachusetts Institute Of Technology | Methods for identifying and modulating co-occurant cellular phenotypes |
SG11201908658TA (en) | 2017-03-23 | 2019-10-30 | Harvard College | Nucleobase editors comprising nucleic acid programmable dna binding proteins |
WO2018183908A1 (en) | 2017-03-31 | 2018-10-04 | Dana-Farber Cancer Institute, Inc. | Compositions and methods for treating ovarian tumors |
US11913075B2 (en) | 2017-04-01 | 2024-02-27 | The Broad Institute, Inc. | Methods and compositions for detecting and modulating an immunotherapy resistance gene signature in cancer |
EP3610266A4 (en) | 2017-04-12 | 2021-04-21 | Massachusetts Eye and Ear Infirmary | TUMOR SIGNATURE OF METASTASIS, COMPOSITIONS OF SUBSTANCES AND USES THEREOF |
WO2018191388A1 (en) | 2017-04-12 | 2018-10-18 | The Broad Institute, Inc. | Novel type vi crispr orthologs and systems |
US20210115407A1 (en) | 2017-04-12 | 2021-04-22 | The Broad Institute, Inc. | Respiratory and sweat gland ionocytes |
WO2018191750A2 (en) | 2017-04-14 | 2018-10-18 | The Broad Institute Inc. | Novel delivery of large payloads |
WO2018195019A1 (en) | 2017-04-18 | 2018-10-25 | The Broad Institute Inc. | Compositions for detecting secretion and methods of use |
WO2018195545A2 (en) | 2017-04-21 | 2018-10-25 | The General Hospital Corporation | Variants of cpf1 (cas12a) with altered pam specificity |
WO2018195486A1 (en) | 2017-04-21 | 2018-10-25 | The Broad Institute, Inc. | Targeted delivery to beta cells |
WO2018201086A1 (en) | 2017-04-28 | 2018-11-01 | Editas Medicine, Inc. | Methods and systems for analyzing guide rna molecules |
EP3615068A1 (en) | 2017-04-28 | 2020-03-04 | Novartis AG | Bcma-targeting agent, and combination therapy with a gamma secretase inhibitor |
US20200055948A1 (en) | 2017-04-28 | 2020-02-20 | Novartis Ag | Cells expressing a bcma-targeting chimeric antigen receptor, and combination therapy with a gamma secretase inhibitor |
US11591601B2 (en) | 2017-05-05 | 2023-02-28 | The Broad Institute, Inc. | Methods for identification and modification of lncRNA associated with target genotypes and phenotypes |
WO2019103857A1 (en) | 2017-11-22 | 2019-05-31 | Iovance Biotherapeutics, Inc. | Expansion of peripheral blood lymphocytes (pbls) from peripheral blood |
CN110869498A (zh) | 2017-05-10 | 2020-03-06 | 加利福尼亚大学董事会 | 经由核递送crispr/cas9导向编辑细胞rna |
EP3622070A2 (en) | 2017-05-10 | 2020-03-18 | Editas Medicine, Inc. | Crispr/rna-guided nuclease systems and methods |
US11560566B2 (en) | 2017-05-12 | 2023-01-24 | President And Fellows Of Harvard College | Aptazyme-embedded guide RNAs for use with CRISPR-Cas9 in genome editing and transcriptional activation |
US11692184B2 (en) | 2017-05-16 | 2023-07-04 | The Regents Of The University Of California | Thermostable RNA-guided endonucleases and methods of use thereof |
CA3063739A1 (en) | 2017-05-18 | 2018-11-22 | The Broad Institute, Inc. | Systems, methods, and compositions for targeted nucleic acid editing |
PT3630136T (pt) | 2017-05-22 | 2021-06-11 | 4D Pharma Res Ltd | Composições que compreendem estirpes bacterianas |
MA41708A (fr) | 2017-05-24 | 2020-04-08 | 4D Pharma Res Ltd | Compositions comprenant des souches bactériennes |
CN110997728A (zh) | 2017-05-25 | 2020-04-10 | 通用医疗公司 | 二分型碱基编辑器(bbe)结构和ii-型-cas9锌指编辑 |
EP3630975A4 (en) | 2017-05-26 | 2021-03-10 | North Carolina State University | CHANGED GUIDE RNAS FOR MODULATING CAS9 ACTIVITY AND USAGE PROCEDURES |
EP3409104A1 (en) | 2017-05-31 | 2018-12-05 | Vilmorin et Cie | Tomato plant resistant to tomato yellow leaf curl virus, powdery mildew, and nematodes |
EP3409106A1 (en) | 2017-06-01 | 2018-12-05 | Vilmorin et Cie | Tolerance in plants of solanum lycopersicum to the tobamovirus tomato brown rugose fruit virus (tbrfv) |
WO2020249996A1 (en) | 2019-06-14 | 2020-12-17 | Vilmorin & Cie | Resistance in plants of solanum lycopersicum to the tobamovirus tomato brown rugose fruit virus |
WO2018226762A1 (en) | 2017-06-05 | 2018-12-13 | Fred Hutchinson Cancer Research Center | Genomic safe harbors for genetic therapies in human stem cells and engineered nanoparticles to provide targeted genetic therapies |
US20200370058A1 (en) | 2017-06-06 | 2020-11-26 | Zymergen Inc. | A htp genomic engineering platform for improving escherichia coli |
EP3635112A2 (en) | 2017-06-06 | 2020-04-15 | Zymergen, Inc. | A htp genomic engineering platform for improving fungal strains |
WO2018227025A1 (en) * | 2017-06-07 | 2018-12-13 | Arc Bio, Llc | Creation and use of guide nucleic acids |
WO2018227114A1 (en) | 2017-06-09 | 2018-12-13 | Editas Medicine, Inc. | Engineered cas9 nucleases |
JP2020524993A (ja) | 2017-06-13 | 2020-08-27 | フラッグシップ パイオニアリング イノベーションズ ブイ, インコーポレイテッド | クロンを含む組成物及びその使用 |
MD3638271T2 (ro) | 2017-06-14 | 2021-03-31 | 4D Pharma Res Ltd | Compoziții cuprizând tulpini bacteriene |
HRP20220747T1 (hr) | 2017-06-14 | 2022-10-14 | 4D Pharma Research Limited | Pripravci koji sadrže bakterijske sojeve |
KR102634727B1 (ko) | 2017-06-14 | 2024-02-07 | 위스콘신 얼럼나이 리서어치 화운데이션 | 변형된 가이드 rna, crispr-리보뉴클레오프로테인 복합체 및 사용 방법 |
WO2018232195A1 (en) | 2017-06-14 | 2018-12-20 | The Broad Institute, Inc. | Compositions and methods targeting complement component 3 for inhibiting tumor growth |
US9982279B1 (en) | 2017-06-23 | 2018-05-29 | Inscripta, Inc. | Nucleic acid-guided nucleases |
US10011849B1 (en) | 2017-06-23 | 2018-07-03 | Inscripta, Inc. | Nucleic acid-guided nucleases |
WO2019005884A1 (en) | 2017-06-26 | 2019-01-03 | The Broad Institute, Inc. | CRISPR / CAS-ADENINE DEAMINASE COMPOSITIONS, SYSTEMS AND METHODS FOR TARGETED NUCLEIC ACID EDITION |
JP2020530307A (ja) | 2017-06-30 | 2020-10-22 | インティマ・バイオサイエンス,インコーポレーテッド | 遺伝子治療のためのアデノ随伴ウイルスベクター |
US20200140896A1 (en) | 2017-06-30 | 2020-05-07 | Novartis Ag | Methods for the treatment of disease with gene editing systems |
EP3652312A1 (en) | 2017-07-14 | 2020-05-20 | Editas Medicine, Inc. | Systems and methods for targeted integration and genome editing and detection thereof using integrated priming sites |
WO2019018551A2 (en) | 2017-07-18 | 2019-01-24 | Lee Tzumin | METHODS AND COMPOSITIONS FOR GENETICALLY GENETIC HANDLING OF GENES AND CELLS |
WO2019023291A2 (en) | 2017-07-25 | 2019-01-31 | Dana-Farber Cancer Institute, Inc. | COMPOSITIONS AND METHODS FOR PRODUCTION AND DECODING OF GUIDE RNA LIBRARIES AND USES THEREOF |
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) |
MX2020001340A (es) | 2017-07-31 | 2020-08-31 | Reflection Biotechnologies Ltd | Modelos celulares y terapias para enfermedades oculares. |
WO2019040650A1 (en) | 2017-08-23 | 2019-02-28 | The General Hospital Corporation | GENETICALLY MODIFIED CRISPR-CAS9 NUCLEASES HAVING MODIFIED PAM SPECIFICITY |
US11319532B2 (en) | 2017-08-30 | 2022-05-03 | President And Fellows Of Harvard College | High efficiency base editors comprising Gam |
US11713452B2 (en) | 2017-09-08 | 2023-08-01 | University Of North Texas Health Science Center | Engineered CAS9 variants |
JP7317023B2 (ja) | 2017-09-20 | 2023-07-28 | ザ・ユニバーシティ・オブ・ブリティッシュ・コロンビア | 新規抗hla-a2抗体、およびその使用 |
IT201700105372A1 (it) * | 2017-09-20 | 2019-03-20 | Fondazione St Italiano Tecnologia | Molecola di acido nucleico funzionale e relativo uso |
WO2019060759A1 (en) | 2017-09-21 | 2019-03-28 | Dana-Farber Cancer Institute, Inc. | ISOLATION, PRESERVATION, COMPOSITIONS AND USES OF PLANT EXTRACTS JUSTICIA |
AU2018338318B2 (en) | 2017-09-21 | 2022-12-22 | Massachusetts Institute Of Technology | Systems, methods, and compositions for targeted nucleic acid editing |
US10933027B1 (en) | 2017-09-25 | 2021-03-02 | National Technology & Engineering Solutions Of Sandia, Llc | Expanded pore particles and delivery methods thereof |
US20200255828A1 (en) | 2017-10-04 | 2020-08-13 | The Broad Institute, Inc. | Methods and compositions for altering function and structure of chromatin loops and/or domains |
EP3694993A4 (en) | 2017-10-11 | 2021-10-13 | The General Hospital Corporation | METHOD OF DETECTING A SITE-SPECIFIC AND UNDESIRED GENOMIC DESAMINATION INDUCED BY BASE EDITING TECHNOLOGIES |
US11680296B2 (en) | 2017-10-16 | 2023-06-20 | Massachusetts Institute Of Technology | Mycobacterium tuberculosis host-pathogen interaction |
CN111757937A (zh) | 2017-10-16 | 2020-10-09 | 布罗德研究所股份有限公司 | 腺苷碱基编辑器的用途 |
KR20200085781A (ko) | 2017-10-20 | 2020-07-15 | 프레드 헛친슨 켄서 리서치 센터 | 선택된 항체를 발현하도록 유전자 변형된 b 세포를 생산하기 위한 시스템 및 방법 |
US11547614B2 (en) | 2017-10-31 | 2023-01-10 | The Broad Institute, Inc. | Methods and compositions for studying cell evolution |
WO2019089798A1 (en) | 2017-10-31 | 2019-05-09 | Novartis Ag | Anti-car compositions and methods |
US20210180053A1 (en) | 2017-11-01 | 2021-06-17 | Novartis Ag | Synthetic rnas and methods of use |
EP3710039A4 (en) | 2017-11-13 | 2021-08-04 | The Broad Institute, Inc. | METHODS AND COMPOSITIONS FOR CANCER TREATMENT BY TARGETING THE CLEC2D-KLRB1 PATH |
WO2019099943A1 (en) | 2017-11-16 | 2019-05-23 | Astrazeneca Ab | Compositions and methods for improving the efficacy of cas9-based knock-in strategies |
SG11202004457XA (en) | 2017-11-17 | 2020-06-29 | Iovance Biotherapeutics Inc | Til expansion from fine needle aspirates and small biopsies |
WO2019113506A1 (en) | 2017-12-07 | 2019-06-13 | The Broad Institute, Inc. | Methods and compositions for multiplexing single cell and single nuclei sequencing |
CN109912702B (zh) * | 2017-12-13 | 2021-03-16 | 中国科学院遗传与发育生物学研究所 | 蛋白质OsARE1在调控植物抗低氮性中的应用 |
US11578323B2 (en) | 2017-12-14 | 2023-02-14 | Bayer Healthcare Llc | RNA-programmable endonuclease systems and their use in genome editing and other applications |
US20190201548A1 (en) | 2017-12-29 | 2019-07-04 | Rubius Therapeutics, Inc. | Gene editing and targeted transcriptional modulation for engineering erythroid cells |
US11994512B2 (en) | 2018-01-04 | 2024-05-28 | Massachusetts Institute Of Technology | Single-cell genomic methods to generate ex vivo cell systems that recapitulate in vivo biology with improved fidelity |
AU2019207409B2 (en) | 2018-01-12 | 2023-02-23 | Basf Se | Gene underlying the number of spikelets per spike qtl in wheat on chromosome 7a |
IL276080B2 (en) | 2018-01-17 | 2023-10-01 | Vertex Pharma | DNA-PK suppressor compounds, UTP-containing preparations and their uses |
CA3088791A1 (en) | 2018-01-17 | 2019-07-25 | Vertex Pharmaceuticals Incorporated | Quinoxalinone compounds, compositions, methods, and kits for increasing genome editing efficiency |
IL276082B2 (en) | 2018-01-17 | 2024-01-01 | Vertex Pharma | DNA-PK inhibitor compounds, preparations containing them and their uses |
US20190233816A1 (en) | 2018-01-26 | 2019-08-01 | Massachusetts Institute Of Technology | Structure-guided chemical modification of guide rna and its applications |
US11926835B1 (en) | 2018-01-29 | 2024-03-12 | Inari Agriculture Technology, Inc. | Methods for efficient tomato genome editing |
EP3749764A1 (en) | 2018-02-08 | 2020-12-16 | Zymergen, Inc. | Genome editing using crispr in corynebacterium |
US20210054353A1 (en) | 2018-03-19 | 2021-02-25 | Crispr Therapeutics Ag | Novel rna-programmable endonuclease systems and uses thereof |
CA3096274A1 (en) | 2018-04-06 | 2019-10-10 | Children's Medical Center Corporation | Compositions and methods for somatic cell reprogramming and modulating imprinting |
WO2019197678A1 (en) | 2018-04-13 | 2019-10-17 | Sangamo Therapeutics France | Chimeric antigen receptor specific for interleukin-23 receptor |
JP7460539B2 (ja) | 2018-04-17 | 2024-04-02 | ザ ジェネラル ホスピタル コーポレイション | 核酸を結合、修飾、および切断する物質の基質選択性および部位のためのin vitroでの高感度アッセイ |
BR112020021229A2 (pt) | 2018-04-19 | 2021-02-02 | The Regents Of The University Of California | composições e métodos para edição de genes |
US20210071240A1 (en) | 2018-04-19 | 2021-03-11 | Massachusetts Institute Of Technology | Single-stranded break detection in double-stranded dna |
HUE059223T2 (hu) | 2018-04-24 | 2022-10-28 | Kws Saat Se & Co Kgaa | Jobb emészthetõségû növények és marker haplotípusok |
US11957695B2 (en) | 2018-04-26 | 2024-04-16 | The Broad Institute, Inc. | Methods and compositions targeting glucocorticoid signaling for modulating immune responses |
US20210238347A1 (en) | 2018-04-27 | 2021-08-05 | Genedit Inc. | Cationic polymer and use for biomolecule delivery |
US20210047405A1 (en) | 2018-04-27 | 2021-02-18 | Novartis Ag | Car t cell therapies with enhanced efficacy |
WO2019210268A2 (en) | 2018-04-27 | 2019-10-31 | The Broad Institute, Inc. | Sequencing-based proteomics |
CN112368003A (zh) | 2018-04-27 | 2021-02-12 | 艾欧凡斯生物治疗公司 | 肿瘤浸润淋巴细胞的基因编辑及其在免疫治疗中的用途 |
WO2019213660A2 (en) | 2018-05-04 | 2019-11-07 | The Broad Institute, Inc. | Compositions and methods for modulating cgrp signaling to regulate innate lymphoid cell inflammatory responses |
MX2020011757A (es) | 2018-05-10 | 2021-01-08 | Auxolytic Ltd | Metodos y composiciones de terapia genica que utilizan celulas regulables auxotroficas. |
EP3794130A4 (en) | 2018-05-16 | 2022-07-27 | Synthego Corporation | METHODS AND SYSTEMS FOR DESIGN AND USE OF GUIDE RNA |
US20210371932A1 (en) | 2018-06-01 | 2021-12-02 | Massachusetts Institute Of Technology | Methods and compositions for detecting and modulating microenvironment gene signatures from the csf of metastasis patients |
US11866719B1 (en) | 2018-06-04 | 2024-01-09 | Inari Agriculture Technology, Inc. | Heterologous integration of regulatory elements to alter gene expression in wheat cells and wheat plants |
EP3806888B1 (en) | 2018-06-12 | 2024-01-31 | Obsidian Therapeutics, Inc. | Pde5 derived regulatory constructs and methods of use in immunotherapy |
AU2019284911A1 (en) | 2018-06-13 | 2020-12-17 | Novartis Ag | BCMA chimeric antigen receptors and uses thereof |
US10227576B1 (en) | 2018-06-13 | 2019-03-12 | Caribou Biosciences, Inc. | Engineered cascade components and cascade complexes |
US11045554B1 (en) | 2018-06-22 | 2021-06-29 | National Technology & Engineering Solutions Of Sandia, Llc | Lipid-coated particles for treating viral infections |
KR20210040943A (ko) | 2018-06-26 | 2021-04-14 | 매사추세츠 인스티튜트 오브 테크놀로지 | Crispr 이펙터 시스템 기반 증폭 방법, 시스템, 및 진단 |
KR20210024009A (ko) | 2018-06-26 | 2021-03-04 | 더 브로드 인스티튜트, 인코퍼레이티드 | Crispr/cas 및 트랜스포사제 기반 증폭 조성물, 시스템 및 방법 |
WO2020002592A1 (en) | 2018-06-29 | 2020-01-02 | Stichting Het Nederlands Kanker Instituut - Antoni Van Leeuwenhoek Ziekenhuis | Traf2 inhibitors for use in the treatment of a cancer |
JP2021530212A (ja) | 2018-07-13 | 2021-11-11 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニアThe Regents Of The University Of California | レトロトランスポゾンベースの送達媒体及びその使用方法 |
SG11202102068TA (en) | 2018-07-31 | 2021-03-30 | Broad Inst Inc | Novel crispr enzymes and systems |
WO2020033601A1 (en) | 2018-08-07 | 2020-02-13 | The Broad Institute, Inc. | Novel cas12b enzymes and systems |
EP3607819A1 (en) | 2018-08-10 | 2020-02-12 | Vilmorin et Cie | Resistance to xanthomonas campestris pv. campestris (xcc) in cauliflower |
AU2019318135A1 (en) | 2018-08-10 | 2021-03-04 | Sangamo Therapeutics France | New car constructs comprising TNFR2 domains |
CN112703250A (zh) | 2018-08-15 | 2021-04-23 | 齐默尔根公司 | CRISPRi在高通量代谢工程中的应用 |
WO2020041387A1 (en) | 2018-08-20 | 2020-02-27 | The Brigham And Women's Hospital, Inc. | Degradation domain modifications for spatio-temporal control of rna-guided nucleases |
US20210317429A1 (en) | 2018-08-20 | 2021-10-14 | The Broad Institute, Inc. | Methods and compositions for optochemical control of crispr-cas9 |
SG11202101801RA (en) | 2018-08-23 | 2021-03-30 | Sangamo Therapeutics Inc | Engineered target specific base editors |
US11459551B1 (en) | 2018-08-31 | 2022-10-04 | Inari Agriculture Technology, Inc. | Compositions, systems, and methods for genome editing |
WO2020051507A1 (en) | 2018-09-06 | 2020-03-12 | The Broad Institute, Inc. | Nucleic acid assemblies for use in targeted delivery |
US20210198642A1 (en) | 2018-09-07 | 2021-07-01 | Astrazeneca Ab | Compositions and methods for improved nucleases |
EP3849565A4 (en) | 2018-09-12 | 2022-12-28 | Fred Hutchinson Cancer Research Center | REDUCING CD33 EXPRESSION FOR SELECTIVE PROTECTION OF THERAPEUTIC CELLS |
US20220088224A1 (en) | 2018-09-18 | 2022-03-24 | Vnv Newco Inc. | Arc-based capsids and uses thereof |
CA3113676A1 (en) | 2018-09-21 | 2020-03-26 | President And Fellows Of Harvard College | Methods and compositions for treating diabetes, and methods for enriching mrna coding for secreted proteins |
WO2020077236A1 (en) | 2018-10-12 | 2020-04-16 | The Broad Institute, Inc. | Method for extracting nuclei or whole cells from formalin-fixed paraffin-embedded tissues |
US20210379057A1 (en) | 2018-10-16 | 2021-12-09 | Massachusetts Institute Of Technology | Nutlin-3a for use in treating a mycobacterium tuberculosis infection |
US20210395709A1 (en) * | 2018-10-18 | 2021-12-23 | Chan Zuckerberg Biohub, Inc. | Methods and compositions involving thermostable cas9 protein variants |
EP3870600A1 (en) | 2018-10-24 | 2021-09-01 | Obsidian Therapeutics, Inc. | Er tunable protein regulation |
EP3870628B1 (en) | 2018-10-24 | 2024-04-03 | Genedit Inc. | Cationic polymer with alkyl side chains and use for biomolecule delivery |
US11407995B1 (en) | 2018-10-26 | 2022-08-09 | Inari Agriculture Technology, Inc. | RNA-guided nucleases and DNA binding proteins |
WO2020092704A1 (en) | 2018-10-31 | 2020-05-07 | Zymergen Inc. | Multiplexed deterministic assembly of dna libraries |
US11434477B1 (en) | 2018-11-02 | 2022-09-06 | Inari Agriculture Technology, Inc. | RNA-guided nucleases and DNA binding proteins |
AU2019374761A1 (en) | 2018-11-05 | 2021-06-10 | Iovance Biotherapeutics, Inc. | Processes for production of tumor infiltrating lymphocytes and uses of the same in immunotherapy |
US11739320B2 (en) | 2018-11-05 | 2023-08-29 | Wisconsin Alumni Research Foundation | Gene correction of Pompe disease and other autosomal recessive disorders via RNA-guided nucleases |
JP2022512899A (ja) | 2018-11-05 | 2022-02-07 | アイオバンス バイオセラピューティクス,インコーポレイテッド | 抗pd-1抗体に対して不応性のnsclc患者の治療 |
US20220033775A1 (en) | 2018-11-05 | 2022-02-03 | Iovance Biotherapeutics, Inc. | Expansion of tils utilizing akt pathways inhibitors |
TW202039829A (zh) | 2018-11-05 | 2020-11-01 | 美商艾歐凡斯生物治療公司 | 改善之腫瘤反應性t細胞的選擇 |
US11166996B2 (en) | 2018-12-12 | 2021-11-09 | Flagship Pioneering Innovations V, Inc. | Anellovirus compositions and methods of use |
EP3894550A4 (en) | 2018-12-14 | 2023-01-04 | Pioneer Hi-Bred International, Inc. | NEW CRISPR-CAS SYSTEMS FOR GENOME EDITING |
WO2020131586A2 (en) | 2018-12-17 | 2020-06-25 | The Broad Institute, Inc. | Methods for identifying neoantigens |
WO2020131862A1 (en) | 2018-12-17 | 2020-06-25 | The Broad Institute, Inc. | Crispr-associated transposase systems and methods of use thereof |
JP2022515124A (ja) | 2018-12-19 | 2022-02-17 | キングス カレッジ ロンドン | 免疫療法および組成物 |
US20220193131A1 (en) | 2018-12-19 | 2022-06-23 | Iovance Biotherapeutics, Inc. | Methods of Expanding Tumor Infiltrating Lymphocytes Using Engineered Cytokine Receptor Pairs and Uses Thereof |
EP4339286A2 (en) * | 2018-12-27 | 2024-03-20 | LifeEDIT Therapeutics, Inc. | Polypeptides useful for gene editing and methods of use |
WO2020141199A1 (en) | 2019-01-03 | 2020-07-09 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and pharmaceutical compositions for enhancing cd8+ t cell-dependent immune responses in subjects suffering from cancer |
US11739156B2 (en) | 2019-01-06 | 2023-08-29 | The Broad Institute, Inc. Massachusetts Institute of Technology | Methods and compositions for overcoming immunosuppression |
EP3921417A4 (en) | 2019-02-04 | 2022-11-09 | The General Hospital Corporation | ADENINE DNA BASE EDITOR VARIANTS WITH REDUCED OFF-TARGET RNA EDITING |
US20220145330A1 (en) | 2019-02-10 | 2022-05-12 | The J. David Gladstone Institutes, a testamentary trust established under the Will of J. David Glads | Modified mitochondrion and methods of use thereof |
US10913941B2 (en) | 2019-02-14 | 2021-02-09 | Metagenomi Ip Technologies, Llc | Enzymes with RuvC domains |
CA3241703A1 (en) * | 2019-02-14 | 2020-08-20 | Metagenomi, Inc. | Enzymes with ruvc domains |
US20220298494A1 (en) * | 2019-02-14 | 2022-09-22 | Metagenomi Ip Technologies, Llc | Enzymes with ruvc domains |
GB201902277D0 (en) | 2019-02-19 | 2019-04-03 | King S College London | Therapeutic agents |
MX2021010288A (es) | 2019-03-01 | 2021-09-23 | Iovance Biotherapeutics Inc | Expansion de linfocitos infiltrantes de tumores a partir de tumores liquidos y usos terapeuticos de los mismos. |
EP4219700A1 (en) | 2019-03-07 | 2023-08-02 | The Regents of the University of California | Crispr-cas effector polypeptides and methods of use thereof |
KR20210136997A (ko) | 2019-03-08 | 2021-11-17 | 지머젠 인코포레이티드 | 미생물에서 반복적 게놈 편집 |
US11053515B2 (en) | 2019-03-08 | 2021-07-06 | Zymergen Inc. | Pooled genome editing in microbes |
SG11202109172TA (en) | 2019-03-08 | 2021-09-29 | Obsidian Therapeutics Inc | Human carbonic anhydrase 2 compositions and methods for tunable regulation |
DE112020001342T5 (de) | 2019-03-19 | 2022-01-13 | President and Fellows of Harvard College | Verfahren und Zusammensetzungen zum Editing von Nukleotidsequenzen |
WO2020206036A1 (en) | 2019-04-01 | 2020-10-08 | The Broad Institute, Inc. | Novel nucleic acid modifier |
GB201905360D0 (en) | 2019-04-16 | 2019-05-29 | Univ Nottingham | Fungal strains, production and uses thereof |
EP3958849A1 (en) | 2019-04-23 | 2022-03-02 | Genedit Inc. | Cationic polymer with alkyl side chains |
EP3959320A1 (en) | 2019-04-24 | 2022-03-02 | Novartis AG | Compositions and methods for selective protein degradation |
EP3963062A4 (en) | 2019-05-03 | 2023-09-06 | Specific Biologics Inc. | LIPID ENCAPSULATED DOUBLE-CLEVISING ENDONUCLEASE FOR DNA AND GENE EDITING |
EP3969607A1 (en) | 2019-05-13 | 2022-03-23 | KWS SAAT SE & Co. KGaA | Drought tolerance in corn |
US20220249559A1 (en) | 2019-05-13 | 2022-08-11 | Iovance Biotherapeutics, Inc. | Methods and compositions for selecting tumor infiltrating lymphocytes and uses of the same in immunotherapy |
WO2020236967A1 (en) | 2019-05-20 | 2020-11-26 | The Broad Institute, Inc. | Random crispr-cas deletion mutant |
WO2020236972A2 (en) | 2019-05-20 | 2020-11-26 | The Broad Institute, Inc. | Non-class i multi-component nucleic acid targeting systems |
AR118995A1 (es) | 2019-05-25 | 2021-11-17 | Kws Saat Se & Co Kgaa | Mejorador de la inducción de haploides |
EP3976015A1 (en) | 2019-05-28 | 2022-04-06 | Genedit Inc. | Polymer comprising multiple functionalized sidechains for biomolecule delivery |
WO2020243661A1 (en) | 2019-05-31 | 2020-12-03 | The Broad Institute, Inc. | Methods for treating metabolic disorders by targeting adcy5 |
WO2020244759A1 (en) | 2019-06-05 | 2020-12-10 | Klemm & Sohn Gmbh & Co. Kg | New plants having a white foliage phenotype |
WO2020254850A1 (en) | 2019-06-21 | 2020-12-24 | Vilmorin & Cie | Improvement of quality and permanence of green color of peppers at maturity and over-maturity |
EP3990633A1 (en) | 2019-06-25 | 2022-05-04 | Inari Agriculture Technology, Inc. | Improved homology dependent repair genome editing |
BR112021026832A2 (pt) | 2019-07-02 | 2022-05-10 | Hutchinson Fred Cancer Res | Vetores ad35 recombinantes e aprimoramentos da terapia gênica relacionada |
WO2021009299A1 (en) | 2019-07-17 | 2021-01-21 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Bcl-xl:fkbp12 fusion proteins suitable for screening agents capable of slowing down the aging process |
WO2021019272A1 (en) | 2019-07-31 | 2021-02-04 | Vilmorin & Cie | Tolerance to tolcndv in cucumber |
EP4007595A4 (en) * | 2019-08-02 | 2023-09-27 | Monsanto Technology LLC | METHODS AND COMPOSITIONS FOR PROMOTING TARGETED GENOME CHANGES USING HUH ENDONUCLEASES |
EP3772542A1 (en) | 2019-08-07 | 2021-02-10 | KWS SAAT SE & Co. KGaA | Modifying genetic variation in crops by modulating the pachytene checkpoint protein 2 |
WO2021023307A1 (zh) * | 2019-08-08 | 2021-02-11 | 复旦大学 | CRISPR/Cas9基因编辑系统及其应用 |
WO2021028359A1 (en) | 2019-08-09 | 2021-02-18 | Sangamo Therapeutics France | Controlled expression of chimeric antigen receptors in t cells |
WO2021041922A1 (en) | 2019-08-30 | 2021-03-04 | The Broad Institute, Inc. | Crispr-associated mu transposase systems |
WO2021046451A1 (en) | 2019-09-06 | 2021-03-11 | Obsidian Therapeutics, Inc. | Compositions and methods for dhfr tunable protein regulation |
WO2021050512A1 (en) * | 2019-09-09 | 2021-03-18 | Beam Therapeutics Inc. | Novel crispr enzymes, methods, systems and uses thereof |
US20230025039A1 (en) | 2019-09-20 | 2023-01-26 | The Broad Institute, Inc. | Novel type vi crispr enzymes and systems |
JP2022548320A (ja) | 2019-09-23 | 2022-11-17 | オメガ セラピューティクス, インコーポレイテッド | アポリポタンパク質b(apob)遺伝子発現をモジュレートするための組成物および方法 |
US11987791B2 (en) | 2019-09-23 | 2024-05-21 | Omega Therapeutics, Inc. | Compositions and methods for modulating hepatocyte nuclear factor 4-alpha (HNF4α) gene expression |
US11981922B2 (en) | 2019-10-03 | 2024-05-14 | Dana-Farber Cancer Institute, Inc. | Methods and compositions for the modulation of cell interactions and signaling in the tumor microenvironment |
EP3808766A1 (en) | 2019-10-15 | 2021-04-21 | Sangamo Therapeutics France | Chimeric antigen receptor specific for interleukin-23 receptor |
CN114846022A (zh) | 2019-10-17 | 2022-08-02 | 科沃施种子欧洲股份两合公司 | 通过阻抑基因的下调增强作物的疾病抗性 |
US20220389381A1 (en) | 2019-10-25 | 2022-12-08 | Iovance Biotherapeutics, Inc. | Gene editing of tumor infiltrating lymphocytes and uses of same in immunotherapy |
TW202132333A (zh) * | 2019-11-13 | 2021-09-01 | 瑞士商Crispr治療公司 | 製造可表達嵌合抗原受體的t細胞製法 |
WO2021095012A1 (en) * | 2019-11-13 | 2021-05-20 | Crispr Therapeutics Ag | Methods of manufacturing car-t cells |
WO2021094805A1 (en) | 2019-11-14 | 2021-05-20 | Vilmorin & Cie | Resistance to acidovorax valerianellae in corn salad |
US20240016735A1 (en) | 2019-11-22 | 2024-01-18 | President And Fellows Of Harvard College | Ionic liquids for drug delivery |
JP2023504314A (ja) | 2019-12-02 | 2023-02-02 | シェイプ セラピューティクス インコーポレイテッド | 治療的編集 |
CA3161104A1 (en) | 2019-12-11 | 2021-06-17 | Cecile Chartier-Courtaud | Processes for the production of tumor infiltrating lymphocytes (tils) and methods of using the same |
IL271656A (en) | 2019-12-22 | 2021-06-30 | Yeda Res & Dev | System and methods for identifying cells that have undergone genome editing |
AU2021207810A1 (en) | 2020-01-13 | 2022-08-04 | Sana Biotechnology, Inc. | Modification of blood type antigens |
JP2023511408A (ja) | 2020-01-23 | 2023-03-17 | ザ チルドレンズ メディカル センター コーポレーション | ヒト多能性幹細胞からのストロマフリーt細胞分化法 |
EP3872190A1 (en) | 2020-02-26 | 2021-09-01 | Antibodies-Online GmbH | A method of using cut&run or cut&tag to validate crispr-cas targeting |
AU2021234302A1 (en) | 2020-03-11 | 2022-11-10 | Omega Therapeutics, Inc. | Compositions and methods for modulating forkhead box p3 (foxp3) gene expression |
BR112022018795A2 (pt) | 2020-03-20 | 2023-01-10 | Inst Nat Sante Rech Med | Receptor de antígeno quimérico específico para cd45rc humano e usos dos mesmos |
CA3177051A1 (en) | 2020-03-31 | 2021-10-07 | Metagenomi, Inc. | Class ii, type ii crispr systems |
US20210319851A1 (en) | 2020-04-03 | 2021-10-14 | Creyon Bio, Inc. | Oligonucleotide-based machine learning |
US11433121B1 (en) | 2020-04-03 | 2022-09-06 | National Technology & Engineering Solutions Of Sandia, Llc | Lipid composition for the delivery of therapeutic cargos |
WO2021216622A1 (en) | 2020-04-21 | 2021-10-28 | Aspen Neuroscience, Inc. | Gene editing of gba1 in stem cells and method of use of cells differentiated therefrom |
WO2021216623A1 (en) | 2020-04-21 | 2021-10-28 | Aspen Neuroscience, Inc. | Gene editing of lrrk2 in stem cells and method of use of cells differentiated therefrom |
WO2021217082A1 (en) | 2020-04-23 | 2021-10-28 | Genedit Inc. | Polymer with cationic and hydrophobic side chains |
KR20230002481A (ko) * | 2020-04-24 | 2023-01-05 | 기초과학연구원 | Cas9 또는 cas9 변이체를 이용한 유전체 교정 |
US20230172987A1 (en) | 2020-05-04 | 2023-06-08 | Iovance Biotherapeutics, Inc. | Processes for production of tumor infiltrating lymphocytes and uses of the same in immunotherapy |
WO2021224633A1 (en) | 2020-05-06 | 2021-11-11 | Orchard Therapeutics (Europe) Limited | Treatment for neurodegenerative diseases |
EP4146804A1 (en) * | 2020-05-08 | 2023-03-15 | The Broad Institute Inc. | Methods and compositions for simultaneous editing of both strands of a target double-stranded nucleotide sequence |
UY39237A (es) | 2020-05-29 | 2021-12-31 | Kws Saat Se & Co Kgaa | Inducción de haploides en plantas |
WO2021245435A1 (en) | 2020-06-03 | 2021-12-09 | Vilmorin & Cie | Melon plants resistant to scab disease, aphids and powdery mildew |
CA3186284A1 (en) | 2020-06-05 | 2021-12-09 | Vilmorin & Cie | Resistance in plants of solanum lycopersicum to the tobrfv |
US20230332104A1 (en) | 2020-06-11 | 2023-10-19 | Novartis Ag | Zbtb32 inhibitors and uses thereof |
US20230323299A1 (en) | 2020-08-03 | 2023-10-12 | Inserm (Institut National De La Santé Et De La Recherch Médicale) | Population of treg cells functionally committed to exert a regulatory activity and their use for adoptive therapy |
EP4192952A1 (en) | 2020-08-10 | 2023-06-14 | Novartis AG | Treatments for retinal degenerative diseases |
KR20230051677A (ko) | 2020-08-20 | 2023-04-18 | 에이투 바이오쎄라퓨틱스, 인크. | 메소텔린 양성 암을 치료하기 위한 조성물 및 방법 |
JP2023538116A (ja) | 2020-08-20 | 2023-09-06 | エー2 バイオセラピューティクス, インコーポレイテッド | Egfr陽性がんを治療するための組成物及び方法 |
EP4097486A4 (en) | 2020-08-20 | 2023-09-06 | A2 Biotherapeutics, Inc. | COMPOSITIONS AND METHODS OF TREATMENT OF POSITIVE CANCERS AT CEACAM |
CN116322313A (zh) | 2020-10-02 | 2023-06-23 | 维尔莫林公司 | 保质期延长的甜瓜 |
US20230372397A1 (en) | 2020-10-06 | 2023-11-23 | Iovance Biotherapeutics, Inc. | Treatment of nsclc patients with tumor infiltrating lymphocyte therapies |
WO2022076606A1 (en) | 2020-10-06 | 2022-04-14 | Iovance Biotherapeutics, Inc. | Treatment of nsclc patients with tumor infiltrating lymphocyte therapies |
EP4243608A1 (en) | 2020-11-11 | 2023-09-20 | Leibniz-Institut für Pflanzenbiochemie (IPB) | Fusion protein for editing endogenous dna of a eukaryotic cell |
AU2021378316A1 (en) | 2020-11-13 | 2023-06-01 | Novartis Ag | Combination therapies with chimeric antigen receptor (car)-expressing cells |
EP4001429A1 (en) | 2020-11-16 | 2022-05-25 | Antibodies-Online GmbH | Analysis of crispr-cas binding and cleavage sites followed by high-throughput sequencing (abc-seq) |
EP4255172A1 (en) | 2020-12-03 | 2023-10-11 | Vilmorin & Cie | Tomato plants resistant to tobrfv, tmv, tomv and tommv and corresponding resistance genes |
WO2022133149A1 (en) | 2020-12-17 | 2022-06-23 | Iovance Biotherapeutics, Inc. | Treatment of cancers with tumor infiltrating lymphocytes |
EP4262811A1 (en) | 2020-12-17 | 2023-10-25 | Iovance Biotherapeutics, Inc. | Treatment with tumor infiltrating lymphocyte therapies in combination with ctla-4 and pd-1 inhibitors |
EP4267157A1 (en) | 2020-12-23 | 2023-11-01 | Flagship Pioneering Innovations V, Inc. | In vitro assembly of anellovirus capsids enclosing rna |
EP4284919A1 (en) | 2021-01-29 | 2023-12-06 | Iovance Biotherapeutics, Inc. | Methods of making modified tumor infiltrating lymphocytes and their use in adoptive cell therapy |
MX2023009581A (es) | 2021-02-16 | 2023-08-23 | A2 Biotherapeutics Inc | Composiciones y metodos para tratar tipos de cancer her2 positivos. |
GB202103131D0 (en) | 2021-03-05 | 2021-04-21 | Biosystems Tech Limited | Method for preparation of research organisms |
TW202304480A (zh) | 2021-03-19 | 2023-02-01 | 美商艾歐凡斯生物治療公司 | 腫瘤浸潤淋巴球(til)中之與cd39/cd69選擇及基因剔除相關之til擴增之方法 |
KR20240009393A (ko) | 2021-03-31 | 2024-01-22 | 엔트라다 테라퓨틱스, 인크. | 사이클릭 세포 침투 펩티드 |
WO2022208489A1 (en) | 2021-04-02 | 2022-10-06 | Vilmorin & Cie | Semi-determinate or determinate growth habit trait in cucurbita |
AU2022263418A1 (en) | 2021-04-19 | 2023-10-26 | Iovance Biotherapeutics, Inc. | Chimeric costimulatory receptors, chemokine receptors, and the use of same in cellular immunotherapies |
WO2022232638A2 (en) * | 2021-04-30 | 2022-11-03 | Metagenomi, Inc. | Enzymes with ruvc domains |
CA3217862A1 (en) | 2021-05-05 | 2022-11-10 | Radius Pharmaceuticals, Inc. | Animal model having homologous recombination of mouse pth1 receptor |
EP4337263A1 (en) | 2021-05-10 | 2024-03-20 | Entrada Therapeutics, Inc. | Compositions and methods for modulating interferon regulatory factor-5 (irf-5) activity |
CA3218805A1 (en) | 2021-05-10 | 2022-11-17 | Ziqing QIAN | Compositions and methods for intracellular therapeutics |
JP2024518476A (ja) | 2021-05-10 | 2024-05-01 | エントラーダ セラピューティクス,インコーポレイティド | mRNAスプライシングを調節するための組成物及び方法 |
EP4340850A1 (en) | 2021-05-17 | 2024-03-27 | Iovance Biotherapeutics, Inc. | Pd-1 gene-edited tumor infiltrating lymphocytes and uses of same in immunotherapy |
EP4347818A2 (en) | 2021-06-01 | 2024-04-10 | Arbor Biotechnologies, Inc. | Gene editing systems comprising a crispr nuclease and uses thereof |
WO2022261561A1 (en) | 2021-06-11 | 2022-12-15 | Genedit Inc. | Biodegradable polymer comprising side chains with polyamine and polyalkylene oxide groups |
WO2022271818A1 (en) | 2021-06-23 | 2022-12-29 | Entrada Therapeutics, Inc. | Antisense compounds and methods for targeting cug repeats |
WO2023279118A2 (en) * | 2021-07-02 | 2023-01-05 | University Of Maryland, College Park | Cytidine deaminases and methods of genome editing using the same |
WO2023283359A2 (en) | 2021-07-07 | 2023-01-12 | Omega Therapeutics, Inc. | Compositions and methods for modulating secreted frizzled receptor protein 1 (sfrp1) gene expression |
EP4373270A2 (en) | 2021-07-22 | 2024-05-29 | Iovance Biotherapeutics, Inc. | Method for cryopreservation of solid tumor fragments |
CA3226942A1 (en) | 2021-07-28 | 2023-02-02 | Iovance Biotherapeutics, Inc. | Treatment of cancer patients with tumor infiltrating lymphocyte therapies in combination with kras inhibitors |
AR126622A1 (es) | 2021-07-30 | 2023-10-25 | Kws Saat Se & Co Kgaa | Plantas con digestibilidad mejorada y haplotipos marcadores |
EP4380353A1 (en) | 2021-08-06 | 2024-06-12 | Vilmorin & Cie | Resistance to leveillula taurica in pepper |
EP4396357A1 (en) | 2021-09-02 | 2024-07-10 | SESVanderHave NV | Methods and compositions for ppo herbicide tolerance |
JP7125727B1 (ja) | 2021-09-07 | 2022-08-25 | 国立大学法人千葉大学 | 核酸配列改変用組成物および核酸配列の標的部位を改変する方法 |
IL311225A (en) * | 2021-09-08 | 2024-05-01 | Flagship Pioneering Innovations Vi Llc | Methods and compositions for genome modulation |
WO2023039586A1 (en) | 2021-09-10 | 2023-03-16 | Agilent Technologies, Inc. | Guide rnas with chemical modification for prime editing |
CA3232376A1 (en) | 2021-09-20 | 2023-03-23 | Maria KOKKINAKI | Multitransgenic pigs comprising ten genetic modifications for xenotransplantation |
CN118119707A (zh) | 2021-09-30 | 2024-05-31 | 阿斯利康(瑞典)有限公司 | 抑制剂增加CRISPR/Cas插入效率的用途 |
WO2023060132A1 (en) * | 2021-10-05 | 2023-04-13 | The J. David Gladstone Institutes, A Testamentary Trust Established Under The Will Of J. David Gladstone | Allele specific editing to treat fus-induced neurodegeneration |
CA3233824A1 (en) | 2021-10-08 | 2023-04-13 | Samir Mitragotri | Ionic liquids for drug delivery |
AR127482A1 (es) | 2021-10-27 | 2024-01-31 | Iovance Biotherapeutics Inc | Sistemas y métodos para coordinar la fabricación de células para inmunoterapia específica de paciente |
IL312452A (en) | 2021-11-01 | 2024-06-01 | Tome Biosciences Inc | A transformant has a single structure for the simultaneous transfer of a gene editing mechanism and a nucleic acid cargo |
CA3237482A1 (en) | 2021-11-03 | 2023-05-11 | The J. David Gladstone Institutes, A Testamentary Trust Established Under The Will Of J. David Gladstone | Precise genome editing using retrons |
WO2023086803A1 (en) | 2021-11-10 | 2023-05-19 | Iovance Biotherapeutics, Inc. | Methods of expansion treatment utilizing cd8 tumor infiltrating lymphocytes |
EP4389902A1 (en) | 2021-11-15 | 2024-06-26 | National University Corporation Tottori University | Method for producing human artificial chromosome vector in human cells |
WO2023093862A1 (en) | 2021-11-26 | 2023-06-01 | Epigenic Therapeutics Inc. | Method of modulating pcsk9 and uses thereof |
GB202118058D0 (en) | 2021-12-14 | 2022-01-26 | Univ Warwick | Methods to increase yields in crops |
US20230279442A1 (en) | 2021-12-15 | 2023-09-07 | Versitech Limited | Engineered cas9-nucleases and method of use thereof |
TW202342757A (zh) | 2021-12-17 | 2023-11-01 | 美商薩那生物科技公司 | 經修飾副黏液病毒科附著醣蛋白 |
TW202342498A (zh) | 2021-12-17 | 2023-11-01 | 美商薩那生物科技公司 | 經修飾副黏液病毒科融合醣蛋白 |
WO2023122764A1 (en) | 2021-12-22 | 2023-06-29 | Tome Biosciences, Inc. | Co-delivery of a gene editor construct and a donor template |
CA3240593A1 (en) | 2021-12-23 | 2023-06-29 | Joel D. Richter | Therapeutic treatment for fragile x-associated disorder |
WO2023133595A2 (en) | 2022-01-10 | 2023-07-13 | Sana Biotechnology, Inc. | Methods of ex vivo dosing and administration of lipid particles or viral vectors and related systems and uses |
WO2023141602A2 (en) | 2022-01-21 | 2023-07-27 | Renagade Therapeutics Management Inc. | Engineered retrons and methods of use |
WO2023147488A1 (en) | 2022-01-28 | 2023-08-03 | Iovance Biotherapeutics, Inc. | Cytokine associated tumor infiltrating lymphocytes compositions and methods |
WO2023150518A1 (en) | 2022-02-01 | 2023-08-10 | Sana Biotechnology, Inc. | Cd3-targeted lentiviral vectors and uses thereof |
WO2023150647A1 (en) | 2022-02-02 | 2023-08-10 | Sana Biotechnology, Inc. | Methods of repeat dosing and administration of lipid particles or viral vectors and related systems and uses |
WO2023156587A1 (en) | 2022-02-18 | 2023-08-24 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Use of tcr-deficient car-tregs in combination with anti-tcr complex monoclonal antibodies for inducing durable tolerance |
WO2023196877A1 (en) | 2022-04-06 | 2023-10-12 | Iovance Biotherapeutics, Inc. | Treatment of nsclc patients with tumor infiltrating lymphocyte therapies |
EP4256950A1 (en) | 2022-04-06 | 2023-10-11 | Vilmorin et Cie | Tolerance to cgmmv in cucumber |
WO2023201369A1 (en) | 2022-04-15 | 2023-10-19 | Iovance Biotherapeutics, Inc. | Til expansion processes using specific cytokine combinations and/or akti treatment |
WO2023205744A1 (en) | 2022-04-20 | 2023-10-26 | Tome Biosciences, Inc. | Programmable gene insertion compositions |
WO2023215831A1 (en) | 2022-05-04 | 2023-11-09 | Tome Biosciences, Inc. | Guide rna compositions for programmable gene insertion |
WO2023220043A1 (en) | 2022-05-09 | 2023-11-16 | Synteny Therapeutics, Inc. | Erythroparvovirus with a modified genome for gene therapy |
WO2023219933A1 (en) | 2022-05-09 | 2023-11-16 | Entrada Therapeutics, Inc. | Compositions and methods for delivery of nucleic acid therapeutics |
WO2023220035A1 (en) | 2022-05-09 | 2023-11-16 | Synteny Therapeutics, Inc. | Erythroparvovirus compositions and methods for gene therapy |
WO2023220040A1 (en) | 2022-05-09 | 2023-11-16 | Synteny Therapeutics, Inc. | Erythroparvovirus with a modified capsid for gene therapy |
WO2023220608A1 (en) | 2022-05-10 | 2023-11-16 | Iovance Biotherapeutics, Inc. | Treatment of cancer patients with tumor infiltrating lymphocyte therapies in combination with an il-15r agonist |
WO2023225670A2 (en) | 2022-05-20 | 2023-11-23 | Tome Biosciences, Inc. | Ex vivo programmable gene insertion |
WO2023230566A2 (en) | 2022-05-25 | 2023-11-30 | Flagship Pioneering Innovations Vii, Llc | Compositions and methods for modulating cytokines |
WO2023230549A2 (en) | 2022-05-25 | 2023-11-30 | Flagship Pioneering Innovations Vii, Llc | Compositions and methods for modulation of tumor suppressors and oncogenes |
WO2023230570A2 (en) | 2022-05-25 | 2023-11-30 | Flagship Pioneering Innovations Vii, Llc | Compositions and methods for modulating genetic drivers |
WO2023230573A2 (en) | 2022-05-25 | 2023-11-30 | Flagship Pioneering Innovations Vii, Llc | Compositions and methods for modulation of immune responses |
WO2023230578A2 (en) | 2022-05-25 | 2023-11-30 | Flagship Pioneering Innovations Vii, Llc | Compositions and methods for modulating circulating factors |
GB2621813A (en) | 2022-06-30 | 2024-02-28 | Univ Newcastle | Preventing disease recurrence in Mitochondrial replacement therapy |
EP4299733A1 (en) | 2022-06-30 | 2024-01-03 | Inari Agriculture Technology, Inc. | Compositions, systems, and methods for genome editing |
WO2024005863A1 (en) | 2022-06-30 | 2024-01-04 | Inari Agriculture Technology, Inc. | Compositions, systems, and methods for genome editing |
EP4299739A1 (en) | 2022-06-30 | 2024-01-03 | Inari Agriculture Technology, Inc. | Compositions, systems, and methods for genome editing |
WO2024005864A1 (en) | 2022-06-30 | 2024-01-04 | Inari Agriculture Technology, Inc. | Compositions, systems, and methods for genome editing |
WO2024020346A2 (en) | 2022-07-18 | 2024-01-25 | Renagade Therapeutics Management Inc. | Gene editing components, systems, and methods of use |
WO2024020587A2 (en) | 2022-07-22 | 2024-01-25 | Tome Biosciences, Inc. | Pleiopluripotent stem cell programmable gene insertion |
WO2024023734A1 (en) | 2022-07-26 | 2024-02-01 | Bit Bio Limited | MULTI-gRNA GENOME EDITING |
WO2024030930A2 (en) * | 2022-08-01 | 2024-02-08 | The Johns Hopkins University | Compositions and methods for modifying muller glial cells |
WO2024040222A1 (en) | 2022-08-19 | 2024-02-22 | Generation Bio Co. | Cleavable closed-ended dna (cedna) and methods of use thereof |
WO2024044655A1 (en) | 2022-08-24 | 2024-02-29 | Sana Biotechnology, Inc. | Delivery of heterologous proteins |
WO2024044723A1 (en) | 2022-08-25 | 2024-02-29 | Renagade Therapeutics Management Inc. | Engineered retrons and methods of use |
WO2024042199A1 (en) | 2022-08-26 | 2024-02-29 | KWS SAAT SE & Co. KGaA | Use of paired genes in hybrid breeding |
WO2024047587A1 (en) | 2022-08-31 | 2024-03-07 | Regel Therapeutics, Inc. | Cas-phi compositions and methods of use |
WO2024050544A2 (en) | 2022-09-01 | 2024-03-07 | J.R. Simplot Company | Enhanced targeted knock-in frequency in host genomes through crispr exonuclease processing |
WO2024047605A1 (en) | 2022-09-01 | 2024-03-07 | SESVanderHave NV | Methods and compositions for ppo herbicide tolerance |
WO2024052318A1 (en) | 2022-09-06 | 2024-03-14 | Institut National de la Santé et de la Recherche Médicale | Novel dual split car-t cells for the treatment of cd38-positive hematological malignancies |
WO2024064838A1 (en) | 2022-09-21 | 2024-03-28 | Sana Biotechnology, Inc. | Lipid particles comprising variant paramyxovirus attachment glycoproteins and uses thereof |
WO2024074888A2 (en) | 2022-10-03 | 2024-04-11 | The Regents Of The University Of California | Circumventing barriers to hybrid crops from genetically distant crosses |
WO2024081820A1 (en) | 2022-10-13 | 2024-04-18 | Sana Biotechnology, Inc. | Viral particles targeting hematopoietic stem cells |
WO2024098027A1 (en) | 2022-11-04 | 2024-05-10 | Iovance Biotherapeutics, Inc. | Methods for tumor infiltrating lymphocyte (til) expansion related to cd39/cd103 selection |
WO2024098024A1 (en) | 2022-11-04 | 2024-05-10 | Iovance Biotherapeutics, Inc. | Expansion of tumor infiltrating lymphocytes from liquid tumors and therapeutic uses thereof |
WO2024102434A1 (en) | 2022-11-10 | 2024-05-16 | Senda Biosciences, Inc. | Rna compositions comprising lipid nanoparticles or lipid reconstructed natural messenger packs |
WO2024112571A2 (en) | 2022-11-21 | 2024-05-30 | Iovance Biotherapeutics, Inc. | Two-dimensional processes for the expansion of tumor infiltrating lymphocytes and therapies therefrom |
WO2024118836A1 (en) | 2022-11-30 | 2024-06-06 | Iovance Biotherapeutics, Inc. | Processes for production of tumor infiltrating lymphocytes with shortened rep step |
WO2024119157A1 (en) | 2022-12-02 | 2024-06-06 | Sana Biotechnology, Inc. | Lipid particles with cofusogens and methods of producing and using the same |
WO2024138194A1 (en) | 2022-12-22 | 2024-06-27 | Tome Biosciences, Inc. | Platforms, compositions, and methods for in vivo programmable gene insertion |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP6395765B2 (ja) * | 2012-12-12 | 2018-09-26 | ザ・ブロード・インスティテュート・インコーポレイテッド | 配列操作のための改善された系、方法および酵素組成物のエンジニアリングおよび最適化 |
Family Cites Families (63)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4217344A (en) | 1976-06-23 | 1980-08-12 | L'oreal | Compositions containing aqueous dispersions of lipid spheres |
US4235871A (en) | 1978-02-24 | 1980-11-25 | Papahadjopoulos Demetrios P | Method of encapsulating biologically active materials in lipid vesicles |
US4186183A (en) | 1978-03-29 | 1980-01-29 | The United States Of America As Represented By The Secretary Of The Army | Liposome carriers in chemotherapy of leishmaniasis |
US4261975A (en) | 1979-09-19 | 1981-04-14 | Merck & Co., Inc. | Viral liposome particle |
US4485054A (en) | 1982-10-04 | 1984-11-27 | Lipoderm Pharmaceuticals Limited | Method of encapsulating biologically active materials in multilamellar lipid vesicles (MLV) |
US4501728A (en) | 1983-01-06 | 1985-02-26 | Technology Unlimited, Inc. | Masking of liposomes from RES recognition |
US4946787A (en) | 1985-01-07 | 1990-08-07 | Syntex (U.S.A.) Inc. | N-(ω,(ω-1)-dialkyloxy)- and N-(ω,(ω-1)-dialkenyloxy)-alk-1-yl-N,N,N-tetrasubstituted ammonium lipids and uses therefor |
US4897355A (en) | 1985-01-07 | 1990-01-30 | Syntex (U.S.A.) Inc. | N[ω,(ω-1)-dialkyloxy]- and N-[ω,(ω-1)-dialkenyloxy]-alk-1-yl-N,N,N-tetrasubstituted ammonium lipids and uses therefor |
US5049386A (en) | 1985-01-07 | 1991-09-17 | Syntex (U.S.A.) Inc. | N-ω,(ω-1)-dialkyloxy)- and N-(ω,(ω-1)-dialkenyloxy)Alk-1-YL-N,N,N-tetrasubstituted ammonium lipids and uses therefor |
US4797368A (en) | 1985-03-15 | 1989-01-10 | The United States Of America As Represented By The Department Of Health And Human Services | Adeno-associated virus as eukaryotic expression vector |
US4774085A (en) | 1985-07-09 | 1988-09-27 | 501 Board of Regents, Univ. of Texas | Pharmaceutical administration systems containing a mixture of immunomodulators |
EP0264166B1 (en) | 1986-04-09 | 1996-08-21 | Genzyme Corporation | Transgenic animals secreting desired proteins into milk |
US4837028A (en) | 1986-12-24 | 1989-06-06 | Liposome Technology, Inc. | Liposomes with enhanced circulation time |
US4873316A (en) | 1987-06-23 | 1989-10-10 | Biogen, Inc. | Isolation of exogenous recombinant proteins from the milk of transgenic mammals |
US5143854A (en) | 1989-06-07 | 1992-09-01 | Affymax Technologies N.V. | Large scale photolithographic solid phase synthesis of polypeptides and receptor binding screening thereof |
US5264618A (en) | 1990-04-19 | 1993-11-23 | Vical, Inc. | Cationic lipids for intracellular delivery of biologically active molecules |
AU7979491A (en) | 1990-05-03 | 1991-11-27 | Vical, Inc. | Intracellular delivery of biologically active substances by means of self-assembling lipid complexes |
US5210015A (en) | 1990-08-06 | 1993-05-11 | Hoffman-La Roche Inc. | Homogeneous assay system using the nuclease activity of a nucleic acid polymerase |
US5173414A (en) | 1990-10-30 | 1992-12-22 | Applied Immune Sciences, Inc. | Production of recombinant adeno-associated virus vectors |
US7150982B2 (en) | 1991-09-09 | 2006-12-19 | Third Wave Technologies, Inc. | RNA detection assays |
US5587308A (en) | 1992-06-02 | 1996-12-24 | The United States Of America As Represented By The Department Of Health & Human Services | Modified adeno-associated virus vector capable of expression from a novel promoter |
EP0831854A4 (en) | 1995-06-06 | 2001-01-24 | Isis Pharmaceuticals Inc | OLIGONUCLEOTIDS WITH PHOSPHOROTHIOATE BINDINGS OF HIGH CHIRAL PURITY |
US5985662A (en) | 1995-07-13 | 1999-11-16 | Isis Pharmaceuticals Inc. | Antisense inhibition of hepatitis B virus replication |
IL135776A0 (en) | 1997-10-24 | 2001-05-20 | Life Technologies Inc | Recombinational cloning using nucleic acids having recombination sites |
US6750059B1 (en) | 1998-07-16 | 2004-06-15 | Whatman, Inc. | Archiving of vectors |
US6534261B1 (en) | 1999-01-12 | 2003-03-18 | Sangamo Biosciences, Inc. | Regulation of endogenous gene expression in cells using zinc finger proteins |
US7868149B2 (en) | 1999-07-20 | 2011-01-11 | Monsanto Technology Llc | Plant genome sequence and uses thereof |
US6603061B1 (en) | 1999-07-29 | 2003-08-05 | Monsanto Company | Agrobacterium-mediated plant transformation method |
AU2002336760A1 (en) | 2001-09-26 | 2003-06-10 | Mayo Foundation For Medical Education And Research | Mutable vaccines |
US20090100536A1 (en) | 2001-12-04 | 2009-04-16 | Monsanto Company | Transgenic plants with enhanced agronomic traits |
FR2862659B1 (fr) * | 2003-11-21 | 2006-02-10 | Pasteur Institut | Genome de legionella pneumophila souche paris- applications diagnostiques et epidemiologiques |
AU2005274948B2 (en) | 2004-07-16 | 2011-09-22 | Genvec, Inc. | Vaccines against aids comprising CMV/R-nucleic acid constructs |
CN101228176A (zh) * | 2005-04-28 | 2008-07-23 | 贝尼泰克有限公司 | 用于同时递送与杂合表达模式相关的RNAi因子的多重RNAi表达盒 |
EP2325332B1 (en) * | 2005-08-26 | 2012-10-31 | DuPont Nutrition Biosciences ApS | Use of CRISPR associated genes (CAS) |
WO2007106690A2 (en) | 2006-03-15 | 2007-09-20 | Siemens Healthcare Diagnostics Inc. | Degenerate nucleobase analogs |
DK2126130T3 (en) | 2007-03-02 | 2015-06-29 | Dupont Nutrition Biosci Aps | CULTURES WITH IMPROVED phage resistance |
JP2011512326A (ja) | 2007-12-31 | 2011-04-21 | ナノコア セラピューティクス,インコーポレイテッド | 心不全の治療用のrna干渉 |
WO2010011961A2 (en) * | 2008-07-25 | 2010-01-28 | University Of Georgia Research Foundation, Inc. | Prokaryotic rnai-like system and methods of use |
US20100076057A1 (en) | 2008-09-23 | 2010-03-25 | Northwestern University | TARGET DNA INTERFERENCE WITH crRNA |
WO2010054108A2 (en) | 2008-11-06 | 2010-05-14 | University Of Georgia Research Foundation, Inc. | Cas6 polypeptides and methods of use |
US8586526B2 (en) | 2010-05-17 | 2013-11-19 | Sangamo Biosciences, Inc. | DNA-binding proteins and uses thereof |
WO2011028929A2 (en) | 2009-09-03 | 2011-03-10 | The Regents Of The University Of California | Nitrate-responsive promoter |
US8889394B2 (en) | 2009-09-07 | 2014-11-18 | Empire Technology Development Llc | Multiple domain proteins |
US10087431B2 (en) | 2010-03-10 | 2018-10-02 | The Regents Of The University Of California | Methods of generating nucleic acid fragments |
EP2569425B1 (en) | 2010-05-10 | 2016-07-06 | The Regents of The University of California | Endoribonuclease compositions and methods of use thereof |
US9405700B2 (en) | 2010-11-04 | 2016-08-02 | Sonics, Inc. | Methods and apparatus for virtualization in an integrated circuit |
US20140113376A1 (en) | 2011-06-01 | 2014-04-24 | Rotem Sorek | Compositions and methods for downregulating prokaryotic genes |
GB201122458D0 (en) | 2011-12-30 | 2012-02-08 | Univ Wageningen | Modified cascade ribonucleoproteins and uses thereof |
WO2013141680A1 (en) * | 2012-03-20 | 2013-09-26 | Vilnius University | RNA-DIRECTED DNA CLEAVAGE BY THE Cas9-crRNA COMPLEX |
US9637739B2 (en) * | 2012-03-20 | 2017-05-02 | Vilnius University | RNA-directed DNA cleavage by the Cas9-crRNA complex |
DK3401400T3 (da) | 2012-05-25 | 2019-06-03 | Univ California | Fremgangsmåder og sammensætninger til rna-styret mål-dna-modifikation og til rna-styret transskriptionsmodulering |
CN110643600A (zh) | 2012-10-23 | 2020-01-03 | 基因工具股份有限公司 | 用于切割靶dna的系统及其用途 |
JP6620018B2 (ja) | 2012-12-06 | 2019-12-11 | シグマ−アルドリッチ・カンパニー・リミテッド・ライアビリティ・カンパニーSigma−Aldrich Co., LLC | Crisprに基づくゲノム修飾および制御 |
WO2014093479A1 (en) | 2012-12-11 | 2014-06-19 | Montana State University | Crispr (clustered regularly interspaced short palindromic repeats) rna-guided control of gene regulation |
MX2015007550A (es) | 2012-12-12 | 2017-02-02 | Broad Inst Inc | Suministro, modificación y optimización de sistemas, métodos y composiciones para la manipulación de secuencias y aplicaciones terapéuticas. |
US20140186843A1 (en) | 2012-12-12 | 2014-07-03 | Massachusetts Institute Of Technology | Methods, systems, and apparatus for identifying target sequences for cas enzymes or crispr-cas systems for target sequences and conveying results thereof |
US8993233B2 (en) | 2012-12-12 | 2015-03-31 | The Broad Institute Inc. | Engineering and optimization of systems, methods and compositions for sequence manipulation with functional domains |
PT2896697E (pt) | 2012-12-12 | 2015-12-31 | Massachusetts Inst Technology | Engenharia de sistemas, métodos e composições guia otimizadas para a manipulação de sequências |
US8697359B1 (en) | 2012-12-12 | 2014-04-15 | The Broad Institute, Inc. | CRISPR-Cas systems and methods for altering expression of gene products |
WO2014093709A1 (en) | 2012-12-12 | 2014-06-19 | The Broad Institute, Inc. | Methods, models, systems, and apparatus for identifying target sequences for cas enzymes or crispr-cas systems for target sequences and conveying results thereof |
CN105658796B (zh) | 2012-12-12 | 2021-10-26 | 布罗德研究所有限公司 | 用于序列操纵的crispr-cas组分系统、方法以及组合物 |
WO2014093701A1 (en) | 2012-12-12 | 2014-06-19 | The Broad Institute, Inc. | Functional genomics using crispr-cas systems, compositions, methods, knock out libraries and applications thereof |
EP3553174A1 (en) | 2012-12-17 | 2019-10-16 | President and Fellows of Harvard College | Rna-guided human genome engineering |
-
2013
- 2013-12-12 PT PT138143649T patent/PT2898075E/pt unknown
- 2013-12-12 DK DK16151694.3T patent/DK3064585T3/da active
- 2013-12-12 SG SG10201912327SA patent/SG10201912327SA/en unknown
- 2013-12-12 CN CN202110502128.8A patent/CN113355357A/zh active Pending
- 2013-12-12 SG SG11201504519TA patent/SG11201504519TA/en unknown
- 2013-12-12 JP JP2015547545A patent/JP6552965B2/ja active Active
- 2013-12-12 CN CN201380072821.XA patent/CN105209621B/zh active Active
- 2013-12-12 DK DK13814364.9T patent/DK2898075T3/en active
- 2013-12-12 CA CA2894684A patent/CA2894684A1/en active Pending
- 2013-12-12 WO PCT/US2013/074691 patent/WO2014093635A1/en active Application Filing
- 2013-12-12 ES ES13814364.9T patent/ES2576126T3/es active Active
- 2013-12-12 ES ES16151694T patent/ES2786193T3/es active Active
- 2013-12-12 EP EP13814364.9A patent/EP2898075B1/en active Active
- 2013-12-12 KR KR1020157018660A patent/KR20150105634A/ko unknown
- 2013-12-12 SG SG10201801969TA patent/SG10201801969TA/en unknown
- 2013-12-12 PL PL13814364.9T patent/PL2898075T3/pl unknown
- 2013-12-12 US US14/104,977 patent/US20140186919A1/en not_active Abandoned
- 2013-12-12 AU AU2013359212A patent/AU2013359212B2/en active Active
- 2013-12-12 IL IL300461A patent/IL300461A/en unknown
-
2014
- 2014-03-24 US US14/222,930 patent/US8865406B2/en active Active
- 2014-06-02 US US14/293,674 patent/US8889418B2/en active Active
- 2014-06-02 US US14/293,498 patent/US8895308B1/en active Active
-
2015
- 2015-06-05 ZA ZA2015/04081A patent/ZA201504081B/en unknown
- 2015-06-10 IL IL239315A patent/IL239315B2/en unknown
- 2015-08-13 HK HK15107819.7A patent/HK1207119A1/zh unknown
-
2016
- 2016-07-01 JP JP2016131404A patent/JP6395765B2/ja active Active
- 2016-11-07 US US15/330,876 patent/US20170198269A1/en active Pending
-
2017
- 2017-04-19 AU AU2017202542A patent/AU2017202542B2/en active Active
-
2018
- 2018-06-25 JP JP2018119670A patent/JP6665230B2/ja active Active
-
2019
- 2019-09-23 AU AU2019236591A patent/AU2019236591B2/en active Active
-
2020
- 2020-02-18 JP JP2020025253A patent/JP7125440B2/ja active Active
-
2022
- 2022-03-24 AU AU2022202048A patent/AU2022202048A1/en active Pending
- 2022-06-07 JP JP2022092414A patent/JP2022113766A/ja active Pending
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP6395765B2 (ja) * | 2012-12-12 | 2018-09-26 | ザ・ブロード・インスティテュート・インコーポレイテッド | 配列操作のための改善された系、方法および酵素組成物のエンジニアリングおよび最適化 |
Non-Patent Citations (5)
Title |
---|
CONG, LE ET AL.: ""Multiplex genome engineering using CRISPR/Cas systems"", SCIENCE, vol. 339, JPN6016034409, 2013, pages 819 - 823, XP055871219, ISSN: 0004054243, DOI: 10.1126/science.1231143 * |
JINEK, MARTIN ET AL.: ""A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity"", SCIENCE, vol. 337, JPN6016021641, 2012, pages 816 - 821, XP093068947, ISSN: 0004054246, DOI: 10.1126/science.1225829 * |
KINNEVERY, PETER M. ET AL.: ""Emergence of sequence type 779 methicillin-resistant Staphylococcus aureus harboring a novel pseudo", ANTIMICROB. AGENTS CHEMOTHER., vol. 57, JPN6016034415, 2013, pages 524 - 531, XP055338796, ISSN: 0004054244, DOI: 10.1128/AAC.01689-12 * |
MALI, PRASHANT ET AL.: ""RNA-guided human genome engineering via Cas9"", SCIENCE, vol. 339, JPN6016034412, 2013, pages 823 - 826, ISSN: 0004054242 * |
STAPHYLOCOCCUS AUREUS SUBSP. AUREUS ORFX GENE AND PSEUDO SCCMEC-SCC-SCCCRISPR ELEMENT, STRAIN M06/01, JPN6016034417, ISSN: 0004054245 * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPWO2020067004A1 (ja) * | 2018-09-25 | 2021-08-30 | 公益財団法人微生物化学研究会 | 新規ウイルスベクターおよびその製造方法と使用方法 |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6665230B2 (ja) | 配列操作のための改善された系、方法および酵素組成物のエンジニアリングおよび最適化 | |
JP7198328B2 (ja) | 配列操作のための系、方法および最適化ガイド組成物のエンジニアリング | |
JP7383062B2 (ja) | 配列操作のための最適化されたCRISPR-Cas二重ニッカーゼ系、方法および組成物 | |
JP6870015B2 (ja) | 遺伝子産物の発現を変更するためのCRISPR−Cas系および方法 | |
JP6625971B2 (ja) | 配列操作のためのタンデムガイド系、方法および組成物の送達、エンジニアリングおよび最適化 | |
DK2931898T3 (en) | CONSTRUCTION AND OPTIMIZATION OF SYSTEMS, PROCEDURES AND COMPOSITIONS FOR SEQUENCE MANIPULATION WITH FUNCTIONAL DOMAINS | |
JP2020511931A (ja) | 改良された遺伝子編集 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20180717 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20190405 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20190617 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20190823 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20191217 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20200120 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20200219 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6665230 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
RD03 | Notification of appointment of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: R3D03 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |