KR20180134412A - 전사 인자 4에서 트라이뉴클레오타이드 반복부와 연관된 질환의 치료를 위한 조성물 및 방법 - Google Patents
전사 인자 4에서 트라이뉴클레오타이드 반복부와 연관된 질환의 치료를 위한 조성물 및 방법 Download PDFInfo
- Publication number
- KR20180134412A KR20180134412A KR1020187033525A KR20187033525A KR20180134412A KR 20180134412 A KR20180134412 A KR 20180134412A KR 1020187033525 A KR1020187033525 A KR 1020187033525A KR 20187033525 A KR20187033525 A KR 20187033525A KR 20180134412 A KR20180134412 A KR 20180134412A
- Authority
- KR
- South Korea
- Prior art keywords
- seq
- nuclease
- guide rna
- sequence
- grna
- 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.)
- Ceased
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 355
- 238000000034 method Methods 0.000 title claims abstract description 93
- 108010048992 Transcription Factor 4 Proteins 0.000 title claims description 71
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims description 36
- 201000010099 disease Diseases 0.000 title claims description 30
- 102000009523 Transcription Factor 4 Human genes 0.000 title description 69
- 230000035772 mutation Effects 0.000 claims abstract description 111
- 108010035532 Collagen Proteins 0.000 claims abstract description 23
- 102000008186 Collagen Human genes 0.000 claims abstract description 23
- 229920001436 collagen Polymers 0.000 claims abstract description 23
- 102100023489 Transcription factor 4 Human genes 0.000 claims abstract 5
- 101000976959 Homo sapiens Transcription factor 4 Proteins 0.000 claims abstract 3
- 101000596771 Homo sapiens Transcription factor 7-like 2 Proteins 0.000 claims abstract 3
- 108020005004 Guide RNA Proteins 0.000 claims description 1000
- 101710163270 Nuclease Proteins 0.000 claims description 226
- 108091032973 (ribonucleotides)n+m Proteins 0.000 claims description 222
- 125000003729 nucleotide group Chemical group 0.000 claims description 140
- 150000002632 lipids Chemical class 0.000 claims description 137
- 239000002773 nucleotide Substances 0.000 claims description 137
- 108090000623 proteins and genes Proteins 0.000 claims description 128
- 239000013598 vector Substances 0.000 claims description 101
- 102000004169 proteins and genes Human genes 0.000 claims description 87
- 208000033051 Fuchs endothelial corneal dystrophy Diseases 0.000 claims description 73
- 230000000295 complement effect Effects 0.000 claims description 70
- 108091033409 CRISPR Proteins 0.000 claims description 45
- 239000002105 nanoparticle Substances 0.000 claims description 39
- 101150017815 TCF4 gene Proteins 0.000 claims description 34
- 108700028369 Alleles Proteins 0.000 claims description 33
- 102220005941 rs80358192 Human genes 0.000 claims description 31
- 102220055955 rs727504229 Human genes 0.000 claims description 28
- 102200030577 rs80358191 Human genes 0.000 claims description 28
- 230000014509 gene expression Effects 0.000 claims description 27
- 101150030360 COL8A2 gene Proteins 0.000 claims description 20
- 101100114043 Homo sapiens COL8A2 gene Proteins 0.000 claims description 20
- 239000013603 viral vector Substances 0.000 claims description 19
- 239000003814 drug Substances 0.000 claims description 15
- 208000010157 sclerosing cholangitis Diseases 0.000 claims description 15
- 230000008859 change Effects 0.000 claims description 14
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 claims description 12
- 238000004519 manufacturing process Methods 0.000 claims description 11
- 239000008194 pharmaceutical composition Substances 0.000 claims description 10
- 230000009467 reduction Effects 0.000 claims description 10
- 230000006641 stabilisation Effects 0.000 claims description 9
- 238000011105 stabilization Methods 0.000 claims description 9
- 238000002054 transplantation Methods 0.000 claims description 9
- 230000006872 improvement Effects 0.000 claims description 7
- 238000005259 measurement Methods 0.000 claims description 7
- 239000003889 eye drop Substances 0.000 claims description 6
- 238000000386 microscopy Methods 0.000 claims description 6
- 239000002674 ointment Substances 0.000 claims description 6
- 229940035893 uracil Drugs 0.000 claims description 6
- 108010077850 Nuclear Localization Signals Proteins 0.000 claims description 4
- 230000004438 eyesight Effects 0.000 claims description 4
- 238000009472 formulation Methods 0.000 claims description 3
- 230000001105 regulatory effect Effects 0.000 claims description 3
- 238000010354 CRISPR gene editing Methods 0.000 claims description 2
- 108010008532 Deoxyribonuclease I Proteins 0.000 claims description 2
- 102000007260 Deoxyribonuclease I Human genes 0.000 claims description 2
- 101000854936 Homo sapiens Visual system homeobox 1 Proteins 0.000 claims description 2
- 102100020673 Visual system homeobox 1 Human genes 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 2
- 201000004207 posterior polymorphous corneal dystrophy Diseases 0.000 claims description 2
- 230000008685 targeting Effects 0.000 abstract description 29
- 208000006673 asthma Diseases 0.000 abstract description 10
- 230000003511 endothelial effect Effects 0.000 abstract description 4
- 108020004414 DNA Proteins 0.000 description 1134
- 150000007523 nucleic acids Chemical class 0.000 description 64
- 102000039446 nucleic acids Human genes 0.000 description 62
- 108020004707 nucleic acids Proteins 0.000 description 62
- 108091079001 CRISPR RNA Proteins 0.000 description 53
- 210000004027 cell Anatomy 0.000 description 49
- 230000004048 modification Effects 0.000 description 39
- 238000012986 modification Methods 0.000 description 39
- 206010057190 Respiratory tract infections Diseases 0.000 description 34
- 238000012217 deletion Methods 0.000 description 25
- 229920001223 polyethylene glycol Polymers 0.000 description 22
- -1 nucleic acid phosphodiester Chemical class 0.000 description 21
- 239000000047 product Substances 0.000 description 21
- 239000002202 Polyethylene glycol Substances 0.000 description 19
- 238000006467 substitution reaction Methods 0.000 description 19
- 241000700605 Viruses Species 0.000 description 17
- 235000000346 sugar Nutrition 0.000 description 17
- 230000037430 deletion Effects 0.000 description 16
- 102000004389 Ribonucleoproteins Human genes 0.000 description 15
- 108010081734 Ribonucleoproteins Proteins 0.000 description 15
- 230000006780 non-homologous end joining Effects 0.000 description 15
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 15
- 210000004087 cornea Anatomy 0.000 description 14
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 14
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 14
- 238000002679 ablation Methods 0.000 description 12
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 12
- 230000000694 effects Effects 0.000 description 12
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 12
- 238000003776 cleavage reaction Methods 0.000 description 11
- 230000000875 corresponding effect Effects 0.000 description 11
- 108020004999 messenger RNA Proteins 0.000 description 11
- 201000000742 primary sclerosing cholangitis Diseases 0.000 description 11
- 230000007017 scission Effects 0.000 description 11
- 206010008609 Cholangitis sclerosing Diseases 0.000 description 10
- 231100000419 toxicity Toxicity 0.000 description 10
- 230000001988 toxicity Effects 0.000 description 10
- 125000000217 alkyl group Chemical group 0.000 description 9
- 230000005782 double-strand break Effects 0.000 description 9
- 230000006801 homologous recombination Effects 0.000 description 9
- 238000002744 homologous recombination Methods 0.000 description 9
- 238000003780 insertion Methods 0.000 description 9
- 230000037431 insertion Effects 0.000 description 9
- 230000008569 process Effects 0.000 description 9
- SLKDGVPOSSLUAI-PGUFJCEWSA-N 1,2-dihexadecanoyl-sn-glycero-3-phosphoethanolamine zwitterion Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OCCN)OC(=O)CCCCCCCCCCCCCCC SLKDGVPOSSLUAI-PGUFJCEWSA-N 0.000 description 8
- 102000053602 DNA Human genes 0.000 description 8
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 8
- 108091028043 Nucleic acid sequence Proteins 0.000 description 8
- 230000002159 abnormal effect Effects 0.000 description 8
- 230000004075 alteration Effects 0.000 description 8
- 239000012634 fragment Substances 0.000 description 8
- 230000001965 increasing effect Effects 0.000 description 8
- 102000004190 Enzymes Human genes 0.000 description 7
- 108090000790 Enzymes Proteins 0.000 description 7
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
- 230000001939 inductive effect Effects 0.000 description 7
- 125000003835 nucleoside group Chemical group 0.000 description 7
- 208000024891 symptom Diseases 0.000 description 7
- 125000003275 alpha amino acid group Chemical group 0.000 description 6
- 150000001413 amino acids Chemical class 0.000 description 6
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 235000012000 cholesterol Nutrition 0.000 description 6
- 208000035475 disorder Diseases 0.000 description 6
- 210000000871 endothelium corneal Anatomy 0.000 description 6
- 230000006870 function Effects 0.000 description 6
- 230000002068 genetic effect Effects 0.000 description 6
- 239000002777 nucleoside Substances 0.000 description 6
- 229910052760 oxygen Inorganic materials 0.000 description 6
- 239000001301 oxygen Substances 0.000 description 6
- 238000004806 packaging method and process Methods 0.000 description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 6
- 230000002441 reversible effect Effects 0.000 description 6
- 231100000331 toxic Toxicity 0.000 description 6
- 230000002588 toxic effect Effects 0.000 description 6
- 230000003612 virological effect Effects 0.000 description 6
- 239000013607 AAV vector Substances 0.000 description 5
- HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 description 5
- JZNWSCPGTDBMEW-UHFFFAOYSA-N Glycerophosphorylethanolamin Natural products NCCOP(O)(=O)OCC(O)CO JZNWSCPGTDBMEW-UHFFFAOYSA-N 0.000 description 5
- PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 5
- 241000700584 Simplexvirus Species 0.000 description 5
- HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 description 5
- 210000000399 corneal endothelial cell Anatomy 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- GZQKNULLWNGMCW-PWQABINMSA-N lipid A (E. coli) Chemical compound O1[C@H](CO)[C@@H](OP(O)(O)=O)[C@H](OC(=O)C[C@@H](CCCCCCCCCCC)OC(=O)CCCCCCCCCCCCC)[C@@H](NC(=O)C[C@@H](CCCCCCCCCCC)OC(=O)CCCCCCCCCCC)[C@@H]1OC[C@@H]1[C@@H](O)[C@H](OC(=O)C[C@H](O)CCCCCCCCCCC)[C@@H](NC(=O)C[C@H](O)CCCCCCCCCCC)[C@@H](OP(O)(O)=O)O1 GZQKNULLWNGMCW-PWQABINMSA-N 0.000 description 5
- 230000001404 mediated effect Effects 0.000 description 5
- 239000002245 particle Substances 0.000 description 5
- 108090000765 processed proteins & peptides Proteins 0.000 description 5
- 230000008439 repair process Effects 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 241000894007 species Species 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 229940124597 therapeutic agent Drugs 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- 241000701161 unidentified adenovirus Species 0.000 description 5
- 238000011144 upstream manufacturing Methods 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- 108091034117 Oligonucleotide Proteins 0.000 description 4
- 229910019142 PO4 Inorganic materials 0.000 description 4
- 125000003118 aryl group Chemical group 0.000 description 4
- 125000004429 atom Chemical group 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- 125000005647 linker group Chemical group 0.000 description 4
- 230000007246 mechanism Effects 0.000 description 4
- 235000021317 phosphate Nutrition 0.000 description 4
- 102000040430 polynucleotide Human genes 0.000 description 4
- 108091033319 polynucleotide Proteins 0.000 description 4
- 239000002157 polynucleotide Substances 0.000 description 4
- 238000012163 sequencing technique Methods 0.000 description 4
- 238000001890 transfection Methods 0.000 description 4
- CITHEXJVPOWHKC-UUWRZZSWSA-N 1,2-di-O-myristoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCCCC CITHEXJVPOWHKC-UUWRZZSWSA-N 0.000 description 3
- BBGNINPPDHJETF-UHFFFAOYSA-N 5-heptadecylresorcinol Chemical compound CCCCCCCCCCCCCCCCCC1=CC(O)=CC(O)=C1 BBGNINPPDHJETF-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 108091093088 Amplicon Proteins 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- 241000701533 Escherichia virus T4 Species 0.000 description 3
- 108700024394 Exon Proteins 0.000 description 3
- 208000003923 Hereditary Corneal Dystrophies Diseases 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- 238000012300 Sequence Analysis Methods 0.000 description 3
- 241000191967 Staphylococcus aureus Species 0.000 description 3
- 241000194017 Streptococcus Species 0.000 description 3
- RYYWUUFWQRZTIU-UHFFFAOYSA-N Thiophosphoric acid Chemical group OP(O)(S)=O RYYWUUFWQRZTIU-UHFFFAOYSA-N 0.000 description 3
- 108091036066 Three prime untranslated region Proteins 0.000 description 3
- 108091028113 Trans-activating crRNA Proteins 0.000 description 3
- 125000003282 alkyl amino group Chemical group 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
- 125000001769 aryl amino group Chemical group 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 230000030833 cell death Effects 0.000 description 3
- 238000010367 cloning Methods 0.000 description 3
- 238000002648 combination therapy Methods 0.000 description 3
- 206010011005 corneal dystrophy Diseases 0.000 description 3
- 125000000753 cycloalkyl group Chemical group 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- 230000008021 deposition Effects 0.000 description 3
- 125000004663 dialkyl amino group Chemical group 0.000 description 3
- 125000004986 diarylamino group Chemical group 0.000 description 3
- 229960003724 dimyristoylphosphatidylcholine Drugs 0.000 description 3
- 239000006196 drop Substances 0.000 description 3
- 210000002889 endothelial cell Anatomy 0.000 description 3
- 210000003527 eukaryotic cell Anatomy 0.000 description 3
- 229940012356 eye drops Drugs 0.000 description 3
- 125000005843 halogen group Chemical group 0.000 description 3
- 125000005241 heteroarylamino group Chemical group 0.000 description 3
- 125000000623 heterocyclic group Chemical group 0.000 description 3
- 230000000977 initiatory effect Effects 0.000 description 3
- 230000010354 integration Effects 0.000 description 3
- 239000010410 layer Substances 0.000 description 3
- 210000001232 limbus corneae Anatomy 0.000 description 3
- 239000002502 liposome Substances 0.000 description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 3
- 150000003833 nucleoside derivatives Chemical class 0.000 description 3
- 239000010452 phosphate Substances 0.000 description 3
- 150000003904 phospholipids Chemical class 0.000 description 3
- 229910052698 phosphorus Inorganic materials 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- 102000004196 processed proteins & peptides Human genes 0.000 description 3
- 238000002271 resection Methods 0.000 description 3
- 230000005783 single-strand break Effects 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 150000003431 steroids Chemical class 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- 125000000547 substituted alkyl group Chemical group 0.000 description 3
- 230000002103 transcriptional effect Effects 0.000 description 3
- 210000000605 viral structure Anatomy 0.000 description 3
- 230000004304 visual acuity Effects 0.000 description 3
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 2
- KILNVBDSWZSGLL-KXQOOQHDSA-N 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCCCCCC KILNVBDSWZSGLL-KXQOOQHDSA-N 0.000 description 2
- PZNPLUBHRSSFHT-RRHRGVEJSA-N 1-hexadecanoyl-2-octadecanoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[C@@H](COP([O-])(=O)OCC[N+](C)(C)C)COC(=O)CCCCCCCCCCCCCCC PZNPLUBHRSSFHT-RRHRGVEJSA-N 0.000 description 2
- 101710169336 5'-deoxyadenosine deaminase Proteins 0.000 description 2
- LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical compound O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 description 2
- 102000055025 Adenosine deaminases Human genes 0.000 description 2
- 241000193830 Bacillus <bacterium> Species 0.000 description 2
- 241000589875 Campylobacter jejuni Species 0.000 description 2
- 108091026890 Coding region Proteins 0.000 description 2
- 102100024337 Collagen alpha-1(VIII) chain Human genes 0.000 description 2
- 230000033616 DNA repair Effects 0.000 description 2
- 206010061818 Disease progression Diseases 0.000 description 2
- 108010042407 Endonucleases Proteins 0.000 description 2
- 102000004533 Endonucleases Human genes 0.000 description 2
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 2
- 101000909492 Homo sapiens Collagen alpha-1(VIII) chain Proteins 0.000 description 2
- 241000186660 Lactobacillus Species 0.000 description 2
- 241000186869 Lactobacillus salivarius Species 0.000 description 2
- 241000713666 Lentivirus Species 0.000 description 2
- 239000012098 Lipofectamine RNAiMAX Substances 0.000 description 2
- 241000919925 Nitrosococcus halophilus Species 0.000 description 2
- 241000059630 Nodularia <Cyanobacteria> Species 0.000 description 2
- WSDRAZIPGVLSNP-UHFFFAOYSA-N O.P(=O)(O)(O)O.O.O.P(=O)(O)(O)O Chemical compound O.P(=O)(O)(O)O.O.O.P(=O)(O)(O)O WSDRAZIPGVLSNP-UHFFFAOYSA-N 0.000 description 2
- 241000606860 Pasteurella Species 0.000 description 2
- 108091093037 Peptide nucleic acid Proteins 0.000 description 2
- 102000011755 Phosphoglycerate Kinase Human genes 0.000 description 2
- 241000190967 Rhodospirillum Species 0.000 description 2
- 241000714474 Rous sarcoma virus Species 0.000 description 2
- 102100022433 Single-stranded DNA cytosine deaminase Human genes 0.000 description 2
- 101710143275 Single-stranded DNA cytosine deaminase Proteins 0.000 description 2
- 241000194020 Streptococcus thermophilus Species 0.000 description 2
- 241000187191 Streptomyces viridochromogenes Species 0.000 description 2
- 108091027544 Subgenomic mRNA Proteins 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- 101001099217 Thermotoga maritima (strain ATCC 43589 / DSM 3109 / JCM 10099 / NBRC 100826 / MSB8) Triosephosphate isomerase Proteins 0.000 description 2
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 2
- 241000589886 Treponema Species 0.000 description 2
- 108091023045 Untranslated Region 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
- 238000009825 accumulation Methods 0.000 description 2
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 2
- 230000002776 aggregation Effects 0.000 description 2
- 238000004220 aggregation Methods 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- 125000003710 aryl alkyl group Chemical group 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 230000003915 cell function Effects 0.000 description 2
- 230000001186 cumulative effect Effects 0.000 description 2
- 125000004093 cyano group Chemical group *C#N 0.000 description 2
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 150000001985 dialkylglycerols Chemical class 0.000 description 2
- 125000005240 diheteroarylamino group Chemical group 0.000 description 2
- 230000005750 disease progression Effects 0.000 description 2
- 235000013399 edible fruits Nutrition 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 230000009395 genetic defect Effects 0.000 description 2
- 238000010362 genome editing Methods 0.000 description 2
- 125000001072 heteroaryl group Chemical group 0.000 description 2
- 210000005260 human cell Anatomy 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 230000028993 immune response Effects 0.000 description 2
- 229960003444 immunosuppressant agent Drugs 0.000 description 2
- 230000001861 immunosuppressant effect Effects 0.000 description 2
- 239000003018 immunosuppressive agent Substances 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 230000015788 innate immune response Effects 0.000 description 2
- 229940039696 lactobacillus Drugs 0.000 description 2
- 210000004962 mammalian cell Anatomy 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 150000002739 metals Chemical class 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 239000000693 micelle Substances 0.000 description 2
- 230000003228 microsomal effect Effects 0.000 description 2
- 229940102129 muro 128 Drugs 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 125000001312 palmitoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 150000008104 phosphatidylethanolamines Chemical class 0.000 description 2
- 150000004713 phosphodiesters Chemical group 0.000 description 2
- 125000004437 phosphorous atom Chemical group 0.000 description 2
- 239000013612 plasmid Substances 0.000 description 2
- 238000006116 polymerization reaction Methods 0.000 description 2
- 230000000750 progressive effect Effects 0.000 description 2
- 150000003212 purines Chemical class 0.000 description 2
- 150000003230 pyrimidines Chemical class 0.000 description 2
- 230000010076 replication Effects 0.000 description 2
- GHMLBKRAJCXXBS-UHFFFAOYSA-N resorcinol Chemical compound OC1=CC=CC(O)=C1 GHMLBKRAJCXXBS-UHFFFAOYSA-N 0.000 description 2
- 230000001177 retroviral effect Effects 0.000 description 2
- 201000000980 schizophrenia Diseases 0.000 description 2
- 230000035939 shock Effects 0.000 description 2
- 238000004904 shortening Methods 0.000 description 2
- 150000008163 sugars Chemical class 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 239000011593 sulfur Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000011191 terminal modification Methods 0.000 description 2
- 238000010361 transduction Methods 0.000 description 2
- 230000026683 transduction Effects 0.000 description 2
- 238000013519 translation Methods 0.000 description 2
- 230000014616 translation Effects 0.000 description 2
- 241000701447 unidentified baculovirus Species 0.000 description 2
- NEZDNQCXEZDCBI-WJOKGBTCSA-N (2-aminoethoxy)[(2r)-2,3-bis(tetradecanoyloxy)propoxy]phosphinic acid Chemical compound CCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OCCN)OC(=O)CCCCCCCCCCCCC NEZDNQCXEZDCBI-WJOKGBTCSA-N 0.000 description 1
- YKIOPDIXYAUOFN-YACUFSJGSA-N (2-{[(2r)-2,3-bis(icosanoyloxy)propyl phosphonato]oxy}ethyl)trimethylazanium Chemical compound CCCCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCCCCCCCCCC YKIOPDIXYAUOFN-YACUFSJGSA-N 0.000 description 1
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 description 1
- 125000006716 (C1-C6) heteroalkyl group Chemical group 0.000 description 1
- FVXDQWZBHIXIEJ-LNDKUQBDSA-N 1,2-di-[(9Z,12Z)-octadecadienoyl]-sn-glycero-3-phosphocholine Chemical compound CCCCC\C=C/C\C=C/CCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C/C\C=C/CCCCC FVXDQWZBHIXIEJ-LNDKUQBDSA-N 0.000 description 1
- 229940083937 1,2-diarachidoyl-sn-glycero-3-phosphocholine Drugs 0.000 description 1
- UHDGCWIWMRVCDJ-UHFFFAOYSA-N 1-beta-D-Xylofuranosyl-NH-Cytosine Natural products O=C1N=C(N)C=CN1C1C(O)C(O)C(CO)O1 UHDGCWIWMRVCDJ-UHFFFAOYSA-N 0.000 description 1
- ASWBNKHCZGQVJV-HSZRJFAPSA-N 1-hexadecanoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@@H](O)COP([O-])(=O)OCC[N+](C)(C)C ASWBNKHCZGQVJV-HSZRJFAPSA-N 0.000 description 1
- RFVFQQWKPSOBED-PSXMRANNSA-N 1-myristoyl-2-palmitoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)O[C@@H](COP([O-])(=O)OCC[N+](C)(C)C)COC(=O)CCCCCCCCCCCCC RFVFQQWKPSOBED-PSXMRANNSA-N 0.000 description 1
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 1
- ASJSAQIRZKANQN-CRCLSJGQSA-N 2-deoxy-D-ribose Chemical compound OC[C@@H](O)[C@@H](O)CC=O ASJSAQIRZKANQN-CRCLSJGQSA-N 0.000 description 1
- FZIIBDOXPQOKBP-UHFFFAOYSA-N 2-methyloxetane Chemical group CC1CCO1 FZIIBDOXPQOKBP-UHFFFAOYSA-N 0.000 description 1
- 108020005345 3' Untranslated Regions Proteins 0.000 description 1
- 108020003589 5' Untranslated Regions Proteins 0.000 description 1
- 102000012758 APOBEC-1 Deaminase Human genes 0.000 description 1
- 108010079649 APOBEC-1 Deaminase Proteins 0.000 description 1
- 241000007910 Acaryochloris marina Species 0.000 description 1
- 241001135192 Acetohalobium arabaticum Species 0.000 description 1
- 241000604451 Acidaminococcus Species 0.000 description 1
- 241001464929 Acidithiobacillus caldus Species 0.000 description 1
- 241000605222 Acidithiobacillus ferrooxidans Species 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 241000640374 Alicyclobacillus acidocaldarius Species 0.000 description 1
- 229930188104 Alkylresorcinol Natural products 0.000 description 1
- 241000190857 Allochromatium vinosum Species 0.000 description 1
- 241000147155 Ammonifex degensii Species 0.000 description 1
- 101100114364 Arabidopsis thaliana COL8 gene Proteins 0.000 description 1
- 241001495180 Arthrospira Species 0.000 description 1
- 241000620196 Arthrospira maxima Species 0.000 description 1
- 240000002900 Arthrospira platensis Species 0.000 description 1
- 235000016425 Arthrospira platensis Nutrition 0.000 description 1
- 206010003571 Astrocytoma Diseases 0.000 description 1
- 241000193738 Bacillus anthracis Species 0.000 description 1
- 241000906059 Bacillus pseudomycoides Species 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 108091032955 Bacterial small RNA Proteins 0.000 description 1
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 241000823281 Burkholderiales bacterium Species 0.000 description 1
- 241000219357 Cactaceae Species 0.000 description 1
- 101100455752 Caenorhabditis elegans lys-3 gene Proteins 0.000 description 1
- 241000589986 Campylobacter lari Species 0.000 description 1
- 241001496650 Candidatus Desulforudis Species 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 208000002177 Cataract Diseases 0.000 description 1
- 108020004638 Circular DNA Proteins 0.000 description 1
- 108091028075 Circular RNA Proteins 0.000 description 1
- 241000193163 Clostridioides difficile Species 0.000 description 1
- 241000193155 Clostridium botulinum Species 0.000 description 1
- 102100040496 Collagen alpha-2(VIII) chain Human genes 0.000 description 1
- 241000186216 Corynebacterium Species 0.000 description 1
- 241000065716 Crocosphaera watsonii Species 0.000 description 1
- 241000159506 Cyanothece Species 0.000 description 1
- UHDGCWIWMRVCDJ-PSQAKQOGSA-N Cytidine Natural products O=C1N=C(N)C=CN1[C@@H]1[C@@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-PSQAKQOGSA-N 0.000 description 1
- 108010031325 Cytidine deaminase Proteins 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 241000701022 Cytomegalovirus Species 0.000 description 1
- 102220605874 Cytosolic arginine sensor for mTORC1 subunit 2_D10A_mutation Human genes 0.000 description 1
- 238000007400 DNA extraction Methods 0.000 description 1
- 241000702421 Dependoparvovirus Species 0.000 description 1
- 101100118093 Drosophila melanogaster eEF1alpha2 gene Proteins 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
- 241000326311 Exiguobacterium sibiricum Species 0.000 description 1
- 241000605896 Fibrobacter succinogenes Species 0.000 description 1
- 241000192016 Finegoldia magna Species 0.000 description 1
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 1
- 241000589599 Francisella tularensis subsp. novicida Species 0.000 description 1
- 241000968725 Gammaproteobacteria bacterium Species 0.000 description 1
- 206010064571 Gene mutation Diseases 0.000 description 1
- 208000010412 Glaucoma Diseases 0.000 description 1
- 108010044091 Globulins Proteins 0.000 description 1
- 102000006395 Globulins Human genes 0.000 description 1
- 108010012029 Guanine Deaminase Proteins 0.000 description 1
- 102000013587 Guanine deaminase Human genes 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 101000749886 Homo sapiens Collagen alpha-2(VIII) chain Proteins 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 208000026350 Inborn Genetic disease Diseases 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 108010050904 Interferons Proteins 0.000 description 1
- 108091092195 Intron Proteins 0.000 description 1
- 241001430080 Ktedonobacter racemifer Species 0.000 description 1
- 241000689670 Lachnospiraceae bacterium ND2006 Species 0.000 description 1
- 241000186679 Lactobacillus buchneri Species 0.000 description 1
- 241000186673 Lactobacillus delbrueckii Species 0.000 description 1
- 241000186606 Lactobacillus gasseri Species 0.000 description 1
- 108091026898 Leader sequence (mRNA) Proteins 0.000 description 1
- 239000000232 Lipid Bilayer Substances 0.000 description 1
- 241000186781 Listeria Species 0.000 description 1
- 241000186805 Listeria innocua Species 0.000 description 1
- 241001134698 Lyngbya Species 0.000 description 1
- 241000206589 Marinobacter Species 0.000 description 1
- 101710085938 Matrix protein Proteins 0.000 description 1
- 101710127721 Membrane protein Proteins 0.000 description 1
- 102100030550 Menin Human genes 0.000 description 1
- 101710169972 Menin Proteins 0.000 description 1
- 201000009906 Meningitis Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241000204637 Methanohalobium evestigatum Species 0.000 description 1
- 241000179981 Microcoleus sp. Species 0.000 description 1
- 241000192710 Microcystis aeruginosa Species 0.000 description 1
- 108091092878 Microsatellite Proteins 0.000 description 1
- 241000190928 Microscilla marina Species 0.000 description 1
- 241000713333 Mouse mammary tumor virus Species 0.000 description 1
- 241000167285 Natranaerobius thermophilus Species 0.000 description 1
- 241000588654 Neisseria cinerea Species 0.000 description 1
- 241000588650 Neisseria meningitidis Species 0.000 description 1
- 241001515112 Nitrosococcus watsonii Species 0.000 description 1
- 241000203619 Nocardiopsis dassonvillei Species 0.000 description 1
- 108020004485 Nonsense Codon Proteins 0.000 description 1
- 241000192673 Nostoc sp. Species 0.000 description 1
- TTZMPOZCBFTTPR-UHFFFAOYSA-N O=P1OCO1 Chemical compound O=P1OCO1 TTZMPOZCBFTTPR-UHFFFAOYSA-N 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 241000192497 Oscillatoria Species 0.000 description 1
- 241001386755 Parvibaculum lavamentivorans Species 0.000 description 1
- 241001425545 Pelotomaculum Species 0.000 description 1
- 241001135648 Petrotoga Species 0.000 description 1
- 241000983938 Petrotoga mobilis Species 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 101000931422 Photobacterium phosphoreum Methenyltetrahydrofolate cyclohydrolase Proteins 0.000 description 1
- 241000512220 Polaromonas Species 0.000 description 1
- 241001472610 Polaromonas sp. Species 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 229920002396 Polyurea Polymers 0.000 description 1
- 206010036790 Productive cough Diseases 0.000 description 1
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 1
- 241000519590 Pseudoalteromonas Species 0.000 description 1
- 241000590028 Pseudoalteromonas haloplanktis Species 0.000 description 1
- 241000589516 Pseudomonas Species 0.000 description 1
- 101000998536 Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1) Proteinase inhibitor Proteins 0.000 description 1
- 102000014450 RNA Polymerase III Human genes 0.000 description 1
- 108010078067 RNA Polymerase III Proteins 0.000 description 1
- 102000015097 RNA Splicing Factors Human genes 0.000 description 1
- 108010039259 RNA Splicing Factors Proteins 0.000 description 1
- 230000007022 RNA scission Effects 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 101000752546 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) Transaminated amino acid decarboxylase Proteins 0.000 description 1
- 108020004682 Single-Stranded DNA Proteins 0.000 description 1
- 241001147693 Staphylococcus sp. Species 0.000 description 1
- 229930182558 Sterol Natural products 0.000 description 1
- 241001501869 Streptococcus pasteurianus Species 0.000 description 1
- 241000193996 Streptococcus pyogenes Species 0.000 description 1
- 241000194022 Streptococcus sp. Species 0.000 description 1
- 241000187747 Streptomyces Species 0.000 description 1
- 241001518258 Streptomyces pristinaespiralis Species 0.000 description 1
- 241000203590 Streptosporangium Species 0.000 description 1
- 241000123713 Sutterella wadsworthensis Species 0.000 description 1
- 241000192707 Synechococcus Species 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 241000078013 Trichormus variabilis Species 0.000 description 1
- 102000004243 Tubulin Human genes 0.000 description 1
- 108090000704 Tubulin Proteins 0.000 description 1
- 108090000848 Ubiquitin Proteins 0.000 description 1
- 102000044159 Ubiquitin Human genes 0.000 description 1
- 101150047749 VIII gene Proteins 0.000 description 1
- 108700005077 Viral Genes Proteins 0.000 description 1
- 108010067390 Viral Proteins Proteins 0.000 description 1
- 241000282485 Vulpes vulpes Species 0.000 description 1
- CWRILEGKIAOYKP-SSDOTTSWSA-M [(2r)-3-acetyloxy-2-hydroxypropyl] 2-aminoethyl phosphate Chemical compound CC(=O)OC[C@@H](O)COP([O-])(=O)OCCN CWRILEGKIAOYKP-SSDOTTSWSA-M 0.000 description 1
- 241001673106 [Bacillus] selenitireducens Species 0.000 description 1
- 230000007488 abnormal function Effects 0.000 description 1
- 150000001241 acetals Chemical class 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 239000010441 alabaster Substances 0.000 description 1
- PPQRONHOSHZGFQ-LMVFSUKVSA-N aldehydo-D-ribose 5-phosphate Chemical group OP(=O)(O)OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PPQRONHOSHZGFQ-LMVFSUKVSA-N 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 125000006350 alkyl thio alkyl group Chemical group 0.000 description 1
- 125000000304 alkynyl group Chemical group 0.000 description 1
- 125000002431 aminoalkoxy group Chemical group 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 230000000692 anti-sense effect Effects 0.000 description 1
- PYMYPHUHKUWMLA-WDCZJNDASA-N arabinose Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)C=O PYMYPHUHKUWMLA-WDCZJNDASA-N 0.000 description 1
- PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 1
- 229940011019 arthrospira platensis Drugs 0.000 description 1
- 210000004507 artificial chromosome Anatomy 0.000 description 1
- 125000004104 aryloxy group Chemical group 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 1
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 1
- 125000001369 canonical nucleoside group Chemical group 0.000 description 1
- 210000000234 capsid Anatomy 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 150000003857 carboxamides Chemical class 0.000 description 1
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 230000006727 cell loss Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000036755 cellular response Effects 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- WLNARFZDISHUGS-MIXBDBMTSA-N cholesteryl hemisuccinate Chemical compound C1C=C2C[C@@H](OC(=O)CCC(O)=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 WLNARFZDISHUGS-MIXBDBMTSA-N 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- MYSWGUAQZAJSOK-UHFFFAOYSA-N ciprofloxacin Chemical compound C12=CC(N3CCNCC3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 MYSWGUAQZAJSOK-UHFFFAOYSA-N 0.000 description 1
- 238000003759 clinical diagnosis Methods 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 238000005520 cutting process Methods 0.000 description 1
- UHDGCWIWMRVCDJ-ZAKLUEHWSA-N cytidine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-ZAKLUEHWSA-N 0.000 description 1
- 229940104302 cytosine Drugs 0.000 description 1
- 238000006481 deamination reaction Methods 0.000 description 1
- GHVNFZFCNZKVNT-UHFFFAOYSA-N decanoic acid Chemical compound CCCCCCCCCC(O)=O GHVNFZFCNZKVNT-UHFFFAOYSA-N 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 150000001982 diacylglycerols Chemical class 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 206010013023 diphtheria Diseases 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 230000008497 endothelial barrier function Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 210000001808 exosome Anatomy 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 239000003885 eye ointment Substances 0.000 description 1
- 230000004720 fertilization Effects 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 230000037433 frameshift Effects 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 238000012239 gene modification Methods 0.000 description 1
- 208000016361 genetic disease Diseases 0.000 description 1
- 230000005017 genetic modification Effects 0.000 description 1
- 235000013617 genetically modified food Nutrition 0.000 description 1
- 239000003862 glucocorticoid Substances 0.000 description 1
- PEDCQBHIVMGVHV-UHFFFAOYSA-N glycerol Substances OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 210000003128 head Anatomy 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 238000000126 in silico method Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 239000008384 inner phase Substances 0.000 description 1
- 238000009830 intercalation Methods 0.000 description 1
- 229940047124 interferons Drugs 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 206010023365 keratopathy Diseases 0.000 description 1
- 239000002479 lipoplex Substances 0.000 description 1
- 238000013507 mapping Methods 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000034217 membrane fusion Effects 0.000 description 1
- YACKEPLHDIMKIO-UHFFFAOYSA-N methylphosphonic acid Chemical compound CP(O)(O)=O YACKEPLHDIMKIO-UHFFFAOYSA-N 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 229940042880 natural phospholipid Drugs 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- OYHQOLUKZRVURQ-UHFFFAOYSA-M octadeca-9,12-dienoate Chemical compound CCCCCC=CCC=CCCCCCCCC([O-])=O OYHQOLUKZRVURQ-UHFFFAOYSA-M 0.000 description 1
- 230000009437 off-target effect Effects 0.000 description 1
- 229940069265 ophthalmic ointment Drugs 0.000 description 1
- 239000002997 ophthalmic solution Substances 0.000 description 1
- 229940054534 ophthalmic solution Drugs 0.000 description 1
- 230000002611 ovarian Effects 0.000 description 1
- 150000002923 oximes Chemical class 0.000 description 1
- 210000004738 parenchymal cell Anatomy 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 1
- PTMHPRAIXMAOOB-UHFFFAOYSA-L phosphoramidate Chemical compound NP([O-])([O-])=O PTMHPRAIXMAOOB-UHFFFAOYSA-L 0.000 description 1
- PTMHPRAIXMAOOB-UHFFFAOYSA-N phosphoramidic acid Chemical class NP(O)(O)=O PTMHPRAIXMAOOB-UHFFFAOYSA-N 0.000 description 1
- 150000003014 phosphoric acid esters Chemical class 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229920000765 poly(2-oxazolines) Polymers 0.000 description 1
- 229920001308 poly(aminoacid) Polymers 0.000 description 1
- 229920002946 poly[2-(methacryloxy)ethyl phosphorylcholine] polymer Polymers 0.000 description 1
- 229920002187 poly[N-2-(hydroxypropyl) methacrylamide] polymer Polymers 0.000 description 1
- 229920001281 polyalkylene Polymers 0.000 description 1
- 229920000223 polyglycerol Polymers 0.000 description 1
- 102000054765 polymorphisms of proteins Human genes 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000002250 progressing effect Effects 0.000 description 1
- 210000001236 prokaryotic cell Anatomy 0.000 description 1
- JIFDAPBDLWBOGR-UHFFFAOYSA-N propane-1,2,3-triol;pyrrolidin-2-one Chemical compound OCC(O)CO.O=C1CCCN1 JIFDAPBDLWBOGR-UHFFFAOYSA-N 0.000 description 1
- AJAMRCUNWLZBDF-UHFFFAOYSA-N propyl octadeca-9,12-dienoate Chemical compound CCCCCC=CCC=CCCCCCCCC(=O)OCCC AJAMRCUNWLZBDF-UHFFFAOYSA-N 0.000 description 1
- 230000009103 reabsorption Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000011514 reflex Effects 0.000 description 1
- 230000003252 repetitive effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 125000000548 ribosyl group Chemical group C1([C@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- JRPHGDYSKGJTKZ-UHFFFAOYSA-N selenophosphoric acid Chemical class OP(O)([SeH])=O JRPHGDYSKGJTKZ-UHFFFAOYSA-N 0.000 description 1
- UQDJGEHQDNVPGU-UHFFFAOYSA-N serine phosphoethanolamine Chemical compound [NH3+]CCOP([O-])(=O)OCC([NH3+])C([O-])=O UQDJGEHQDNVPGU-UHFFFAOYSA-N 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- 125000006850 spacer group Chemical group 0.000 description 1
- 208000024794 sputum Diseases 0.000 description 1
- 210000003802 sputum Anatomy 0.000 description 1
- 150000003432 sterols Chemical class 0.000 description 1
- 235000003702 sterols Nutrition 0.000 description 1
- 210000000352 storage cell Anatomy 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000005309 thioalkoxy group Chemical group 0.000 description 1
- 150000003568 thioethers Chemical class 0.000 description 1
- 125000003396 thiol group Chemical class [H]S* 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 230000004393 visual impairment Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 229940075420 xanthine Drugs 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
- A61K31/7105—Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
- A61K48/005—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered
- A61K48/0066—Manipulation of the nucleic acid to modify its expression pattern, e.g. enhance its duration of expression, achieved by the presence of particular introns in the delivered nucleic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/465—Hydrolases (3) acting on ester bonds (3.1), e.g. lipases, ribonucleases
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
- A61K48/005—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered
- A61K48/0058—Nucleic acids adapted for tissue specific expression, e.g. having tissue specific promoters as part of a contruct
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
- A61K48/0075—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the delivery route, e.g. oral, subcutaneous
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0048—Eye, e.g. artificial tears
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0048—Eye, e.g. artificial tears
- A61K9/0051—Ocular inserts, ocular implants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5107—Excipients; Inactive ingredients
- A61K9/5176—Compounds of unknown constitution, e.g. material from plants or animals
- A61K9/5184—Virus capsids or envelopes enclosing drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- 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
- 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
- C12N15/102—Mutagenizing nucleic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5107—Excipients; Inactive ingredients
- A61K9/5176—Compounds of unknown constitution, e.g. material from plants or animals
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/10—Type of nucleic acid
- C12N2310/20—Type of nucleic acid involving clustered regularly interspaced short palindromic repeats [CRISPR]
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Biomedical Technology (AREA)
- Organic Chemistry (AREA)
- Biotechnology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Zoology (AREA)
- Biochemistry (AREA)
- Ophthalmology & Optometry (AREA)
- Biophysics (AREA)
- Physics & Mathematics (AREA)
- General Engineering & Computer Science (AREA)
- Wood Science & Technology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Virology (AREA)
- Gastroenterology & Hepatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Nanotechnology (AREA)
- Immunology (AREA)
- Optics & Photonics (AREA)
- Botany (AREA)
- Psychology (AREA)
- Microbiology (AREA)
- Plant Pathology (AREA)
- Crystallography & Structural Chemistry (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201662326700P | 2016-04-22 | 2016-04-22 | |
| US62/326,700 | 2016-04-22 | ||
| PCT/US2017/028981 WO2017185054A1 (en) | 2016-04-22 | 2017-04-21 | Compositions and methods for treatment of diseases associated with trinucleotide repeats in transcription factor four |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20180134412A true KR20180134412A (ko) | 2018-12-18 |
Family
ID=58692575
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020187033525A Ceased KR20180134412A (ko) | 2016-04-22 | 2017-04-21 | 전사 인자 4에서 트라이뉴클레오타이드 반복부와 연관된 질환의 치료를 위한 조성물 및 방법 |
Country Status (11)
| Country | Link |
|---|---|
| US (2) | US20190142972A1 (enExample) |
| EP (1) | EP3445375A1 (enExample) |
| JP (1) | JP2019515914A (enExample) |
| KR (1) | KR20180134412A (enExample) |
| CN (1) | CN109414450A (enExample) |
| AU (1) | AU2017254718A1 (enExample) |
| BR (1) | BR112018071439A2 (enExample) |
| CA (1) | CA3021647A1 (enExample) |
| CO (1) | CO2018012433A2 (enExample) |
| MX (1) | MX2018012873A (enExample) |
| WO (1) | WO2017185054A1 (enExample) |
Families Citing this family (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BR112017028201A2 (pt) * | 2015-07-02 | 2018-08-28 | Univ Johns Hopkins | tratamentos com base em crisp/cas9 |
| WO2022072458A1 (en) * | 2020-09-29 | 2022-04-07 | Avellino Lab Usa, Inc. | Crispr/cas9 targeted excision of the intronic ctg18.1 trinucleotide repeat expansion of tcf4 as a therapy in fuchs' endothelial corneal dystrophy |
| BR112019012825A2 (pt) | 2016-12-22 | 2019-11-26 | Intellia Therapeutics Inc | composições e métodos para tratar deficiência de alfa-1 antitripsina |
| US11512312B2 (en) | 2017-03-10 | 2022-11-29 | The Board Of Regents Of The University Of Texas System | Treatment of Fuchs' endothelial corneal dystrophy |
| US20230201373A1 (en) * | 2017-12-15 | 2023-06-29 | Regents Of The University Of Minnesota | Crispr-mediated genome editing with vectors |
| CN109929872A (zh) * | 2017-12-18 | 2019-06-25 | 中国科学院遗传与发育生物学研究所 | 一种通过基因编辑技术创制番茄白果材料的方法 |
| EP3728598A1 (en) * | 2017-12-21 | 2020-10-28 | Max-Delbrück-Centrum für Molekulare Medizin in der Helmholtz-Gemeinschaft | Nucleic acid sequence replacement by nhej |
| US20190151470A1 (en) * | 2018-01-21 | 2019-05-23 | RoverMed BioSciences, LLC | Nanoparticles comprising protein-polynucleotide complexes and for delivering protein based complexes |
| TW202045186A (zh) * | 2019-02-28 | 2020-12-16 | 弗里德里希 Ｅ 克魯斯 | 細胞外基質調節劑 |
| EP3930694A1 (en) * | 2019-02-28 | 2022-01-05 | Regeneron Pharmaceuticals, Inc. | Adeno-associated virus vectors for the delivery of therapeutics |
| US20230349888A1 (en) * | 2020-04-27 | 2023-11-02 | Duke University | A high-throughput screening method to discover optimal grna pairs for crispr-mediated exon deletion |
| CN111944814B (zh) * | 2020-08-24 | 2022-07-15 | 武汉纽福斯生物科技有限公司 | 寡核苷酸、病毒载体及其应用和RNAi药物制剂 |
| CN111944813B (zh) * | 2020-08-24 | 2022-07-15 | 武汉纽福斯生物科技有限公司 | 核苷酸、病毒载体及其应用和RNAi药物制剂 |
| JP2023553935A (ja) | 2020-12-11 | 2023-12-26 | インテリア セラピューティクス，インコーポレイテッド | 脱アミノ化を伴うゲノム編集のためのポリヌクレオチド、組成物、及び方法 |
| EP4288541A1 (en) | 2021-02-05 | 2023-12-13 | Christiana Care Gene Editing Institute, Inc. | Methods of and compositions for reducing gene expression and/or activity |
| US20250319202A1 (en) * | 2021-11-09 | 2025-10-16 | Prime Medicine, Inc. | Genome editing compositions and methods for treatment of fuchs endothelial corneal dystrophy |
| US12297285B2 (en) | 2022-06-24 | 2025-05-13 | Orna Therapeutics, Inc. | Circular RNA encoding chimeric antigen receptors targeting BCMA |
| WO2024226536A1 (en) * | 2023-04-24 | 2024-10-31 | The General Hospital Corporation | Methods and compositions for modifying genetic repeats |
| WO2025128871A2 (en) | 2023-12-13 | 2025-06-19 | Renagade Therapeutics Management Inc. | Lipid nanoparticles comprising coding rna molecules for use in gene editing and as vaccines and therapeutic agents |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006007712A1 (en) | 2004-07-19 | 2006-01-26 | Protiva Biotherapeutics, Inc. | Methods comprising polyethylene glycol-lipid conjugates for delivery of therapeutic agents |
| WO2013101711A1 (en) * | 2011-12-30 | 2013-07-04 | Mayo Foundation For Medical Education And Research | Assessing likelihood of developing fuchs' corneal dystrophy |
| MY189533A (en) * | 2012-05-25 | 2022-02-16 | Univ California | Methods and compositions for rna-directed target dna modification and for rna-directed modulation of transcription |
| 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 |
| WO2014136086A1 (en) | 2013-03-08 | 2014-09-12 | Novartis Ag | Lipids and lipid compositions for the delivery of active agents |
| PT3066201T (pt) * | 2013-11-07 | 2018-06-04 | Massachusetts Inst Technology | Métodos e composições relacionadas com crispr com arng reguladores |
| 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 |
| EP3083556B1 (en) | 2013-12-19 | 2019-12-25 | Novartis AG | Lipids and lipid compositions for the delivery of active agents |
| SG10201809157VA (en) * | 2014-04-18 | 2018-11-29 | Editas Medicine Inc | Crispr-cas-related methods, compositions and components for cancer immunotherapy |
| BR112017028201A2 (pt) * | 2015-07-02 | 2018-08-28 | Univ Johns Hopkins | tratamentos com base em crisp/cas9 |
-
2017
- 2017-04-21 WO PCT/US2017/028981 patent/WO2017185054A1/en not_active Ceased
- 2017-04-21 CN CN201780036135.5A patent/CN109414450A/zh active Pending
- 2017-04-21 KR KR1020187033525A patent/KR20180134412A/ko not_active Ceased
- 2017-04-21 CA CA3021647A patent/CA3021647A1/en active Pending
- 2017-04-21 US US16/095,236 patent/US20190142972A1/en not_active Abandoned
- 2017-04-21 BR BR112018071439-9A patent/BR112018071439A2/pt not_active IP Right Cessation
- 2017-04-21 JP JP2018555262A patent/JP2019515914A/ja active Pending
- 2017-04-21 MX MX2018012873A patent/MX2018012873A/es unknown
- 2017-04-21 AU AU2017254718A patent/AU2017254718A1/en not_active Abandoned
- 2017-04-21 EP EP17722552.1A patent/EP3445375A1/en not_active Withdrawn
-
2018
- 2018-11-19 CO CONC2018/0012433A patent/CO2018012433A2/es unknown
-
2024
- 2024-01-17 US US18/415,032 patent/US20250025580A1/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| CN109414450A (zh) | 2019-03-01 |
| US20190142972A1 (en) | 2019-05-16 |
| US20250025580A1 (en) | 2025-01-23 |
| WO2017185054A1 (en) | 2017-10-26 |
| AU2017254718A1 (en) | 2018-11-15 |
| BR112018071439A2 (pt) | 2019-03-19 |
| CA3021647A1 (en) | 2017-10-26 |
| MX2018012873A (es) | 2019-08-05 |
| CO2018012433A2 (es) | 2019-04-30 |
| JP2019515914A (ja) | 2019-06-13 |
| EP3445375A1 (en) | 2019-02-27 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR20180134412A (ko) | 전사 인자 4에서 트라이뉴클레오타이드 반복부와 연관된 질환의 치료를 위한 조성물 및 방법 | |
| US11332760B2 (en) | Compositions and methods for genomic editing by insertion of donor polynucleotides | |
| KR102877920B1 (ko) | 티틴-기반 근증 및 다른 티틴성병증의 치료를 위한 물질 및 방법 | |
| US20230337645A1 (en) | Nuclease-mediated repeat expansion | |
| KR20240017791A (ko) | Dna-의존적 단백질 키나제의 억제제 및 이의 조성물 및 용도 | |
| JP2022505381A (ja) | アルファ１アンチトリプシン欠乏症を治療するための組成物及び方法 | |
| CN114206108B (zh) | 包括人源化凝血因子12基因座的非人动物 | |
| KR20210096088A (ko) | 전이유전자 전달용 조성물 및 방법 | |
| US20230383275A1 (en) | Sgrna targeting aqp1 rna, and vector and use thereof | |
| KR20220097414A (ko) | X-연관 연소 망막층간분리 치료법을 위한 crispr 및 aav 전략 | |
| CA3214277A1 (en) | Ltr transposon compositions and methods | |
| TW202325848A (zh) | 用於基因體編輯之多核苷酸、組合物及方法 | |
| CA3256516A1 (en) | Compositions and methods for modulating a genome in T lymphocytes, induced pluripotent stem cells, and respiratory epithelial cells | |
| US20220389432A1 (en) | Allele-specific silencing therapy for DFNA9 using antisense oligonucleotides | |
| US20240173432A1 (en) | Compositions and Methods for Treatment of Myotonic Dystrophy Type 1 with CRISPR/SluCas9 | |
| TW202428878A (zh) | 用於基因體編輯之系統及方法 | |
| CA3202411A1 (en) | Therapeutic lama2 payload for treatment of congenital muscular dystrophy | |
| KR20220022110A (ko) | 개선된 인자 viii 발현을 사용한, a형 혈우병을 위한 유전자 편집 | |
| RU2833486C1 (ru) | Стратегии crispr и aav для терапии х-сцепленного ювенильного ретиношизиса | |
| WO2025137301A1 (en) | Methods for rapid engineering of cells | |
| JP2025542206A (ja) | ゲノム編集のためのシステムと方法 | |
| TW202408595A (zh) | 用於對細胞進行遺傳修飾之方法及組合物 | |
| HK40005344A (en) | Compositions and methods for treatment of diseases associated with trinucleotide repeats in transcription factor four | |
| EA048535B1 (ru) | Композиции и способы, содержащие гидовую рнк ttr и полинуклеотид, кодирующий днк-связывающий агент, гидируемый рнк | |
| EA043766B1 (ru) | Средства и способы лечения миопатий, связанных с титином, и других титинопатий |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PA0105 | International application |
Patent event date: 20181120 Patent event code: PA01051R01D Comment text: International Patent Application |
|
| PG1501 | Laying open of application | ||
| A201 | Request for examination | ||
| PA0201 | Request for examination |
Patent event code: PA02012R01D Patent event date: 20200421 Comment text: Request for Examination of Application |
|
| E902 | Notification of reason for refusal | ||
| PE0902 | Notice of grounds for rejection |
Comment text: Notification of reason for refusal Patent event date: 20220331 Patent event code: PE09021S01D |
|
| E601 | Decision to refuse application | ||
| PE0601 | Decision on rejection of patent |
Patent event date: 20221117 Comment text: Decision to Refuse Application Patent event code: PE06012S01D Patent event date: 20220331 Comment text: Notification of reason for refusal Patent event code: PE06011S01I |