ES2930643T3 - Seguimiento y manipulación de ARN celular a través de la administración nuclear de CRISPR/CAS9 - Google Patents
Seguimiento y manipulación de ARN celular a través de la administración nuclear de CRISPR/CAS9 Download PDFInfo
- Publication number
- ES2930643T3 ES2930643T3 ES16822766T ES16822766T ES2930643T3 ES 2930643 T3 ES2930643 T3 ES 2930643T3 ES 16822766 T ES16822766 T ES 16822766T ES 16822766 T ES16822766 T ES 16822766T ES 2930643 T3 ES2930643 T3 ES 2930643T3
- Authority
- ES
- Spain
- Prior art keywords
- rna
- rcas9
- cas9
- polypeptide
- nuclease
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 108091033409 CRISPR Proteins 0.000 title claims abstract description 253
- 108091092328 cellular RNA Proteins 0.000 title description 4
- 238000010354 CRISPR gene editing Methods 0.000 title 1
- 108091032973 (ribonucleotides)n+m Proteins 0.000 claims abstract description 387
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 180
- 102000004196 processed proteins & peptides Human genes 0.000 claims abstract description 177
- 229920001184 polypeptide Polymers 0.000 claims abstract description 165
- 238000000034 method Methods 0.000 claims abstract description 63
- 210000004027 cell Anatomy 0.000 claims description 198
- 108090000623 proteins and genes Proteins 0.000 claims description 111
- 102000004169 proteins and genes Human genes 0.000 claims description 91
- 230000008685 targeting Effects 0.000 claims description 88
- 150000007523 nucleic acids Chemical class 0.000 claims description 79
- 239000013598 vector Substances 0.000 claims description 76
- 102000039446 nucleic acids Human genes 0.000 claims description 72
- 108020004707 nucleic acids Proteins 0.000 claims description 72
- 102000011931 Nucleoproteins Human genes 0.000 claims description 51
- 108010061100 Nucleoproteins Proteins 0.000 claims description 51
- 230000014509 gene expression Effects 0.000 claims description 51
- 108020005004 Guide RNA Proteins 0.000 claims description 42
- 230000027455 binding Effects 0.000 claims description 41
- 101710163270 Nuclease Proteins 0.000 claims description 38
- 230000000694 effects Effects 0.000 claims description 38
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 34
- 201000010099 disease Diseases 0.000 claims description 33
- 239000012636 effector Substances 0.000 claims description 32
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 30
- 125000003729 nucleotide group Chemical group 0.000 claims description 28
- 108091034117 Oligonucleotide Proteins 0.000 claims description 26
- 239000002773 nucleotide Substances 0.000 claims description 24
- 102000004190 Enzymes Human genes 0.000 claims description 20
- 108090000790 Enzymes Proteins 0.000 claims description 20
- 108010077850 Nuclear Localization Signals Proteins 0.000 claims description 16
- 102000015097 RNA Splicing Factors Human genes 0.000 claims description 16
- 108010039259 RNA Splicing Factors Proteins 0.000 claims description 16
- 210000005260 human cell Anatomy 0.000 claims description 15
- 108010042407 Endonucleases Proteins 0.000 claims description 14
- 210000004962 mammalian cell Anatomy 0.000 claims description 14
- 230000004075 alteration Effects 0.000 claims description 13
- 238000011282 treatment Methods 0.000 claims description 13
- 230000000295 complement effect Effects 0.000 claims description 12
- 238000000338 in vitro Methods 0.000 claims description 11
- 239000003795 chemical substances by application Substances 0.000 claims description 10
- 239000008194 pharmaceutical composition Substances 0.000 claims description 10
- 230000002829 reductive effect Effects 0.000 claims description 10
- 102100038187 RNA binding protein fox-1 homolog 2 Human genes 0.000 claims description 9
- 230000007022 RNA scission Effects 0.000 claims description 9
- 229910052751 metal Inorganic materials 0.000 claims description 9
- 239000002184 metal Substances 0.000 claims description 9
- 108010053770 Deoxyribonucleases Proteins 0.000 claims description 8
- 102000016911 Deoxyribonucleases Human genes 0.000 claims description 8
- 230000001580 bacterial effect Effects 0.000 claims description 8
- 241000589599 Francisella tularensis subsp. novicida Species 0.000 claims description 6
- 108050008752 PIN domains Proteins 0.000 claims description 6
- 102000000309 PIN domains Human genes 0.000 claims description 6
- 230000015556 catabolic process Effects 0.000 claims description 6
- 238000006731 degradation reaction Methods 0.000 claims description 6
- 238000001990 intravenous administration Methods 0.000 claims description 6
- 238000004806 packaging method and process Methods 0.000 claims description 6
- 239000000126 substance Chemical group 0.000 claims description 6
- 230000005030 transcription termination Effects 0.000 claims description 6
- 241000702421 Dependoparvovirus Species 0.000 claims description 5
- 230000035772 mutation Effects 0.000 claims description 5
- 108010008532 Deoxyribonuclease I Proteins 0.000 claims description 4
- 102000007260 Deoxyribonuclease I Human genes 0.000 claims description 4
- 101000665452 Homo sapiens RNA binding protein fox-1 homolog 2 Proteins 0.000 claims description 4
- 108091092878 Microsatellite Proteins 0.000 claims description 4
- 208000015181 infectious disease Diseases 0.000 claims description 4
- 238000007918 intramuscular administration Methods 0.000 claims description 4
- 230000009467 reduction Effects 0.000 claims description 4
- 230000007018 DNA scission Effects 0.000 claims description 3
- 102000004533 Endonucleases Human genes 0.000 claims description 3
- 241000187479 Mycobacterium tuberculosis Species 0.000 claims description 3
- 241000191967 Staphylococcus aureus Species 0.000 claims description 3
- 208000024891 symptom Diseases 0.000 claims description 3
- 241000701161 unidentified adenovirus Species 0.000 claims description 3
- 241000589941 Azospirillum Species 0.000 claims description 2
- 241000545821 Bacteroides coprophilus Species 0.000 claims description 2
- 241000589876 Campylobacter Species 0.000 claims description 2
- 241000589986 Campylobacter lari Species 0.000 claims description 2
- 241001282092 Filifactor alocis Species 0.000 claims description 2
- 241000604777 Flavobacterium columnare Species 0.000 claims description 2
- 241001426139 Fluviicola taffensis Species 0.000 claims description 2
- 241001468096 Gluconacetobacter diazotrophicus Species 0.000 claims description 2
- 241000204991 Haloferax Species 0.000 claims description 2
- 241000186841 Lactobacillus farciminis Species 0.000 claims description 2
- 241001468157 Lactobacillus johnsonii Species 0.000 claims description 2
- 241001193656 Legionella pneumophila str. Paris Species 0.000 claims description 2
- 241000124008 Mammalia Species 0.000 claims description 2
- 241001465821 Mycoplasma gallisepticum str. F Species 0.000 claims description 2
- 241000202964 Mycoplasma mobile Species 0.000 claims description 2
- 241000588654 Neisseria cinerea Species 0.000 claims description 2
- 241000588650 Neisseria meningitidis Species 0.000 claims description 2
- 241001386755 Parvibaculum lavamentivorans Species 0.000 claims description 2
- 241000606856 Pasteurella multocida Species 0.000 claims description 2
- 241000398180 Roseburia intestinalis Species 0.000 claims description 2
- 241000044624 Sphaerochaeta globosa str. Buddy Species 0.000 claims description 2
- 241000794282 Staphylococcus pseudintermedius Species 0.000 claims description 2
- 241001501869 Streptococcus pasteurianus Species 0.000 claims description 2
- 241001633172 Streptococcus thermophilus LMD-9 Species 0.000 claims description 2
- 241000123713 Sutterella wadsworthensis Species 0.000 claims description 2
- 102100036049 T-complex protein 1 subunit gamma Human genes 0.000 claims description 2
- 241000589892 Treponema denticola Species 0.000 claims description 2
- 101150062912 cct3 gene Proteins 0.000 claims description 2
- 238000007912 intraperitoneal administration Methods 0.000 claims description 2
- 238000007911 parenteral administration Methods 0.000 claims description 2
- 229940051027 pasteurella multocida Drugs 0.000 claims description 2
- 230000002685 pulmonary effect Effects 0.000 claims description 2
- 238000007920 subcutaneous administration Methods 0.000 claims description 2
- 241000725303 Human immunodeficiency virus Species 0.000 claims 2
- 241000135933 Nitratifractor salsuginis Species 0.000 claims 1
- 241000700584 Simplexvirus Species 0.000 claims 1
- 230000002265 prevention Effects 0.000 claims 1
- 241001430294 unidentified retrovirus Species 0.000 claims 1
- 238000013519 translation Methods 0.000 abstract description 16
- 235000018102 proteins Nutrition 0.000 description 82
- 108020004999 messenger RNA Proteins 0.000 description 81
- 108020004414 DNA Proteins 0.000 description 64
- 239000000523 sample Substances 0.000 description 35
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 34
- 239000013612 plasmid Substances 0.000 description 28
- 239000002585 base Substances 0.000 description 27
- 230000035882 stress Effects 0.000 description 27
- 239000008187 granular material Substances 0.000 description 26
- 108020001507 fusion proteins Proteins 0.000 description 25
- 102000037865 fusion proteins Human genes 0.000 description 25
- 239000005090 green fluorescent protein Substances 0.000 description 21
- 238000001727 in vivo Methods 0.000 description 21
- 238000005259 measurement Methods 0.000 description 21
- 239000000203 mixture Substances 0.000 description 20
- 238000009396 hybridization Methods 0.000 description 19
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
- 102000044126 RNA-Binding Proteins Human genes 0.000 description 18
- 239000000872 buffer Substances 0.000 description 18
- 229940088598 enzyme Drugs 0.000 description 18
- 230000004807 localization Effects 0.000 description 18
- 210000003205 muscle Anatomy 0.000 description 18
- 239000003153 chemical reaction reagent Substances 0.000 description 17
- 102000034287 fluorescent proteins Human genes 0.000 description 17
- 108091006047 fluorescent proteins Proteins 0.000 description 17
- 238000010362 genome editing Methods 0.000 description 17
- 230000014616 translation Effects 0.000 description 17
- 206010068871 Myotonic dystrophy Diseases 0.000 description 16
- 108091027544 Subgenomic mRNA Proteins 0.000 description 16
- 238000005516 engineering process Methods 0.000 description 16
- 108010048367 enhanced green fluorescent protein Proteins 0.000 description 16
- 239000003607 modifier Substances 0.000 description 16
- 230000014632 RNA localization Effects 0.000 description 15
- -1 and/or their analogs Substances 0.000 description 15
- 210000001519 tissue Anatomy 0.000 description 15
- 230000032258 transport Effects 0.000 description 15
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 14
- 206010028980 Neoplasm Diseases 0.000 description 14
- 239000000074 antisense oligonucleotide Substances 0.000 description 14
- 238000012230 antisense oligonucleotides Methods 0.000 description 14
- 238000013459 approach Methods 0.000 description 14
- 238000003776 cleavage reaction Methods 0.000 description 14
- 238000003384 imaging method Methods 0.000 description 14
- 102000040430 polynucleotide Human genes 0.000 description 14
- 108091033319 polynucleotide Proteins 0.000 description 14
- 239000002157 polynucleotide Substances 0.000 description 14
- 150000001413 amino acids Chemical class 0.000 description 13
- 238000002474 experimental method Methods 0.000 description 13
- 239000012528 membrane Substances 0.000 description 13
- 230000007017 scission Effects 0.000 description 13
- 230000001225 therapeutic effect Effects 0.000 description 13
- 208000002267 Anti-neutrophil cytoplasmic antibody-associated vasculitis Diseases 0.000 description 12
- 125000005647 linker group Chemical group 0.000 description 12
- 230000001404 mediated effect Effects 0.000 description 12
- 238000001890 transfection Methods 0.000 description 12
- 102100031780 Endonuclease Human genes 0.000 description 11
- 108010043121 Green Fluorescent Proteins Proteins 0.000 description 11
- 102000004144 Green Fluorescent Proteins Human genes 0.000 description 11
- 241000193996 Streptococcus pyogenes Species 0.000 description 11
- 238000009826 distribution Methods 0.000 description 11
- 239000000243 solution Substances 0.000 description 11
- 108060001084 Luciferase Proteins 0.000 description 10
- 239000005089 Luciferase Substances 0.000 description 10
- 108700020471 RNA-Binding Proteins Proteins 0.000 description 10
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 10
- 201000011510 cancer Diseases 0.000 description 10
- 210000000805 cytoplasm Anatomy 0.000 description 10
- 239000012634 fragment Substances 0.000 description 10
- 238000002347 injection Methods 0.000 description 10
- 239000007924 injection Substances 0.000 description 10
- 230000004048 modification Effects 0.000 description 10
- 238000012986 modification Methods 0.000 description 10
- 210000004940 nucleus Anatomy 0.000 description 10
- 208000002320 spinal muscular atrophy Diseases 0.000 description 10
- 238000010453 CRISPR/Cas method Methods 0.000 description 9
- 101710125418 Major capsid protein Proteins 0.000 description 9
- 108010052090 Renilla Luciferases Proteins 0.000 description 9
- 235000001014 amino acid Nutrition 0.000 description 9
- 230000000692 anti-sense effect Effects 0.000 description 9
- 230000001413 cellular effect Effects 0.000 description 9
- 230000001086 cytosolic effect Effects 0.000 description 9
- 238000013461 design Methods 0.000 description 9
- 230000006870 function Effects 0.000 description 9
- 230000004927 fusion Effects 0.000 description 9
- 239000003550 marker Substances 0.000 description 9
- 238000012216 screening Methods 0.000 description 9
- 101710159080 Aconitate hydratase A Proteins 0.000 description 8
- 101710159078 Aconitate hydratase B Proteins 0.000 description 8
- 108020000948 Antisense Oligonucleotides Proteins 0.000 description 8
- 241000894006 Bacteria Species 0.000 description 8
- 241000701022 Cytomegalovirus Species 0.000 description 8
- 101000617738 Homo sapiens Survival motor neuron protein Proteins 0.000 description 8
- 241000699666 Mus <mouse, genus> Species 0.000 description 8
- 101710105008 RNA-binding protein Proteins 0.000 description 8
- 102100021947 Survival motor neuron protein Human genes 0.000 description 8
- 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 8
- 238000004458 analytical method Methods 0.000 description 8
- 239000011324 bead Substances 0.000 description 8
- 230000006378 damage Effects 0.000 description 8
- 238000011161 development Methods 0.000 description 8
- 230000018109 developmental process Effects 0.000 description 8
- 239000003814 drug Substances 0.000 description 8
- 230000003993 interaction Effects 0.000 description 8
- 238000012545 processing Methods 0.000 description 8
- 230000001177 retroviral effect Effects 0.000 description 8
- 239000000758 substrate Substances 0.000 description 8
- 235000000346 sugar Nutrition 0.000 description 8
- 238000002560 therapeutic procedure Methods 0.000 description 8
- 230000035897 transcription Effects 0.000 description 8
- 238000013518 transcription Methods 0.000 description 8
- 101710132601 Capsid protein Proteins 0.000 description 7
- 101710094648 Coat protein Proteins 0.000 description 7
- 101150064904 FOX2 gene Proteins 0.000 description 7
- 102100021181 Golgi phosphoprotein 3 Human genes 0.000 description 7
- 208000023105 Huntington disease Diseases 0.000 description 7
- 101710141454 Nucleoprotein Proteins 0.000 description 7
- 101710083689 Probable capsid protein Proteins 0.000 description 7
- 238000012228 RNA interference-mediated gene silencing Methods 0.000 description 7
- 241000700605 Viruses Species 0.000 description 7
- 230000035508 accumulation Effects 0.000 description 7
- 238000009825 accumulation Methods 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 7
- 238000001514 detection method Methods 0.000 description 7
- 210000003527 eukaryotic cell Anatomy 0.000 description 7
- 230000009368 gene silencing by RNA Effects 0.000 description 7
- 101150007867 rbfox2 gene Proteins 0.000 description 7
- 238000012800 visualization Methods 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- 108020005345 3' Untranslated Regions Proteins 0.000 description 6
- 239000013607 AAV vector Substances 0.000 description 6
- 108091023037 Aptamer Proteins 0.000 description 6
- 208000037065 Subacute sclerosing leukoencephalitis Diseases 0.000 description 6
- 206010042297 Subacute sclerosing panencephalitis Diseases 0.000 description 6
- 108091023045 Untranslated Region Proteins 0.000 description 6
- 230000006399 behavior Effects 0.000 description 6
- 230000008045 co-localization Effects 0.000 description 6
- 230000001419 dependent effect Effects 0.000 description 6
- 230000002068 genetic effect Effects 0.000 description 6
- 238000007901 in situ hybridization Methods 0.000 description 6
- 238000002955 isolation Methods 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- 210000002569 neuron Anatomy 0.000 description 6
- 230000030147 nuclear export Effects 0.000 description 6
- 238000000746 purification Methods 0.000 description 6
- PTLRDCMBXHILCL-UHFFFAOYSA-M sodium arsenite Chemical compound [Na+].[O-][As]=O PTLRDCMBXHILCL-UHFFFAOYSA-M 0.000 description 6
- 238000010356 CRISPR-Cas9 genome editing Methods 0.000 description 5
- 208000001914 Fragile X syndrome Diseases 0.000 description 5
- 102100031181 Glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 5
- 108700011259 MicroRNAs Proteins 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 101710120037 Toxin CcdB Proteins 0.000 description 5
- 108020004566 Transfer RNA Proteins 0.000 description 5
- 230000033228 biological regulation Effects 0.000 description 5
- 210000004899 c-terminal region Anatomy 0.000 description 5
- 210000003855 cell nucleus Anatomy 0.000 description 5
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 5
- 238000003780 insertion Methods 0.000 description 5
- 230000037431 insertion Effects 0.000 description 5
- 238000012544 monitoring process Methods 0.000 description 5
- 239000008188 pellet Substances 0.000 description 5
- 229920000642 polymer Polymers 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 230000010076 replication Effects 0.000 description 5
- 230000002441 reversible effect Effects 0.000 description 5
- 125000006850 spacer group Chemical group 0.000 description 5
- 239000006228 supernatant Substances 0.000 description 5
- 238000011830 transgenic mouse model Methods 0.000 description 5
- 241001515965 unidentified phage Species 0.000 description 5
- 239000013603 viral vector Substances 0.000 description 5
- 241000203069 Archaea Species 0.000 description 4
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 4
- 102000014914 Carrier Proteins Human genes 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 102000053602 DNA Human genes 0.000 description 4
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 4
- 108700024394 Exon Proteins 0.000 description 4
- 101000583839 Homo sapiens Muscleblind-like protein 1 Proteins 0.000 description 4
- 102100030965 Muscleblind-like protein 1 Human genes 0.000 description 4
- 108700026244 Open Reading Frames Proteins 0.000 description 4
- 230000004570 RNA-binding Effects 0.000 description 4
- 235000011449 Rosa Nutrition 0.000 description 4
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 4
- 108091046869 Telomeric non-coding RNA Proteins 0.000 description 4
- 108700019146 Transgenes Proteins 0.000 description 4
- 230000009471 action Effects 0.000 description 4
- 238000001042 affinity chromatography Methods 0.000 description 4
- 108091008324 binding proteins Proteins 0.000 description 4
- 230000008859 change Effects 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 238000004624 confocal microscopy Methods 0.000 description 4
- 238000010276 construction Methods 0.000 description 4
- 230000002950 deficient Effects 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 230000001965 increasing effect Effects 0.000 description 4
- 230000000670 limiting effect Effects 0.000 description 4
- 230000007246 mechanism Effects 0.000 description 4
- 238000010172 mouse model Methods 0.000 description 4
- 201000009340 myotonic dystrophy type 1 Diseases 0.000 description 4
- 230000003274 myotonic effect Effects 0.000 description 4
- 239000002105 nanoparticle Substances 0.000 description 4
- 239000013642 negative control Substances 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- RXWNCPJZOCPEPQ-NVWDDTSBSA-N puromycin Chemical compound C1=CC(OC)=CC=C1C[C@H](N)C(=O)N[C@H]1[C@@H](O)[C@H](N2C3=NC=NC(=C3N=C2)N(C)C)O[C@@H]1CO RXWNCPJZOCPEPQ-NVWDDTSBSA-N 0.000 description 4
- 238000011002 quantification Methods 0.000 description 4
- 230000001105 regulatory effect Effects 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- 230000004044 response Effects 0.000 description 4
- 238000003757 reverse transcription PCR Methods 0.000 description 4
- 230000009870 specific binding Effects 0.000 description 4
- 230000008093 supporting effect Effects 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- 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 3
- 108010085238 Actins Proteins 0.000 description 3
- 102000043334 C9orf72 Human genes 0.000 description 3
- 108700030955 C9orf72 Proteins 0.000 description 3
- 101150014718 C9orf72 gene Proteins 0.000 description 3
- 108091026890 Coding region Proteins 0.000 description 3
- 108020003215 DNA Probes Proteins 0.000 description 3
- 239000003298 DNA probe Substances 0.000 description 3
- 230000004568 DNA-binding Effects 0.000 description 3
- 108700019745 Disks Large Homolog 4 Proteins 0.000 description 3
- 102000047174 Disks Large Homolog 4 Human genes 0.000 description 3
- 241000588724 Escherichia coli Species 0.000 description 3
- 102000016359 Fibronectins Human genes 0.000 description 3
- 108010067306 Fibronectins Proteins 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- 102000007338 Fragile X Mental Retardation Protein Human genes 0.000 description 3
- 108010032606 Fragile X Mental Retardation Protein Proteins 0.000 description 3
- 101710162684 Glyceraldehyde-3-phosphate dehydrogenase 3 Proteins 0.000 description 3
- 102100037924 Insulin-like growth factor 2 mRNA-binding protein 1 Human genes 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 241000699660 Mus musculus Species 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- 206010061533 Myotonia Diseases 0.000 description 3
- 102100022437 Myotonin-protein kinase Human genes 0.000 description 3
- 208000009869 Neu-Laxova syndrome Diseases 0.000 description 3
- 239000004677 Nylon Substances 0.000 description 3
- 102100040854 Ras GTPase-activating protein-binding protein 1 Human genes 0.000 description 3
- 108091081024 Start codon Proteins 0.000 description 3
- 108091036066 Three prime untranslated region Proteins 0.000 description 3
- 108020000999 Viral RNA Proteins 0.000 description 3
- 210000005006 adaptive immune system Anatomy 0.000 description 3
- 101150063416 add gene Proteins 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 229910002091 carbon monoxide Inorganic materials 0.000 description 3
- 210000003169 central nervous system Anatomy 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 210000000349 chromosome Anatomy 0.000 description 3
- 239000002299 complementary DNA Substances 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 230000001066 destructive effect Effects 0.000 description 3
- 239000003623 enhancer Substances 0.000 description 3
- 239000013604 expression vector Substances 0.000 description 3
- 238000010353 genetic engineering Methods 0.000 description 3
- 239000011521 glass Substances 0.000 description 3
- 230000033001 locomotion Effects 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 230000002503 metabolic effect Effects 0.000 description 3
- 150000002739 metals Chemical class 0.000 description 3
- 239000002679 microRNA Substances 0.000 description 3
- 238000010369 molecular cloning Methods 0.000 description 3
- 230000004770 neurodegeneration Effects 0.000 description 3
- 108091027963 non-coding RNA Proteins 0.000 description 3
- 102000042567 non-coding RNA Human genes 0.000 description 3
- 229920001778 nylon Polymers 0.000 description 3
- 230000008520 organization Effects 0.000 description 3
- 125000006239 protecting group Chemical group 0.000 description 3
- 108020001580 protein domains Proteins 0.000 description 3
- 230000006916 protein interaction Effects 0.000 description 3
- 230000008929 regeneration Effects 0.000 description 3
- 238000011069 regeneration method Methods 0.000 description 3
- 238000002473 ribonucleic acid immunoprecipitation Methods 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 150000008163 sugars Chemical class 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 230000002103 transcriptional effect Effects 0.000 description 3
- 230000003612 virological effect Effects 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 2
- 102000007469 Actins Human genes 0.000 description 2
- HJCMDXDYPOUFDY-WHFBIAKZSA-N Ala-Gln Chemical compound C[C@H](N)C(=O)N[C@H](C(O)=O)CCC(N)=O HJCMDXDYPOUFDY-WHFBIAKZSA-N 0.000 description 2
- 108700028369 Alleles Proteins 0.000 description 2
- 108020005544 Antisense RNA Proteins 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 108091079001 CRISPR RNA Proteins 0.000 description 2
- 238000010446 CRISPR interference Methods 0.000 description 2
- 108091006146 Channels Proteins 0.000 description 2
- 108020004705 Codon Proteins 0.000 description 2
- 101710192476 Cytoplasmic polyadenylation element-binding protein Proteins 0.000 description 2
- 102220605874 Cytosolic arginine sensor for mTORC1 subunit 2_D10A_mutation Human genes 0.000 description 2
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 2
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 2
- 241000252212 Danio rerio Species 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 206010059866 Drug resistance Diseases 0.000 description 2
- 241000709744 Enterobacterio phage MS2 Species 0.000 description 2
- 241000206602 Eukaryota Species 0.000 description 2
- 101710154606 Hemagglutinin Proteins 0.000 description 2
- 108010093488 His-His-His-His-His-His Proteins 0.000 description 2
- 102100026265 Histone-lysine N-methyltransferase ASH1L Human genes 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 101000901099 Homo sapiens Achaete-scute homolog 1 Proteins 0.000 description 2
- 101000785963 Homo sapiens Histone-lysine N-methyltransferase ASH1L Proteins 0.000 description 2
- 101000599778 Homo sapiens Insulin-like growth factor 2 mRNA-binding protein 1 Proteins 0.000 description 2
- 101000988591 Homo sapiens Minor histocompatibility antigen H13 Proteins 0.000 description 2
- 108060003951 Immunoglobulin Proteins 0.000 description 2
- 238000000636 Northern blotting Methods 0.000 description 2
- 101710093908 Outer capsid protein VP4 Proteins 0.000 description 2
- 101710135467 Outer capsid protein sigma-1 Proteins 0.000 description 2
- 229930040373 Paraformaldehyde Natural products 0.000 description 2
- 108091093037 Peptide nucleic acid Proteins 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 101710176177 Protein A56 Proteins 0.000 description 2
- 108010029485 Protein Isoforms Proteins 0.000 description 2
- 102000001708 Protein Isoforms Human genes 0.000 description 2
- 108010076504 Protein Sorting Signals Proteins 0.000 description 2
- 102000017742 Pumilio homology domains Human genes 0.000 description 2
- 108050005947 Pumilio homology domains Proteins 0.000 description 2
- 239000012083 RIPA buffer Substances 0.000 description 2
- 238000011529 RT qPCR Methods 0.000 description 2
- 108050003637 Ras GTPase-activating protein-binding protein 1 Proteins 0.000 description 2
- 241000242739 Renilla Species 0.000 description 2
- 102000006382 Ribonucleases Human genes 0.000 description 2
- 108010083644 Ribonucleases Proteins 0.000 description 2
- 102000039471 Small Nuclear RNA Human genes 0.000 description 2
- 108091027967 Small hairpin RNA Proteins 0.000 description 2
- 208000009415 Spinocerebellar Ataxias Diseases 0.000 description 2
- RYYWUUFWQRZTIU-UHFFFAOYSA-N Thiophosphoric acid Chemical class OP(O)(S)=O RYYWUUFWQRZTIU-UHFFFAOYSA-N 0.000 description 2
- 108010022394 Threonine synthase Proteins 0.000 description 2
- 108091046915 Threose nucleic acid 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
- 241000723792 Tobacco etch virus Species 0.000 description 2
- 108091028113 Trans-activating crRNA Proteins 0.000 description 2
- 108091026822 U6 spliceosomal RNA Proteins 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
- 230000001594 aberrant effect Effects 0.000 description 2
- DZBUGLKDJFMEHC-UHFFFAOYSA-N acridine Chemical compound C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 description 2
- 125000000539 amino acid group Chemical group 0.000 description 2
- 230000003321 amplification Effects 0.000 description 2
- 210000004102 animal cell Anatomy 0.000 description 2
- 238000000376 autoradiography Methods 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- 229940098773 bovine serum albumin Drugs 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 210000000170 cell membrane Anatomy 0.000 description 2
- 210000002421 cell wall Anatomy 0.000 description 2
- 238000010367 cloning Methods 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 238000012217 deletion Methods 0.000 description 2
- 230000037430 deletion Effects 0.000 description 2
- 229960000633 dextran sulfate Drugs 0.000 description 2
- 102000004419 dihydrofolate reductase Human genes 0.000 description 2
- 238000009510 drug design Methods 0.000 description 2
- 238000009509 drug development Methods 0.000 description 2
- 230000009977 dual effect Effects 0.000 description 2
- 239000003797 essential amino acid Substances 0.000 description 2
- 235000020776 essential amino acid Nutrition 0.000 description 2
- 230000017188 evasion or tolerance of host immune response Effects 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 239000012091 fetal bovine serum Substances 0.000 description 2
- 238000000799 fluorescence microscopy Methods 0.000 description 2
- 230000030279 gene silencing Effects 0.000 description 2
- 238000010363 gene targeting Methods 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical compound O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 description 2
- 102000018358 immunoglobulin Human genes 0.000 description 2
- 230000001976 improved effect Effects 0.000 description 2
- 238000010348 incorporation Methods 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 238000007917 intracranial administration Methods 0.000 description 2
- PHTQWCKDNZKARW-UHFFFAOYSA-N isoamylol Chemical compound CC(C)CCO PHTQWCKDNZKARW-UHFFFAOYSA-N 0.000 description 2
- QWTDNUCVQCZILF-UHFFFAOYSA-N isopentane Chemical compound CCC(C)C QWTDNUCVQCZILF-UHFFFAOYSA-N 0.000 description 2
- 238000002372 labelling Methods 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 239000002502 liposome Substances 0.000 description 2
- 238000010859 live-cell imaging Methods 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 102000033952 mRNA binding proteins Human genes 0.000 description 2
- 108091000373 mRNA binding proteins Proteins 0.000 description 2
- 210000005171 mammalian brain Anatomy 0.000 description 2
- 238000013507 mapping Methods 0.000 description 2
- YACKEPLHDIMKIO-UHFFFAOYSA-N methylphosphonic acid Chemical class CP(O)(O)=O YACKEPLHDIMKIO-UHFFFAOYSA-N 0.000 description 2
- 238000009126 molecular therapy Methods 0.000 description 2
- 239000012120 mounting media Substances 0.000 description 2
- 210000000653 nervous system Anatomy 0.000 description 2
- 230000001537 neural effect Effects 0.000 description 2
- 230000005015 neuronal process Effects 0.000 description 2
- 238000003199 nucleic acid amplification method Methods 0.000 description 2
- 230000001293 nucleolytic effect Effects 0.000 description 2
- 230000036542 oxidative stress Effects 0.000 description 2
- 229920002866 paraformaldehyde Polymers 0.000 description 2
- 230000036961 partial effect Effects 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 230000008506 pathogenesis Effects 0.000 description 2
- 230000001717 pathogenic effect Effects 0.000 description 2
- 230000006320 pegylation Effects 0.000 description 2
- 230000002085 persistent effect Effects 0.000 description 2
- 150000004713 phosphodiesters Chemical group 0.000 description 2
- 230000001124 posttranscriptional effect Effects 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- 235000004252 protein component Nutrition 0.000 description 2
- ZCCUUQDIBDJBTK-UHFFFAOYSA-N psoralen Chemical compound C1=C2OC(=O)C=CC2=CC2=C1OC=C2 ZCCUUQDIBDJBTK-UHFFFAOYSA-N 0.000 description 2
- 229950010131 puromycin Drugs 0.000 description 2
- 230000003938 response to stress Effects 0.000 description 2
- 108020004418 ribosomal RNA Proteins 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 230000011664 signaling Effects 0.000 description 2
- 229910052709 silver Inorganic materials 0.000 description 2
- 239000004332 silver Substances 0.000 description 2
- 239000004055 small Interfering RNA Substances 0.000 description 2
- 150000003384 small molecules Chemical class 0.000 description 2
- 108091029842 small nuclear ribonucleic acid Proteins 0.000 description 2
- 101150044104 soc gene Proteins 0.000 description 2
- 239000001488 sodium phosphate Substances 0.000 description 2
- 229910000162 sodium phosphate Inorganic materials 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 210000000130 stem cell Anatomy 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 230000000946 synaptic effect Effects 0.000 description 2
- 239000003053 toxin Substances 0.000 description 2
- 231100000765 toxin Toxicity 0.000 description 2
- 108700012359 toxins Proteins 0.000 description 2
- 230000005026 transcription initiation Effects 0.000 description 2
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 2
- 230000010415 tropism Effects 0.000 description 2
- 238000010200 validation analysis Methods 0.000 description 2
- 230000001018 virulence Effects 0.000 description 2
- 108091005957 yellow fluorescent proteins Proteins 0.000 description 2
- 229910052725 zinc Inorganic materials 0.000 description 2
- 239000011701 zinc Substances 0.000 description 2
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- KJTLQQUUPVSXIM-ZCFIWIBFSA-M (R)-mevalonate Chemical compound OCC[C@](O)(C)CC([O-])=O KJTLQQUUPVSXIM-ZCFIWIBFSA-M 0.000 description 1
- YMHOBZXQZVXHBM-UHFFFAOYSA-N 2,5-dimethoxy-4-bromophenethylamine Chemical compound COC1=CC(CCN)=C(OC)C=C1Br YMHOBZXQZVXHBM-UHFFFAOYSA-N 0.000 description 1
- SGTNSNPWRIOYBX-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino}-2-(propan-2-yl)pentanenitrile Chemical compound C1=C(OC)C(OC)=CC=C1CCN(C)CCCC(C#N)(C(C)C)C1=CC=C(OC)C(OC)=C1 SGTNSNPWRIOYBX-UHFFFAOYSA-N 0.000 description 1
- VXGRJERITKFWPL-UHFFFAOYSA-N 4',5'-Dihydropsoralen Natural products C1=C2OC(=O)C=CC2=CC2=C1OCC2 VXGRJERITKFWPL-UHFFFAOYSA-N 0.000 description 1
- 208000035657 Abasia Diseases 0.000 description 1
- 101710197637 Actin-3 Proteins 0.000 description 1
- OIRDTQYFTABQOQ-KQYNXXCUSA-N Adenosine Natural products C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 1
- 206010001497 Agitation Diseases 0.000 description 1
- 208000009575 Angelman syndrome Diseases 0.000 description 1
- 101000760456 Anguilla japonica Bilirubin-inducible fluorescent protein UnaG Proteins 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 102000008682 Argonaute Proteins Human genes 0.000 description 1
- 108010088141 Argonaute Proteins Proteins 0.000 description 1
- 206010003591 Ataxia Diseases 0.000 description 1
- 206010003805 Autism Diseases 0.000 description 1
- 208000020706 Autistic disease Diseases 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 108091005950 Azurite Proteins 0.000 description 1
- 241000193830 Bacillus <bacterium> Species 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
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 1
- 101100028791 Caenorhabditis elegans pbs-5 gene Proteins 0.000 description 1
- 101710167800 Capsid assembly scaffolding protein Proteins 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 208000020446 Cardiac disease Diseases 0.000 description 1
- 108091005944 Cerulean Proteins 0.000 description 1
- 102000018424 Chloride channel ClC-1 Human genes 0.000 description 1
- 108050007520 Chloride channel ClC-1 Proteins 0.000 description 1
- 108010077544 Chromatin Proteins 0.000 description 1
- 108091035707 Consensus sequence Proteins 0.000 description 1
- 241000699802 Cricetulus griseus Species 0.000 description 1
- 108091005943 CyPet Proteins 0.000 description 1
- 102100032620 Cytotoxic granule associated RNA binding protein TIA1 Human genes 0.000 description 1
- 101710086368 Cytotoxic granule associated RNA binding protein TIA1 Proteins 0.000 description 1
- HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 description 1
- KJTLQQUUPVSXIM-UHFFFAOYSA-N DL-mevalonic acid Natural products OCCC(O)(C)CC(O)=O KJTLQQUUPVSXIM-UHFFFAOYSA-N 0.000 description 1
- 238000010442 DNA editing Methods 0.000 description 1
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 1
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 1
- 102000016607 Diphtheria Toxin Human genes 0.000 description 1
- 108010053187 Diphtheria Toxin Proteins 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 101100408379 Drosophila melanogaster piwi gene Proteins 0.000 description 1
- 108091005941 EBFP Proteins 0.000 description 1
- 108091005947 EBFP2 Proteins 0.000 description 1
- 101150059079 EBNA1 gene Proteins 0.000 description 1
- 108091005942 ECFP Proteins 0.000 description 1
- 108010067770 Endopeptidase K Proteins 0.000 description 1
- 102100030013 Endoribonuclease Human genes 0.000 description 1
- 108010093099 Endoribonucleases Proteins 0.000 description 1
- GTAXGNCCEYZRII-UHFFFAOYSA-N Eperisone hydrochloride Chemical compound Cl.C1=CC(CC)=CC=C1C(=O)C(C)CN1CCCCC1 GTAXGNCCEYZRII-UHFFFAOYSA-N 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
- 241000701959 Escherichia virus Lambda Species 0.000 description 1
- 229920001917 Ficoll Polymers 0.000 description 1
- 108090000331 Firefly luciferases Proteins 0.000 description 1
- 201000011240 Frontotemporal dementia Diseases 0.000 description 1
- 108091006027 G proteins Proteins 0.000 description 1
- 102100038392 GRAM domain-containing protein 4 Human genes 0.000 description 1
- 101710192658 GRAM domain-containing protein 4 Proteins 0.000 description 1
- 102000030782 GTP binding Human genes 0.000 description 1
- 108091000058 GTP-Binding Proteins 0.000 description 1
- 241000963438 Gaussia <copepod> Species 0.000 description 1
- 108700028146 Genetic Enhancer Elements Proteins 0.000 description 1
- 108091093094 Glycol nucleic acid Proteins 0.000 description 1
- 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 1
- 102100027377 HBS1-like protein Human genes 0.000 description 1
- 238000012156 HITS-CLIP Methods 0.000 description 1
- 108010014594 Heterogeneous Nuclear Ribonucleoprotein A1 Proteins 0.000 description 1
- 102000017013 Heterogeneous Nuclear Ribonucleoprotein A1 Human genes 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 101001009070 Homo sapiens HBS1-like protein Proteins 0.000 description 1
- 101001030705 Homo sapiens Huntingtin Proteins 0.000 description 1
- 101000599782 Homo sapiens Insulin-like growth factor 2 mRNA-binding protein 3 Proteins 0.000 description 1
- 101000960626 Homo sapiens Mitochondrial inner membrane protease subunit 2 Proteins 0.000 description 1
- 101000665449 Homo sapiens RNA binding protein fox-1 homolog 1 Proteins 0.000 description 1
- 101000893689 Homo sapiens Ras GTPase-activating protein-binding protein 1 Proteins 0.000 description 1
- 101100203485 Homo sapiens SMN2 gene Proteins 0.000 description 1
- 101000702394 Homo sapiens Signal peptide peptidase-like 2A Proteins 0.000 description 1
- 101000828788 Homo sapiens Signal peptide peptidase-like 3 Proteins 0.000 description 1
- 101001063514 Homo sapiens Telomerase-binding protein EST1A Proteins 0.000 description 1
- 101000960621 Homo sapiens U3 small nucleolar ribonucleoprotein protein IMP3 Proteins 0.000 description 1
- 101000964436 Homo sapiens Z-DNA-binding protein 1 Proteins 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 241000282619 Hylobates lar Species 0.000 description 1
- UGQMRVRMYYASKQ-UHFFFAOYSA-N Hypoxanthine nucleoside Natural products OC1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 UGQMRVRMYYASKQ-UHFFFAOYSA-N 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- 208000026350 Inborn Genetic disease Diseases 0.000 description 1
- 102000048143 Insulin-Like Growth Factor II Human genes 0.000 description 1
- 108090001117 Insulin-Like Growth Factor II Proteins 0.000 description 1
- 102100034343 Integrase Human genes 0.000 description 1
- 101710203526 Integrase Proteins 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- 241000254158 Lampyridae Species 0.000 description 1
- 102000006830 Luminescent Proteins Human genes 0.000 description 1
- 108010047357 Luminescent Proteins Proteins 0.000 description 1
- 238000000585 Mann–Whitney U test Methods 0.000 description 1
- 108091027974 Mature messenger RNA Proteins 0.000 description 1
- 102000016193 Metabotropic glutamate receptors Human genes 0.000 description 1
- 108010010914 Metabotropic glutamate receptors Proteins 0.000 description 1
- 108010085220 Multiprotein Complexes Proteins 0.000 description 1
- 102000007474 Multiprotein Complexes Human genes 0.000 description 1
- 108091061960 Naked DNA Proteins 0.000 description 1
- 241000169176 Natronobacterium gregoryi Species 0.000 description 1
- 229930193140 Neomycin Natural products 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- 241001276274 Nitratifractor salsuginis DSM 16511 Species 0.000 description 1
- 108091092724 Noncoding DNA Proteins 0.000 description 1
- 102000007999 Nuclear Proteins Human genes 0.000 description 1
- 108010089610 Nuclear Proteins Proteins 0.000 description 1
- 108091005461 Nucleic proteins Proteins 0.000 description 1
- 201000009110 Oculopharyngeal muscular dystrophy Diseases 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 238000012879 PET imaging Methods 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 108010077524 Peptide Elongation Factor 1 Proteins 0.000 description 1
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical group OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 101710130420 Probable capsid assembly scaffolding protein Proteins 0.000 description 1
- 108010007568 Protamines Proteins 0.000 description 1
- 102000007327 Protamines Human genes 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
- 101100084022 Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1) lapA gene Proteins 0.000 description 1
- 241000205156 Pyrococcus furiosus Species 0.000 description 1
- 108091034057 RNA (poly(A)) Proteins 0.000 description 1
- 102000008991 RNA Recognition Motif Proteins Human genes 0.000 description 1
- 108010049094 RNA Recognition Motif Proteins Proteins 0.000 description 1
- 108091008103 RNA aptamers Proteins 0.000 description 1
- 238000010357 RNA editing Methods 0.000 description 1
- 230000026279 RNA modification Effects 0.000 description 1
- 238000003559 RNA-seq method Methods 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 101000599776 Rattus norvegicus Insulin-like growth factor 2 mRNA-binding protein 1 Proteins 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 108091081062 Repeated sequence (DNA) Proteins 0.000 description 1
- 108700008625 Reporter Genes Proteins 0.000 description 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
- 108091028664 Ribonucleotide Proteins 0.000 description 1
- PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 1
- 230000018199 S phase Effects 0.000 description 1
- 101150081851 SMN1 gene Proteins 0.000 description 1
- 101710204410 Scaffold protein Proteins 0.000 description 1
- 101710184528 Scaffolding protein Proteins 0.000 description 1
- 108091081021 Sense strand Proteins 0.000 description 1
- 102100030403 Signal peptide peptidase-like 2A Human genes 0.000 description 1
- 102100023501 Signal peptide peptidase-like 3 Human genes 0.000 description 1
- 108091061750 Signal recognition particle RNA Proteins 0.000 description 1
- 108020004682 Single-Stranded DNA Proteins 0.000 description 1
- 108020004459 Small interfering RNA Proteins 0.000 description 1
- 208000037140 Steinert myotonic dystrophy Diseases 0.000 description 1
- 101000910035 Streptococcus pyogenes serotype M1 CRISPR-associated endonuclease Cas9/Csn1 Proteins 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 238000010459 TALEN Methods 0.000 description 1
- 241001520689 Tanichthys albonubes Species 0.000 description 1
- 239000004098 Tetracycline Substances 0.000 description 1
- 241000589499 Thermus thermophilus Species 0.000 description 1
- 201000008188 Timothy syndrome Diseases 0.000 description 1
- 108010043645 Transcription Activator-Like Effector Nucleases Proteins 0.000 description 1
- 108700009124 Transcription Initiation Site Proteins 0.000 description 1
- 102100037116 Transcription elongation factor 1 homolog Human genes 0.000 description 1
- 206010044565 Tremor Diseases 0.000 description 1
- 208000003721 Triple Negative Breast Neoplasms Diseases 0.000 description 1
- 108090000848 Ubiquitin Proteins 0.000 description 1
- 102000044159 Ubiquitin Human genes 0.000 description 1
- 241000545067 Venus Species 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 241000269457 Xenopus tropicalis Species 0.000 description 1
- 108010017070 Zinc Finger Nucleases Proteins 0.000 description 1
- 230000003187 abdominal effect Effects 0.000 description 1
- 238000002679 ablation Methods 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
- 150000001241 acetals Chemical group 0.000 description 1
- FRTNIYVUDIHXPG-UHFFFAOYSA-N acetic acid;ethane-1,2-diamine Chemical compound CC(O)=O.CC(O)=O.CC(O)=O.CC(O)=O.NCCN FRTNIYVUDIHXPG-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 125000002015 acyclic group Chemical group 0.000 description 1
- 229960005305 adenosine Drugs 0.000 description 1
- 239000011543 agarose gel Substances 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 description 1
- 230000001668 ameliorated effect Effects 0.000 description 1
- 229940059260 amidate Drugs 0.000 description 1
- 150000001412 amines Chemical group 0.000 description 1
- 229960000723 ampicillin Drugs 0.000 description 1
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 1
- 238000004873 anchoring Methods 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- 230000000890 antigenic 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
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 238000003491 array Methods 0.000 description 1
- 210000004507 artificial chromosome Anatomy 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000000712 assembly Effects 0.000 description 1
- 238000000429 assembly Methods 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 208000029560 autism spectrum disease Diseases 0.000 description 1
- 210000003050 axon Anatomy 0.000 description 1
- 230000003376 axonal effect Effects 0.000 description 1
- 230000008970 bacterial immunity 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
- 230000008436 biogenesis Effects 0.000 description 1
- 229940125385 biologic drug Drugs 0.000 description 1
- 239000000090 biomarker Substances 0.000 description 1
- 238000001574 biopsy Methods 0.000 description 1
- 230000001851 biosynthetic effect Effects 0.000 description 1
- 230000006696 biosynthetic metabolic pathway Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 108091005948 blue fluorescent proteins Proteins 0.000 description 1
- 229910052796 boron Inorganic materials 0.000 description 1
- 230000004641 brain development Effects 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- DQXBYHZEEUGOBF-UHFFFAOYSA-N but-3-enoic acid;ethene Chemical compound C=C.OC(=O)CC=C DQXBYHZEEUGOBF-UHFFFAOYSA-N 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 125000002837 carbocyclic group Chemical group 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 210000004413 cardiac myocyte Anatomy 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 229920006317 cationic polymer Polymers 0.000 description 1
- 210000005056 cell body Anatomy 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 210000004671 cell-free system Anatomy 0.000 description 1
- 230000036755 cellular response Effects 0.000 description 1
- 230000004637 cellular stress Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 125000003636 chemical group Chemical group 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
- 210000003483 chromatin Anatomy 0.000 description 1
- 239000003593 chromogenic compound Substances 0.000 description 1
- 230000008711 chromosomal rearrangement Effects 0.000 description 1
- 230000004186 co-expression Effects 0.000 description 1
- 239000003184 complementary RNA Substances 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 108010082025 cyan fluorescent protein Proteins 0.000 description 1
- 125000000392 cycloalkenyl group Chemical group 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 230000003436 cytoskeletal effect Effects 0.000 description 1
- 210000004292 cytoskeleton Anatomy 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 231100000599 cytotoxic agent Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 239000002619 cytotoxin Substances 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 239000003405 delayed action preparation Substances 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 210000001787 dendrite Anatomy 0.000 description 1
- 239000005547 deoxyribonucleotide Substances 0.000 description 1
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 1
- 230000001687 destabilization Effects 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- AFABGHUZZDYHJO-UHFFFAOYSA-N dimethyl butane Natural products CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- NAGJZTKCGNOGPW-UHFFFAOYSA-N dithiophosphoric acid Chemical class OP(O)(S)=S NAGJZTKCGNOGPW-UHFFFAOYSA-N 0.000 description 1
- 238000007877 drug screening Methods 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 238000002567 electromyography Methods 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- 230000002616 endonucleolytic effect Effects 0.000 description 1
- 210000002472 endoplasmic reticulum Anatomy 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 239000005038 ethylene vinyl acetate Substances 0.000 description 1
- NPUKDXXFDDZOKR-LLVKDONJSA-N etomidate Chemical compound CCOC(=O)C1=CN=CN1[C@H](C)C1=CC=CC=C1 NPUKDXXFDDZOKR-LLVKDONJSA-N 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000007667 floating Methods 0.000 description 1
- 238000002866 fluorescence resonance energy transfer Methods 0.000 description 1
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 1
- 238000002509 fluorescent in situ hybridization Methods 0.000 description 1
- 230000004907 flux Effects 0.000 description 1
- 210000003194 forelimb Anatomy 0.000 description 1
- 208000013967 frontotemporal dementia and/or amyotrophic lateral sclerosis 1 Diseases 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 238000011223 gene expression profiling Methods 0.000 description 1
- 238000003197 gene knockdown Methods 0.000 description 1
- 238000012239 gene modification Methods 0.000 description 1
- 238000002695 general anesthesia Methods 0.000 description 1
- 208000016361 genetic disease Diseases 0.000 description 1
- 230000005017 genetic modification Effects 0.000 description 1
- 238000012248 genetic selection Methods 0.000 description 1
- 235000013617 genetically modified food Nutrition 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 239000000185 hemagglutinin Substances 0.000 description 1
- 238000000703 high-speed centrifugation Methods 0.000 description 1
- 108010025934 hnRNP A2 Proteins 0.000 description 1
- 102000054185 human HTT Human genes 0.000 description 1
- 102000050025 human RBFOX1 Human genes 0.000 description 1
- 102000047899 human RBFOX2 Human genes 0.000 description 1
- 102000053564 human SMN2 Human genes 0.000 description 1
- 230000007954 hypoxia Effects 0.000 description 1
- 238000010191 image analysis Methods 0.000 description 1
- 230000003100 immobilizing effect Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 229940072221 immunoglobulins Drugs 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 206010022000 influenza Diseases 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 239000002198 insoluble material Substances 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 208000028774 intestinal disease Diseases 0.000 description 1
- 238000000185 intracerebroventricular administration Methods 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 238000007914 intraventricular administration Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 229960000318 kanamycin Drugs 0.000 description 1
- 229930027917 kanamycin Natural products 0.000 description 1
- SBUJHOSQTJFQJX-NOAMYHISSA-N kanamycin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N SBUJHOSQTJFQJX-NOAMYHISSA-N 0.000 description 1
- 229930182823 kanamycin A Natural products 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 210000003141 lower extremity Anatomy 0.000 description 1
- 150000002671 lyxoses Chemical class 0.000 description 1
- 108091005949 mKalama1 Proteins 0.000 description 1
- 108091005958 mTurquoise2 Proteins 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 230000000873 masking effect Effects 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 108091044988 miR-125a stem-loop Proteins 0.000 description 1
- 108091049513 miR-125a-1 stem-loop Proteins 0.000 description 1
- 108091040046 miR-125a-2 stem-loop Proteins 0.000 description 1
- 108091062762 miR-21 stem-loop Proteins 0.000 description 1
- 108091041631 miR-21-1 stem-loop Proteins 0.000 description 1
- 108091044442 miR-21-2 stem-loop Proteins 0.000 description 1
- 238000002493 microarray Methods 0.000 description 1
- 108091064355 mitochondrial RNA Proteins 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000009456 molecular mechanism Effects 0.000 description 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
- 230000004899 motility Effects 0.000 description 1
- 201000006938 muscular dystrophy Diseases 0.000 description 1
- 238000002703 mutagenesis Methods 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 229960004927 neomycin Drugs 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 230000007472 neurodevelopment Effects 0.000 description 1
- 230000016273 neuron death Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 102000044158 nucleic acid binding protein Human genes 0.000 description 1
- 108700020942 nucleic acid binding protein Proteins 0.000 description 1
- 238000007899 nucleic acid hybridization Methods 0.000 description 1
- 229940127073 nucleoside analogue Drugs 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 230000009437 off-target effect Effects 0.000 description 1
- 238000002515 oligonucleotide synthesis Methods 0.000 description 1
- 231100000590 oncogenic Toxicity 0.000 description 1
- 230000002246 oncogenic effect Effects 0.000 description 1
- 230000006548 oncogenic transformation Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 210000003463 organelle Anatomy 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 230000002688 persistence Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 101150009573 phoA gene Proteins 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
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
- 150000008300 phosphoramidites Chemical class 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 238000013492 plasmid preparation Methods 0.000 description 1
- 239000013600 plasmid vector Substances 0.000 description 1
- 229920000729 poly(L-lysine) polymer Polymers 0.000 description 1
- 229920001308 poly(aminoacid) Polymers 0.000 description 1
- 229920001200 poly(ethylene-vinyl acetate) Polymers 0.000 description 1
- 230000008488 polyadenylation Effects 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 230000004481 post-translational protein modification Effects 0.000 description 1
- 230000001242 postsynaptic effect Effects 0.000 description 1
- 230000003334 potential effect Effects 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000003518 presynaptic effect Effects 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 210000001236 prokaryotic cell Anatomy 0.000 description 1
- 229940048914 protamine Drugs 0.000 description 1
- 235000019419 proteases Nutrition 0.000 description 1
- 230000004952 protein activity Effects 0.000 description 1
- 238000003157 protein complementation Methods 0.000 description 1
- 230000016434 protein splicing Effects 0.000 description 1
- 230000012743 protein tagging Effects 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 1
- 238000006862 quantum yield reaction Methods 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 230000007115 recruitment Effects 0.000 description 1
- 108010054624 red fluorescent protein Proteins 0.000 description 1
- 230000001172 regenerating effect Effects 0.000 description 1
- 230000037425 regulation of transcription Effects 0.000 description 1
- 230000011506 response to oxidative stress Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 238000010839 reverse transcription Methods 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 230000006965 reversible inhibition Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 239000003161 ribonuclease inhibitor Substances 0.000 description 1
- 239000002336 ribonucleotide Substances 0.000 description 1
- 125000002652 ribonucleotide group Chemical group 0.000 description 1
- 229920006298 saran Polymers 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 150000003341 sedoheptuloses Chemical class 0.000 description 1
- 239000006152 selective media Substances 0.000 description 1
- 230000009919 sequestration Effects 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 108091006024 signal transducing proteins Proteins 0.000 description 1
- 102000034285 signal transducing proteins Human genes 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 230000003584 silencer Effects 0.000 description 1
- 238000001542 size-exclusion chromatography Methods 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- 101150066103 smg6 gene Proteins 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 210000001988 somatic stem cell Anatomy 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000037423 splicing regulation Effects 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 230000010473 stable expression Effects 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 229910021653 sulphate ion Inorganic materials 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 210000000225 synapse Anatomy 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 238000010809 targeting technique Methods 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
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
- 230000036964 tight binding Effects 0.000 description 1
- 230000005100 tissue tropism Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 239000012096 transfection reagent Substances 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 238000003146 transient transfection Methods 0.000 description 1
- 108091005703 transmembrane proteins Proteins 0.000 description 1
- 102000035160 transmembrane proteins Human genes 0.000 description 1
- 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 1
- GWBUNZLLLLDXMD-UHFFFAOYSA-H tricopper;dicarbonate;dihydroxide Chemical compound [OH-].[OH-].[Cu+2].[Cu+2].[Cu+2].[O-]C([O-])=O.[O-]C([O-])=O GWBUNZLLLLDXMD-UHFFFAOYSA-H 0.000 description 1
- 208000022679 triple-negative breast carcinoma Diseases 0.000 description 1
- 230000007306 turnover Effects 0.000 description 1
- 229910021642 ultra pure water Inorganic materials 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
- 238000005199 ultracentrifugation Methods 0.000 description 1
- 239000012498 ultrapure water Substances 0.000 description 1
- 210000001364 upper extremity Anatomy 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 125000005287 vanadyl group Chemical group 0.000 description 1
- UUUGYDOQQLOJQA-UHFFFAOYSA-L vanadyl sulfate Chemical compound [V+2]=O.[O-]S([O-])(=O)=O UUUGYDOQQLOJQA-UHFFFAOYSA-L 0.000 description 1
- 229940041260 vanadyl sulfate Drugs 0.000 description 1
- 229910000352 vanadyl sulfate Inorganic materials 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 230000029812 viral genome replication Effects 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 150000003742 xyloses Chemical class 0.000 description 1
- 210000005253 yeast cell Anatomy 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/16—Hydrolases (3) acting on ester bonds (3.1)
- C12N9/22—Ribonucleases [RNase]; Deoxyribonucleases [DNase]
-
- 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
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/111—General methods applicable to biologically active non-coding nucleic acids
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
- C07K2319/09—Fusion polypeptide containing a localisation/targetting motif containing a nuclear localisation signal
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/80—Fusion polypeptide containing a DNA binding domain, e.g. Lacl or Tet-repressor
-
- 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
-
- 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]
-
- 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)
- Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Chemical & Material Sciences (AREA)
- Biomedical Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Molecular Biology (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Biotechnology (AREA)
- General Health & Medical Sciences (AREA)
- General Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Medicinal Chemistry (AREA)
- Microbiology (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Physics & Mathematics (AREA)
- Biophysics (AREA)
- Plant Pathology (AREA)
- Epidemiology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Immunology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Neurology (AREA)
- Psychology (AREA)
- Neurosurgery (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201562259014P | 2015-11-23 | 2015-11-23 | |
| PCT/US2016/063429 WO2017091630A1 (en) | 2015-11-23 | 2016-11-22 | Tracking and manipulating cellular rna via nuclear delivery of crispr/cas9 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2930643T3 true ES2930643T3 (es) | 2022-12-20 |
Family
ID=57750540
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES16822766T Active ES2930643T3 (es) | 2015-11-23 | 2016-11-22 | Seguimiento y manipulación de ARN celular a través de la administración nuclear de CRISPR/CAS9 |
Country Status (10)
| Country | Link |
|---|---|
| US (4) | US20170145394A1 (enExample) |
| EP (2) | EP3380613B1 (enExample) |
| JP (2) | JP2019500899A (enExample) |
| CN (1) | CN109072235B (enExample) |
| AU (1) | AU2016359629B2 (enExample) |
| CA (1) | CA3005968A1 (enExample) |
| ES (1) | ES2930643T3 (enExample) |
| PT (1) | PT3380613T (enExample) |
| SG (2) | SG11201804372PA (enExample) |
| WO (1) | WO2017091630A1 (enExample) |
Families Citing this family (73)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10323236B2 (en) | 2011-07-22 | 2019-06-18 | President And Fellows Of Harvard College | Evaluation and improvement of nuclease cleavage specificity |
| US9163284B2 (en) | 2013-08-09 | 2015-10-20 | President And Fellows Of Harvard College | Methods for identifying a target site of a Cas9 nuclease |
| US9359599B2 (en) | 2013-08-22 | 2016-06-07 | President And Fellows Of Harvard College | Engineered transcription activator-like effector (TALE) domains and uses thereof |
| US9526784B2 (en) | 2013-09-06 | 2016-12-27 | President And Fellows Of Harvard College | Delivery system for functional nucleases |
| US9340799B2 (en) | 2013-09-06 | 2016-05-17 | President And Fellows Of Harvard College | MRNA-sensing switchable gRNAs |
| US9322037B2 (en) | 2013-09-06 | 2016-04-26 | President And Fellows Of Harvard College | Cas9-FokI fusion proteins and uses thereof |
| US11053481B2 (en) | 2013-12-12 | 2021-07-06 | President And Fellows Of Harvard College | Fusions of Cas9 domains and nucleic acid-editing domains |
| EP4079847A1 (en) | 2014-07-30 | 2022-10-26 | President And Fellows Of Harvard College | Cas9 proteins including ligand-dependent inteins |
| CA2990699A1 (en) | 2015-06-29 | 2017-01-05 | Ionis Pharmaceuticals, Inc. | Modified crispr rna and modified single crispr rna and uses thereof |
| IL294014B2 (en) | 2015-10-23 | 2024-07-01 | Harvard College | Nucleobase editors and uses thereof |
| EP3380613B1 (en) | 2015-11-23 | 2022-10-26 | The Regents of the University of California | Tracking and manipulating cellular rna via nuclear delivery of crispr/cas9 |
| WO2018027078A1 (en) | 2016-08-03 | 2018-02-08 | President And Fellows Of Harard College | Adenosine nucleobase editors and uses thereof |
| US11661590B2 (en) | 2016-08-09 | 2023-05-30 | President And Fellows Of Harvard College | Programmable CAS9-recombinase fusion proteins and uses thereof |
| US11542509B2 (en) | 2016-08-24 | 2023-01-03 | President And Fellows Of Harvard College | Incorporation of unnatural amino acids into proteins using base editing |
| SG11201903089RA (en) | 2016-10-14 | 2019-05-30 | Harvard College | Aav delivery of nucleobase editors |
| US10745677B2 (en) | 2016-12-23 | 2020-08-18 | President And Fellows Of Harvard College | Editing of CCR5 receptor gene to protect against HIV infection |
| EP3592381A1 (en) | 2017-03-09 | 2020-01-15 | President and Fellows of Harvard College | Cancer vaccine |
| EP3592853A1 (en) | 2017-03-09 | 2020-01-15 | President and Fellows of Harvard College | Suppression of pain by gene editing |
| CN110914310A (zh) | 2017-03-10 | 2020-03-24 | 哈佛大学的校长及成员们 | 胞嘧啶至鸟嘌呤碱基编辑器 |
| GB2575930A (en) | 2017-03-23 | 2020-01-29 | Harvard College | Nucleobase editors comprising nucleic acid programmable DNA binding proteins |
| WO2018208998A1 (en) | 2017-05-10 | 2018-11-15 | The Regents Of The University Of California | Directed editing of cellular rna via nuclear delivery of crispr/cas9 |
| WO2018209320A1 (en) | 2017-05-12 | 2018-11-15 | President And Fellows Of Harvard College | Aptazyme-embedded guide rnas for use with crispr-cas9 in genome editing and transcriptional activation |
| AU2018283405B2 (en) | 2017-06-15 | 2025-06-26 | The Regents Of The University Of California | Targeted non-viral DNA insertions |
| 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) |
| US10476825B2 (en) | 2017-08-22 | 2019-11-12 | Salk Institue for Biological Studies | RNA targeting methods and compositions |
| US11970720B2 (en) | 2017-08-22 | 2024-04-30 | Salk Institute For Biological Studies | RNA targeting methods and compositions |
| EP3676376B1 (en) | 2017-08-30 | 2025-01-15 | President and Fellows of Harvard College | High efficiency base editors comprising gam |
| WO2019079347A1 (en) | 2017-10-16 | 2019-04-25 | The Broad Institute, Inc. | USES OF BASIC EDITORS ADENOSINE |
| JP7381476B2 (ja) * | 2017-10-24 | 2023-11-15 | サンガモ セラピューティクス， インコーポレイテッド | 希少疾患の処置のための方法および組成物 |
| EP3700924A4 (en) | 2017-10-27 | 2021-11-03 | The Regents of the University of California | TARGETED REPLACEMENT OF ENDOGENOUS T-CELL RECEPTORS |
| CN107893260B (zh) * | 2017-11-27 | 2021-01-12 | 广州市锐博生物科技有限公司 | 高效去除核糖体rna的构建转录组测序文库的方法及试剂盒 |
| CN108103090B (zh) * | 2017-12-12 | 2021-06-15 | 中山大学附属第一医院 | 靶向RNA甲基化的RNA Cas9-m6A修饰载体系统及其构建方法和应用 |
| WO2019118949A1 (en) | 2017-12-15 | 2019-06-20 | The Broad Institute, Inc. | Systems and methods for predicting repair outcomes in genetic engineering |
| CN108559760A (zh) * | 2018-01-09 | 2018-09-21 | 陕西师范大学 | 基于CRISPR靶向基因组修饰技术建立荧光素酶knock-in细胞系的方法 |
| AU2019236210B2 (en) | 2018-03-14 | 2025-07-03 | Arbor Biotechnologies, Inc. | Novel CRISPR DNA targeting enzymes and systems |
| WO2019178428A1 (en) * | 2018-03-14 | 2019-09-19 | Arbor Biotechnologies, Inc. | Novel crispr dna and rna targeting enzymes and systems |
| EP3810273A4 (en) * | 2018-05-15 | 2022-03-16 | The Children's Hospital of Philadelphia | HTT ALLELE REMOVAL BASED ON CRISPR INTERFERENCE AND TREATMENT OF HUNTINGTON'S DISEASE |
| WO2019222555A1 (en) | 2018-05-16 | 2019-11-21 | Arbor Biotechnologies, Inc. | Novel crispr-associated systems and components |
| WO2019226953A1 (en) | 2018-05-23 | 2019-11-28 | The Broad Institute, Inc. | Base editors and uses thereof |
| EP3575401A1 (en) * | 2018-05-29 | 2019-12-04 | Ecole Polytechnique Federale De Lausanne (Epfl) | Methods of treating or preventing an aging-related disease |
| EP3801641A4 (en) * | 2018-06-08 | 2022-09-28 | Locanabio, Inc. | Compositions and methods for the modulation of adaptive immunity |
| CN112930395A (zh) * | 2018-06-08 | 2021-06-08 | 洛卡纳生物股份有限公司 | 靶向rna的融合蛋白组合物和使用方法 |
| CN112423781A (zh) * | 2018-07-13 | 2021-02-26 | 普林斯顿大学理事会 | 用于调节应激颗粒组装的系统和方法 |
| WO2020069331A1 (en) * | 2018-09-28 | 2020-04-02 | The Jackson Laboratory | Artificial rna-guided splicing factors |
| WO2020092453A1 (en) | 2018-10-29 | 2020-05-07 | The Broad Institute, Inc. | Nucleobase editors comprising geocas9 and uses thereof |
| CN109706149B (zh) * | 2018-11-29 | 2020-12-18 | 华中农业大学 | 一种改进的16S-seq方法及其应用 |
| RU2694396C1 (ru) * | 2018-12-14 | 2019-07-12 | Федеральное Бюджетное Учреждение Науки "Центральный Научно-Исследовательский Институт Эпидемиологии" Федеральной Службы По Надзору В Сфере Защиты Прав Потребителей И Благополучия Человека | РНК-проводник St10 для использования в высокоспецифической системе нуклеаз Streptococcus thermophilus CRISPR/Cas9 (StCas9) и применение указанного РНК-проводника и белка StCas9 для подавления экспрессии вируса гепатита B в клетке-хозяине и для элиминации вирусной ДНК из клетки-хозяина |
| AU2020208346A1 (en) * | 2019-01-14 | 2021-07-29 | University Of Rochester | Targeted nuclear RNA cleavage and polyadenylation with CRISPR-cas |
| US12351837B2 (en) | 2019-01-23 | 2025-07-08 | The Broad Institute, Inc. | Supernegatively charged proteins and uses thereof |
| WO2020160125A1 (en) * | 2019-01-29 | 2020-08-06 | Flagship Pioneering Innovations V, Inc. | Compositions comprising an endonuclease and methods for purifying an endonuclease |
| LU101118B1 (en) | 2019-02-06 | 2020-08-06 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH) | Method for detecting a specific splice event of a gene of interest |
| CN109811072B (zh) * | 2019-02-28 | 2022-05-06 | 广州微远医疗器械有限公司 | 用于结核分枝杆菌复合群的crispr检测引物组及其用途 |
| DE112020001342T5 (de) | 2019-03-19 | 2022-01-13 | President and Fellows of Harvard College | Verfahren und Zusammensetzungen zum Editing von Nukleotidsequenzen |
| CN110004181B (zh) * | 2019-03-20 | 2022-10-11 | 东北农业大学 | 一种附加型CRISPR/Cas9表达载体及其构建方法与应用 |
| WO2020198640A1 (en) * | 2019-03-27 | 2020-10-01 | Massachusetts Institute Of Technology | Programmable imaging methods and compositions |
| WO2020214842A1 (en) | 2019-04-17 | 2020-10-22 | The Broad Institute, Inc. | Adenine base editors with reduced off-target effects |
| US12139517B2 (en) | 2019-04-23 | 2024-11-12 | Sangamo Therapeutics, Inc. | Modulators of chromosome 9 open reading frame 72 gene expression and uses thereof |
| WO2021072328A1 (en) | 2019-10-10 | 2021-04-15 | The Broad Institute, Inc. | Methods and compositions for prime editing rna |
| CN110714008A (zh) * | 2019-10-17 | 2020-01-21 | 南通大学 | 核苷酸序列构建的crispr重组质粒靶向编辑iss序列的方法 |
| CA3163565A1 (en) * | 2019-12-02 | 2021-06-10 | Council Of Scientific & Industrial Research | Method and kit for detection of polynucleotide |
| GB2614813B (en) | 2020-05-08 | 2025-05-07 | Harvard College | Methods and compositions for simultaneous editing of both strands of a target double-stranded nucleotide sequence |
| US12139710B2 (en) | 2020-10-28 | 2024-11-12 | The Regents Of The University Of California | Methods of modulating RNA translation |
| GB202105455D0 (en) | 2021-04-16 | 2021-06-02 | Ucl Business Ltd | Composition |
| EP4095243A1 (en) * | 2021-05-25 | 2022-11-30 | European Molecular Biology Laboratory | System for hybridization-based precision genome cleavage and editing, and uses thereof |
| WO2023023584A2 (en) | 2021-08-19 | 2023-02-23 | Eclipse Bioinnovations, Inc. | Methods for detecting rna binding protein complexes |
| AU2022337146A1 (en) | 2021-09-03 | 2024-03-14 | Tacit Therapeutics, Inc. | Rna editing via recruitment of spliceosome components |
| CR20240195A (es) | 2021-10-14 | 2024-06-20 | Arsenal Biosciences Inc | Células inmunitarias que tienen arnhc coexpresados y sistemas de compuerta lógica |
| WO2023129973A2 (en) * | 2021-12-30 | 2023-07-06 | Eclipse Bioinnovations, Inc. | Methods for detecting rna modification targets on a gene |
| WO2023205637A1 (en) * | 2022-04-18 | 2023-10-26 | Locanabio, Inc. | Rna-targeting compositions and methods for treating c9/orf72 diseases |
| CN115044620B (zh) * | 2022-06-30 | 2024-01-05 | 上海海洋大学 | 微卫星重复序列敲除突变体的构建方法和应用 |
| CN115927425B (zh) * | 2022-07-14 | 2025-03-25 | 华中农业大学 | 一种嗜热栖热菌基因编辑质粒及在生产超氧化物歧化酶中的应用 |
| AU2024270764A1 (en) | 2023-05-15 | 2025-12-04 | Nchroma Bio, Inc. | Compositions and methods for epigenetic regulation of hbv gene expression |
| CN117925787A (zh) * | 2024-01-17 | 2024-04-26 | 北京医院 | 基于“内-外”双重信号放大的DCasFISH染色体多色原位成像系统 |
Family Cites Families (92)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3687808A (en) | 1969-08-14 | 1972-08-29 | Univ Leland Stanford Junior | Synthetic polynucleotides |
| US5034506A (en) | 1985-03-15 | 1991-07-23 | Anti-Gene Development Group | Uncharged morpholino-based polymers having achiral intersubunit linkages |
| US5185444A (en) | 1985-03-15 | 1993-02-09 | Anti-Gene Deveopment Group | Uncharged morpolino-based polymers having phosphorous containing chiral intersubunit linkages |
| US5166315A (en) | 1989-12-20 | 1992-11-24 | Anti-Gene Development Group | Sequence-specific binding polymers for duplex nucleic acids |
| US5405938A (en) | 1989-12-20 | 1995-04-11 | Anti-Gene Development Group | Sequence-specific binding polymers for duplex nucleic acids |
| US5235033A (en) | 1985-03-15 | 1993-08-10 | Anti-Gene Development Group | Alpha-morpholino ribonucleoside derivatives and polymers thereof |
| US5216141A (en) | 1988-06-06 | 1993-06-01 | Benner Steven A | Oligonucleotide analogs containing sulfur linkages |
| US5264562A (en) | 1989-10-24 | 1993-11-23 | Gilead Sciences, Inc. | Oligonucleotide analogs with novel linkages |
| US5264564A (en) | 1989-10-24 | 1993-11-23 | Gilead Sciences | Oligonucleotide analogs with novel linkages |
| US5470967A (en) | 1990-04-10 | 1995-11-28 | The Dupont Merck Pharmaceutical Company | Oligonucleotide analogs with sulfamate linkages |
| US5618704A (en) | 1990-07-27 | 1997-04-08 | Isis Pharmacueticals, Inc. | Backbone-modified oligonucleotide analogs and preparation thereof through radical coupling |
| US5541307A (en) | 1990-07-27 | 1996-07-30 | Isis Pharmaceuticals, Inc. | Backbone modified oligonucleotide analogs and solid phase synthesis thereof |
| US5677437A (en) | 1990-07-27 | 1997-10-14 | Isis Pharmaceuticals, Inc. | Heteroatomic oligonucleoside linkages |
| US5608046A (en) | 1990-07-27 | 1997-03-04 | Isis Pharmaceuticals, Inc. | Conjugated 4'-desmethyl nucleoside analog compounds |
| US5602240A (en) | 1990-07-27 | 1997-02-11 | Ciba Geigy Ag. | Backbone modified oligonucleotide analogs |
| US5489677A (en) | 1990-07-27 | 1996-02-06 | Isis Pharmaceuticals, Inc. | Oligonucleoside linkages containing adjacent oxygen and nitrogen atoms |
| US5623070A (en) | 1990-07-27 | 1997-04-22 | Isis Pharmaceuticals, Inc. | Heteroatomic oligonucleoside linkages |
| US5610289A (en) | 1990-07-27 | 1997-03-11 | Isis Pharmaceuticals, Inc. | Backbone modified oligonucleotide analogues |
| NZ239247A (en) | 1990-08-03 | 1993-11-25 | Sterling Drug Inc | Oligonucleosides containing a non-phosphate inter nucleoside linkage |
| US5214134A (en) | 1990-09-12 | 1993-05-25 | Sterling Winthrop Inc. | Process of linking nucleosides with a siloxane bridge |
| US5561225A (en) | 1990-09-19 | 1996-10-01 | Southern Research Institute | Polynucleotide analogs containing sulfonate and sulfonamide internucleoside linkages |
| WO1992005186A1 (en) | 1990-09-20 | 1992-04-02 | Gilead Sciences | Modified internucleoside linkages |
| US5714331A (en) | 1991-05-24 | 1998-02-03 | Buchardt, Deceased; Ole | Peptide nucleic acids having enhanced binding affinity, sequence specificity and solubility |
| US5719262A (en) | 1993-11-22 | 1998-02-17 | Buchardt, Deceased; Ole | Peptide nucleic acids having amino acid side chains |
| US5539082A (en) | 1993-04-26 | 1996-07-23 | Nielsen; Peter E. | Peptide nucleic acids |
| US5633360A (en) | 1992-04-14 | 1997-05-27 | Gilead Sciences, Inc. | Oligonucleotide analogs capable of passive cell membrane permeation |
| US5434257A (en) | 1992-06-01 | 1995-07-18 | Gilead Sciences, Inc. | Binding compentent oligomers containing unsaturated 3',5' and 2',5' linkages |
| GB9304618D0 (en) | 1993-03-06 | 1993-04-21 | Ciba Geigy Ag | Chemical compounds |
| DE69407032T2 (de) | 1993-03-31 | 1998-07-02 | Sanofi Sa | Oligonucleotide mit amidverkettungen die phosphoesterverkettungen einsetzen |
| DE19502912A1 (de) | 1995-01-31 | 1996-08-01 | Hoechst Ag | G-Cap Stabilisierte Oligonucleotide |
| US6042820A (en) | 1996-12-20 | 2000-03-28 | Connaught Laboratories Limited | Biodegradable copolymer containing α-hydroxy acid and α-amino acid units |
| JP3756313B2 (ja) | 1997-03-07 | 2006-03-15 | 武 今西 | 新規ビシクロヌクレオシド及びオリゴヌクレオチド類縁体 |
| ATE293123T1 (de) | 1997-09-12 | 2005-04-15 | Exiqon As | Bi- und tri-zyklische - nukleosid, nukleotid und oligonukleotid-analoga |
| DE69940196D1 (de) | 1998-04-15 | 2009-02-12 | Hutchinson Fred Cancer Res | Methoden und vektorenkonstrukte zur erzeugung von transgene nagetieren, welche ein heterologes gen ubiquitär exprimieren |
| US6472375B1 (en) | 1998-04-16 | 2002-10-29 | John Wayne Cancer Institute | DNA vaccine and methods for its use |
| US7078387B1 (en) | 1998-12-28 | 2006-07-18 | Arch Development Corp. | Efficient and stable in vivo gene transfer to cardiomyocytes using recombinant adeno-associated virus vectors |
| ATE356824T1 (de) | 1999-05-04 | 2007-04-15 | Santaris Pharma As | L-ribo-lna analoge |
| WO2001048190A2 (en) | 1999-12-23 | 2001-07-05 | Exiqon A/S | Therapeutic uses of lna-modified oligonucleotides |
| WO2001075097A2 (en) | 2000-03-31 | 2001-10-11 | Cambridge Antibody Technology Limited | Improvements to ribosome display |
| US8592569B2 (en) | 2007-11-22 | 2013-11-26 | Japan Science And Technology Agency | Small RNA-dependent translational regulatory system in cell or artificial cell model |
| US9580714B2 (en) | 2010-11-24 | 2017-02-28 | The University Of Western Australia | Peptides for the specific binding of RNA targets |
| CN106626106A (zh) | 2011-01-07 | 2017-05-10 | 坂东机工株式会社 | 用于刻划碳化硅板的方法和设备 |
| JP6164488B2 (ja) | 2011-10-21 | 2017-07-19 | 国立大学法人九州大学 | Ｐｐｒモチーフを利用したｒｎａ結合性蛋白質の設計方法及びその利用 |
| EP3858847A1 (en) * | 2011-11-30 | 2021-08-04 | Sarepta Therapeutics, Inc. | Oligonucleotides for treating expanded repeat diseases |
| WO2013130683A2 (en) | 2012-02-27 | 2013-09-06 | Amunix Operating Inc. | Xten conjugate compositions and methods of making same |
| CN105209621B (zh) * | 2012-12-12 | 2021-05-25 | 布罗德研究所有限公司 | 对用于序列操纵的改进的系统、方法和酶组合物进行的工程化和优化 |
| AU2013359199C1 (en) | 2012-12-12 | 2021-06-17 | Massachusetts Institute Of Technology | Delivery, engineering and optimization of systems, methods and compositions for sequence manipulation and therapeutic applications |
| US8697359B1 (en) | 2012-12-12 | 2014-04-15 | The Broad Institute, Inc. | CRISPR-Cas systems and methods for altering expression of gene products |
| AU2014207618A1 (en) * | 2013-01-16 | 2015-08-06 | Emory University | Cas9-nucleic acid complexes and uses related thereto |
| TWI484033B (zh) | 2013-01-25 | 2015-05-11 | Univ China Medical | 培養幹細胞之方法及套組 |
| WO2014186585A2 (en) * | 2013-05-15 | 2014-11-20 | Sangamo Biosciences, Inc. | Methods and compositions for treatment of a genetic condition |
| US11685935B2 (en) * | 2013-05-29 | 2023-06-27 | Cellectis | Compact scaffold of Cas9 in the type II CRISPR system |
| JP7065564B2 (ja) * | 2013-05-29 | 2022-05-12 | セレクティス | Ｃａｓ９ニッカーゼ活性を用いて正確なｄｎａ切断をもたらすための方法 |
| CN105517579B (zh) * | 2013-07-10 | 2019-11-15 | 哈佛大学校长及研究员协会 | 用于RNA向导的基因调节和编辑的正交Cas9蛋白 |
| MX2016002044A (es) | 2013-08-16 | 2016-08-17 | Rana Therapeutics Inc | Composiciones y metodos para modular el acido ribonucleico. |
| US9322037B2 (en) | 2013-09-06 | 2016-04-26 | President And Fellows Of Harvard College | Cas9-FokI fusion proteins and uses thereof |
| US10822606B2 (en) * | 2013-09-27 | 2020-11-03 | The Regents Of The University Of California | Optimized small guide RNAs and methods of use |
| US9074199B1 (en) | 2013-11-19 | 2015-07-07 | President And Fellows Of Harvard College | Mutant Cas9 proteins |
| US11053481B2 (en) | 2013-12-12 | 2021-07-06 | President And Fellows Of Harvard College | Fusions of Cas9 domains and nucleic acid-editing domains |
| US9994831B2 (en) | 2013-12-12 | 2018-06-12 | The Regents Of The University Of California | Methods and compositions for modifying a single stranded target nucleic acid |
| AU2014362245A1 (en) * | 2013-12-12 | 2016-06-16 | Massachusetts Institute Of Technology | Compositions and methods of use of CRISPR-Cas systems in nucleotide repeat disorders |
| CN106459957B (zh) | 2014-03-05 | 2020-03-20 | 国立大学法人神户大学 | 用于特异性转变靶向dna序列的核酸碱基的基因组序列的修饰方法、及其使用的分子复合体 |
| CN105338513B (zh) | 2014-08-08 | 2019-12-10 | 中兴通讯股份有限公司 | 设备到设备业务处理方法及装置 |
| RU2711506C2 (ru) | 2014-12-17 | 2020-01-17 | ПРОКЬЮЭР ТЕРАПЬЮТИКС II Би.Ви. | Редактирование целевой рнк |
| WO2016106236A1 (en) * | 2014-12-23 | 2016-06-30 | The Broad Institute Inc. | Rna-targeting system |
| US10330674B2 (en) | 2015-01-13 | 2019-06-25 | Massachusetts Institute Of Technology | Pumilio domain-based modular protein architecture for RNA binding |
| US10920221B2 (en) | 2015-05-13 | 2021-02-16 | President And Fellows Of Harvard College | Methods of making and using guide RNA for use with Cas9 systems |
| WO2016191684A1 (en) | 2015-05-28 | 2016-12-01 | Finer Mitchell H | Genome editing vectors |
| EP3303634B1 (en) | 2015-06-03 | 2023-08-30 | The Regents of The University of California | Cas9 variants and methods of use thereof |
| EP3334823B1 (en) | 2015-06-05 | 2024-05-22 | The Regents of The University of California | Method and kit for generating crispr/cas guide rnas |
| US20160362667A1 (en) | 2015-06-10 | 2016-12-15 | Caribou Biosciences, Inc. | CRISPR-Cas Compositions and Methods |
| WO2016201138A1 (en) | 2015-06-12 | 2016-12-15 | The Regents Of The University Of California | Reporter cas9 variants and methods of use thereof |
| EP3323890A4 (en) | 2015-07-14 | 2019-01-30 | Fukuoka University | METHOD OF INDUSTRYING SITE-SPECIFIC RNA MUTATIONS, TARGETED EDITING GUIDE RNA USED IN THE METHOD AND TARGET RNA TARGET EDITING GUIDE RNA COMPLEX |
| PT4140491T (pt) | 2015-09-21 | 2023-12-05 | Trilink Biotechnologies Llc | Métolo para a sintetização de arn capeados em 5 |
| WO2017053312A1 (en) | 2015-09-21 | 2017-03-30 | The Regents Of The University Of California | Compositions and methods for target nucleic acid modification |
| EP3380613B1 (en) * | 2015-11-23 | 2022-10-26 | The Regents of the University of California | Tracking and manipulating cellular rna via nuclear delivery of crispr/cas9 |
| AU2017283713B2 (en) | 2016-06-17 | 2021-04-08 | Massachusetts Institute Of Technology | Type VI CRISPR orthologs and systems |
| LT6525B (lt) | 2016-06-29 | 2018-05-10 | Uab Pixpro | Skaitmeninių vaizdų skyros didinimo būdas taikant unikalų dalinai persidengiančių mažos skyros vaizdų apdorojimą |
| WO2018027078A1 (en) | 2016-08-03 | 2018-02-08 | President And Fellows Of Harard College | Adenosine nucleobase editors and uses thereof |
| CN119351474A (zh) | 2017-02-22 | 2025-01-24 | 克里斯珀医疗股份公司 | 用于基因编辑的组合物和方法 |
| WO2018183703A1 (en) | 2017-03-31 | 2018-10-04 | NeuroDiagnostics LLC | Lymphocyte-based morphometric test for alzheimer's disease |
| WO2018208998A1 (en) | 2017-05-10 | 2018-11-15 | The Regents Of The University Of California | Directed editing of cellular rna via nuclear delivery of crispr/cas9 |
| US10392616B2 (en) | 2017-06-30 | 2019-08-27 | Arbor Biotechnologies, Inc. | CRISPR RNA targeting enzymes and systems and uses thereof |
| US10476825B2 (en) | 2017-08-22 | 2019-11-12 | Salk Institue for Biological Studies | RNA targeting methods and compositions |
| JP2020535802A (ja) | 2017-09-21 | 2020-12-10 | ザ・ブロード・インスティテュート・インコーポレイテッド | 標的化核酸編集のための系、方法、及び組成物 |
| CN108103090B (zh) | 2017-12-12 | 2021-06-15 | 中山大学附属第一医院 | 靶向RNA甲基化的RNA Cas9-m6A修饰载体系统及其构建方法和应用 |
| EP3728588A4 (en) | 2017-12-22 | 2022-03-09 | The Broad Institute, Inc. | CAS12A SYSTEMS, METHODS AND COMPOSITIONS FOR TARGETED EDIT OF RNA BASES |
| CN112513250A (zh) | 2018-04-20 | 2021-03-16 | 加利福尼亚大学董事会 | 用于跟踪和操纵细胞rna的融合蛋白和融合核糖核酸 |
| US20210332344A1 (en) | 2018-08-31 | 2021-10-28 | The Regents Of The University Of California | Directed modification of rna |
| WO2020047489A1 (en) | 2018-08-31 | 2020-03-05 | The Regents Of The University Of California | Directed pseudouridylation of rna |
| CN110055284A (zh) | 2019-04-15 | 2019-07-26 | 中山大学 | 一种基于PspCas13b-Alkbh5单基因特异性m6A修饰编辑方法 |
| WO2020214806A1 (en) | 2019-04-16 | 2020-10-22 | The Regents Of The University Of California | Protein translational control |
-
2016
- 2016-11-22 EP EP16822766.8A patent/EP3380613B1/en active Active
- 2016-11-22 SG SG11201804372PA patent/SG11201804372PA/en unknown
- 2016-11-22 SG SG10202004557QA patent/SG10202004557QA/en unknown
- 2016-11-22 EP EP22195456.3A patent/EP4163374A1/en active Pending
- 2016-11-22 ES ES16822766T patent/ES2930643T3/es active Active
- 2016-11-22 JP JP2018545579A patent/JP2019500899A/ja active Pending
- 2016-11-22 US US15/359,567 patent/US20170145394A1/en not_active Abandoned
- 2016-11-22 CA CA3005968A patent/CA3005968A1/en active Pending
- 2016-11-22 AU AU2016359629A patent/AU2016359629B2/en active Active
- 2016-11-22 CN CN201680079817.XA patent/CN109072235B/zh active Active
- 2016-11-22 WO PCT/US2016/063429 patent/WO2017091630A1/en not_active Ceased
- 2016-11-22 PT PT168227668T patent/PT3380613T/pt unknown
-
2018
- 2018-08-03 US US16/054,298 patent/US20190040370A1/en not_active Abandoned
-
2020
- 2020-02-19 US US16/794,918 patent/US11667903B2/en active Active
-
2022
- 2022-02-18 JP JP2022023996A patent/JP2022081503A/ja active Pending
-
2023
- 2023-04-25 US US18/306,673 patent/US20230365951A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| US20200239863A1 (en) | 2020-07-30 |
| US11667903B2 (en) | 2023-06-06 |
| CA3005968A1 (en) | 2017-06-01 |
| PT3380613T (pt) | 2022-12-02 |
| EP3380613B1 (en) | 2022-10-26 |
| WO2017091630A4 (en) | 2017-08-24 |
| CN109072235B (zh) | 2023-02-28 |
| AU2016359629B2 (en) | 2023-03-09 |
| US20170145394A1 (en) | 2017-05-25 |
| JP2022081503A (ja) | 2022-05-31 |
| WO2017091630A1 (en) | 2017-06-01 |
| SG11201804372PA (en) | 2018-06-28 |
| CN109072235A (zh) | 2018-12-21 |
| US20190040370A1 (en) | 2019-02-07 |
| US20230365951A1 (en) | 2023-11-16 |
| JP2019500899A (ja) | 2019-01-17 |
| AU2016359629A1 (en) | 2018-06-07 |
| EP4163374A1 (en) | 2023-04-12 |
| EP3380613A1 (en) | 2018-10-03 |
| SG10202004557QA (en) | 2020-06-29 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2930643T3 (es) | Seguimiento y manipulación de ARN celular a través de la administración nuclear de CRISPR/CAS9 | |
| JP7379447B2 (ja) | ゲノム編集分子の細胞内送達のためのペプチドおよびナノ粒子 | |
| CN110418647B (zh) | Rna指导的核酸修饰酶及其使用方法 | |
| JP7093728B2 (ja) | 化学的に修飾されたガイドｒｎａを使用する高特異性ゲノム編集 | |
| JP2023027277A (ja) | Ｒｎａ誘導型核酸修飾酵素及びその使用方法 | |
| ES2962509T3 (es) | Métodos y composiciones para modificar ADN genómico | |
| CN117487776A (zh) | Casz组合物和使用方法 | |
| EP3405570A1 (en) | Crystal structure of crispr cpf1 | |
| CA3026112A1 (en) | Cpf1 complexes with reduced indel activity | |
| CA3026055A1 (en) | Novel crispr enzymes and systems | |
| KR20190089175A (ko) | 표적 핵산 변형을 위한 조성물 및 방법 | |
| TW202421205A (zh) | 基因編輯組分、系統及使用方法 | |
| JP2022514567A (ja) | ヌクレアーゼ媒介リピート伸長 | |
| WO2023137233A2 (en) | Compositions and methods for editing genomes | |
| HK1261890B (en) | Tracking and manipulating cellular rna via nuclear delivery of crispr/cas9 | |
| HK1261890A1 (en) | Tracking and manipulating cellular rna via nuclear delivery of crispr/cas9 | |
| Carufe | Applying Gene Editing Technology for Correction of Human Disease | |
| JP2025540708A (ja) | 遺伝子を修飾するエンドヌクレアーゼ | |
| CN120641122A (zh) | 基因修饰核酸内切酶 | |
| HK40012328A (en) | Rna-guided nucleic acid modifying enzymes and methods of use thereof |