JP2005532815A - 皮膚疾患の修正のためのスプライセオソームにより媒介されるｒｎａトランススプライシング - Google Patents
皮膚疾患の修正のためのスプライセオソームにより媒介されるｒｎａトランススプライシング Download PDFInfo
- Publication number
- JP2005532815A JP2005532815A JP2004521968A JP2004521968A JP2005532815A JP 2005532815 A JP2005532815 A JP 2005532815A JP 2004521968 A JP2004521968 A JP 2004521968A JP 2004521968 A JP2004521968 A JP 2004521968A JP 2005532815 A JP2005532815 A JP 2005532815A
- Authority
- JP
- Japan
- Prior art keywords
- nucleic acid
- acid molecule
- mrna
- cell
- target
- 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.)
- Withdrawn
Links
- 230000001404 mediated effect Effects 0.000 title claims abstract description 15
- 208000017520 skin disease Diseases 0.000 title abstract description 21
- 238000012937 correction Methods 0.000 title abstract description 14
- 210000001324 spliceosome Anatomy 0.000 title abstract description 11
- 210000004027 cell Anatomy 0.000 claims abstract description 178
- 108020004999 messenger RNA Proteins 0.000 claims abstract description 154
- 102000039446 nucleic acids Human genes 0.000 claims abstract description 126
- 108020004707 nucleic acids Proteins 0.000 claims abstract description 126
- 150000007523 nucleic acids Chemical class 0.000 claims abstract description 126
- 210000004927 skin cell Anatomy 0.000 claims abstract description 87
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 74
- 238000000034 method Methods 0.000 claims abstract description 55
- 239000013598 vector Substances 0.000 claims abstract description 46
- 239000000203 mixture Substances 0.000 claims abstract description 31
- 210000003491 skin Anatomy 0.000 claims abstract description 29
- 108091092236 Chimeric RNA Proteins 0.000 claims abstract description 24
- 230000009395 genetic defect Effects 0.000 claims abstract description 16
- 108010044493 collagen type XVII Proteins 0.000 claims abstract description 14
- 208000000453 Skin Neoplasms Diseases 0.000 claims abstract description 5
- 201000000849 skin cancer Diseases 0.000 claims abstract description 5
- 230000027455 binding Effects 0.000 claims description 122
- 239000002773 nucleotide Substances 0.000 claims description 57
- 125000003729 nucleotide group Chemical group 0.000 claims description 57
- 108020005067 RNA Splice Sites Proteins 0.000 claims description 56
- 210000002510 keratinocyte Anatomy 0.000 claims description 53
- 108010054050 Plectin Proteins 0.000 claims description 32
- 125000006850 spacer group Chemical group 0.000 claims description 30
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 27
- 230000014509 gene expression Effects 0.000 claims description 26
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 25
- 102000056300 Plectins Human genes 0.000 claims description 24
- 230000000295 complement effect Effects 0.000 claims description 18
- 230000015572 biosynthetic process Effects 0.000 claims description 14
- 239000013604 expression vector Substances 0.000 claims description 14
- 238000004519 manufacturing process Methods 0.000 claims description 10
- 108010017377 Collagen Type VII Proteins 0.000 claims description 9
- 102000004510 Collagen Type VII Human genes 0.000 claims description 9
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 7
- 230000003834 intracellular effect Effects 0.000 claims description 6
- 210000002752 melanocyte Anatomy 0.000 claims description 6
- 239000013603 viral vector Substances 0.000 claims description 5
- 108010085895 Laminin Proteins 0.000 claims description 4
- 230000002500 effect on skin Effects 0.000 claims description 4
- 230000003993 interaction Effects 0.000 claims description 4
- 206010028980 Neoplasm Diseases 0.000 claims description 3
- 201000011510 cancer Diseases 0.000 claims description 3
- 238000003384 imaging method Methods 0.000 claims description 3
- 229920001184 polypeptide Polymers 0.000 claims 23
- 210000003527 eukaryotic cell Anatomy 0.000 claims 3
- 208000005440 Basal Cell Neoplasms Diseases 0.000 claims 2
- 206010004146 Basal cell carcinoma Diseases 0.000 claims 2
- 201000001441 melanoma Diseases 0.000 claims 2
- 231100000331 toxic Toxicity 0.000 claims 2
- 230000002588 toxic effect Effects 0.000 claims 2
- 210000004881 tumor cell Anatomy 0.000 claims 2
- 108091032973 (ribonucleotides)n+m Proteins 0.000 abstract description 68
- 238000006243 chemical reaction Methods 0.000 abstract description 42
- 102000004169 proteins and genes Human genes 0.000 abstract description 40
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 16
- 201000010099 disease Diseases 0.000 abstract description 14
- 230000004481 post-translational protein modification Effects 0.000 abstract description 14
- 238000001415 gene therapy Methods 0.000 abstract description 12
- 208000025309 Hair disease Diseases 0.000 abstract description 4
- 208000012641 Pigmentation disease Diseases 0.000 abstract description 4
- 208000034653 disorder of pilosebaceous unit Diseases 0.000 abstract description 4
- 208000029443 keratinization disease Diseases 0.000 abstract description 4
- 239000002243 precursor Substances 0.000 abstract description 4
- 238000010353 genetic engineering Methods 0.000 abstract description 3
- 108010005774 beta-Galactosidase Proteins 0.000 description 61
- WQZGKKKJIJFFOK-FPRJBGLDSA-N beta-D-galactose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-FPRJBGLDSA-N 0.000 description 53
- 239000000047 product Substances 0.000 description 47
- 238000001890 transfection Methods 0.000 description 38
- 230000000694 effects Effects 0.000 description 37
- 238000003757 reverse transcription PCR Methods 0.000 description 37
- 239000012634 fragment Substances 0.000 description 34
- 230000035772 mutation Effects 0.000 description 31
- 108010035532 Collagen Proteins 0.000 description 29
- 108020004414 DNA Proteins 0.000 description 27
- 230000008439 repair process Effects 0.000 description 27
- 102000008186 Collagen Human genes 0.000 description 22
- 229920001436 collagen Polymers 0.000 description 22
- 239000002299 complementary DNA Substances 0.000 description 22
- 101150051118 PTM1 gene Proteins 0.000 description 20
- 108700024394 Exon Proteins 0.000 description 19
- 101150066555 lacZ gene Proteins 0.000 description 19
- 230000002950 deficient Effects 0.000 description 16
- 238000002474 experimental method Methods 0.000 description 15
- 230000004048 modification Effects 0.000 description 14
- 238000012986 modification Methods 0.000 description 14
- 239000013612 plasmid Substances 0.000 description 14
- 238000012761 co-transfection Methods 0.000 description 13
- 238000000338 in vitro Methods 0.000 description 13
- 108020004705 Codon Proteins 0.000 description 12
- 239000002585 base Substances 0.000 description 11
- 238000013518 transcription Methods 0.000 description 11
- 230000035897 transcription Effects 0.000 description 11
- 108091026890 Coding region Proteins 0.000 description 10
- 102100028256 Collagen alpha-1(XVII) chain Human genes 0.000 description 10
- 239000003153 chemical reaction reagent Substances 0.000 description 10
- 239000002609 medium Substances 0.000 description 10
- 238000012163 sequencing technique Methods 0.000 description 10
- 101150051160 COL17A1 gene Proteins 0.000 description 9
- 206010014989 Epidermolysis bullosa Diseases 0.000 description 9
- 238000003556 assay Methods 0.000 description 9
- 238000010276 construction Methods 0.000 description 9
- 238000010839 reverse transcription Methods 0.000 description 9
- 108090000994 Catalytic RNA Proteins 0.000 description 8
- 102000053642 Catalytic RNA Human genes 0.000 description 8
- 238000010240 RT-PCR analysis Methods 0.000 description 8
- 239000003795 chemical substances by application Substances 0.000 description 8
- 238000010586 diagram Methods 0.000 description 8
- 238000001476 gene delivery Methods 0.000 description 8
- 108091092562 ribozyme Proteins 0.000 description 8
- 238000006467 substitution reaction Methods 0.000 description 8
- 108091035707 Consensus sequence Proteins 0.000 description 7
- 101000860679 Homo sapiens Collagen alpha-1(XVII) chain Proteins 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 7
- 230000029087 digestion Effects 0.000 description 7
- 210000001519 tissue Anatomy 0.000 description 7
- -1 Sambrook et al. Chemical class 0.000 description 6
- 238000013459 approach Methods 0.000 description 6
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 6
- 238000005516 engineering process Methods 0.000 description 6
- 238000009396 hybridization Methods 0.000 description 6
- 238000010166 immunofluorescence Methods 0.000 description 6
- 238000001727 in vivo Methods 0.000 description 6
- 230000001965 increasing effect Effects 0.000 description 6
- 239000002953 phosphate buffered saline Substances 0.000 description 6
- 230000002829 reductive effect Effects 0.000 description 6
- 230000002441 reversible effect Effects 0.000 description 6
- 238000010186 staining Methods 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 102100026189 Beta-galactosidase Human genes 0.000 description 5
- 102000004190 Enzymes Human genes 0.000 description 5
- 108090000790 Enzymes Proteins 0.000 description 5
- 108091028043 Nucleic acid sequence Proteins 0.000 description 5
- 201000004681 Psoriasis Diseases 0.000 description 5
- 230000000692 anti-sense effect Effects 0.000 description 5
- 239000000872 buffer Substances 0.000 description 5
- 238000003776 cleavage reaction Methods 0.000 description 5
- 238000010367 cloning Methods 0.000 description 5
- 238000001514 detection method Methods 0.000 description 5
- 210000002615 epidermis Anatomy 0.000 description 5
- 210000002950 fibroblast Anatomy 0.000 description 5
- 238000003780 insertion Methods 0.000 description 5
- 230000037431 insertion Effects 0.000 description 5
- 208000008106 junctional epidermolysis bullosa Diseases 0.000 description 5
- 230000007246 mechanism Effects 0.000 description 5
- 239000008194 pharmaceutical composition Substances 0.000 description 5
- 238000011084 recovery Methods 0.000 description 5
- 230000001105 regulatory effect Effects 0.000 description 5
- 230000007017 scission Effects 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- 241000701161 unidentified adenovirus Species 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 101150056204 COL7A1 gene Proteins 0.000 description 4
- 101710082950 Collagen alpha-1(XVII) chain Proteins 0.000 description 4
- 101100496573 Homo sapiens COL7A1 gene Proteins 0.000 description 4
- 208000026350 Inborn Genetic disease Diseases 0.000 description 4
- 101710163270 Nuclease Proteins 0.000 description 4
- 108091034117 Oligonucleotide Proteins 0.000 description 4
- 102000015097 RNA Splicing Factors Human genes 0.000 description 4
- 108010039259 RNA Splicing Factors Proteins 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical group O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 4
- 230000003321 amplification Effects 0.000 description 4
- 238000004113 cell culture Methods 0.000 description 4
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 4
- 238000013461 design Methods 0.000 description 4
- 230000006870 function Effects 0.000 description 4
- 208000016361 genetic disease Diseases 0.000 description 4
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 4
- 230000001976 improved effect Effects 0.000 description 4
- 239000003550 marker Substances 0.000 description 4
- 239000012528 membrane Substances 0.000 description 4
- 238000003199 nucleic acid amplification method Methods 0.000 description 4
- 210000000056 organ Anatomy 0.000 description 4
- 230000004853 protein function Effects 0.000 description 4
- 230000006798 recombination Effects 0.000 description 4
- 238000005215 recombination Methods 0.000 description 4
- 230000001177 retroviral effect Effects 0.000 description 4
- 238000012552 review Methods 0.000 description 4
- 230000032258 transport Effects 0.000 description 4
- 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 3
- 108700028369 Alleles Proteins 0.000 description 3
- 241000702421 Dependoparvovirus Species 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 108700028146 Genetic Enhancer Elements Proteins 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 108091093037 Peptide nucleic acid Proteins 0.000 description 3
- 108010002747 Pfu DNA polymerase Proteins 0.000 description 3
- 238000012300 Sequence Analysis Methods 0.000 description 3
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 3
- 108700019146 Transgenes Proteins 0.000 description 3
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Chemical class Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 3
- 210000004207 dermis Anatomy 0.000 description 3
- 238000004520 electroporation Methods 0.000 description 3
- 239000003623 enhancer Substances 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- 230000002068 genetic effect Effects 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 210000004379 membrane Anatomy 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 239000011859 microparticle Substances 0.000 description 3
- 210000004940 nucleus Anatomy 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 239000000523 sample Substances 0.000 description 3
- 241001430294 unidentified retrovirus Species 0.000 description 3
- 238000011144 upstream manufacturing Methods 0.000 description 3
- 238000001262 western blot Methods 0.000 description 3
- CZMRCDWAGMRECN-UHFFFAOYSA-N 2-{[3,4-dihydroxy-2,5-bis(hydroxymethyl)oxolan-2-yl]oxy}-6-(hydroxymethyl)oxane-3,4,5-triol Chemical compound OCC1OC(CO)(OC2OC(CO)C(O)C(O)C2O)C(O)C1O CZMRCDWAGMRECN-UHFFFAOYSA-N 0.000 description 2
- PEHVGBZKEYRQSX-UHFFFAOYSA-N 7-deaza-adenine Chemical compound NC1=NC=NC2=C1C=CN2 PEHVGBZKEYRQSX-UHFFFAOYSA-N 0.000 description 2
- 101710085033 Beta-galactosidase LacZ Proteins 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 238000012270 DNA recombination Methods 0.000 description 2
- 238000001712 DNA sequencing Methods 0.000 description 2
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 2
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 2
- 108010008532 Deoxyribonuclease I Proteins 0.000 description 2
- 102100030012 Deoxyribonuclease-1 Human genes 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 101000938351 Homo sapiens Ephrin type-A receptor 3 Proteins 0.000 description 2
- 101100540311 Human papillomavirus type 16 E6 gene Proteins 0.000 description 2
- XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 description 2
- 102100034343 Integrase Human genes 0.000 description 2
- 108091092195 Intron Proteins 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- 238000000636 Northern blotting Methods 0.000 description 2
- 108010077850 Nuclear Localization Signals Proteins 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- 239000013614 RNA sample Substances 0.000 description 2
- 230000006819 RNA synthesis Effects 0.000 description 2
- 108020004511 Recombinant DNA Proteins 0.000 description 2
- 108091028664 Ribonucleotide Proteins 0.000 description 2
- 102000004142 Trypsin Human genes 0.000 description 2
- 108090000631 Trypsin Proteins 0.000 description 2
- DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 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
- 230000009471 action Effects 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 239000012190 activator Substances 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 230000000996 additive effect Effects 0.000 description 2
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound 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 2
- 230000009833 antibody interaction Effects 0.000 description 2
- 238000001574 biopsy Methods 0.000 description 2
- 125000001246 bromo group Chemical group Br* 0.000 description 2
- 239000001506 calcium phosphate Substances 0.000 description 2
- 229910000389 calcium phosphate Inorganic materials 0.000 description 2
- 235000011010 calcium phosphates Nutrition 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 238000013270 controlled release Methods 0.000 description 2
- 238000004132 cross linking Methods 0.000 description 2
- 229940104302 cytosine Drugs 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 239000005547 deoxyribonucleotide Substances 0.000 description 2
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 238000001962 electrophoresis Methods 0.000 description 2
- 238000005538 encapsulation Methods 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 2
- 238000001502 gel electrophoresis Methods 0.000 description 2
- 102000057382 human EPHA3 Human genes 0.000 description 2
- FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical compound O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 description 2
- 239000007943 implant Substances 0.000 description 2
- 238000011065 in-situ storage Methods 0.000 description 2
- 239000000138 intercalating agent Substances 0.000 description 2
- 238000001638 lipofection Methods 0.000 description 2
- 239000002502 liposome Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 230000008774 maternal effect Effects 0.000 description 2
- 239000003094 microcapsule Substances 0.000 description 2
- 238000010369 molecular cloning Methods 0.000 description 2
- 210000002569 neuron Anatomy 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 230000009871 nonspecific binding Effects 0.000 description 2
- 239000002777 nucleoside Substances 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 230000002062 proliferating effect Effects 0.000 description 2
- 238000002731 protein assay Methods 0.000 description 2
- 238000011002 quantification Methods 0.000 description 2
- 238000003753 real-time PCR Methods 0.000 description 2
- 230000010837 receptor-mediated endocytosis Effects 0.000 description 2
- 230000010076 replication Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 239000002342 ribonucleoside Substances 0.000 description 2
- 239000002336 ribonucleotide Substances 0.000 description 2
- 125000002652 ribonucleotide group Chemical group 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 2
- 239000012096 transfection reagent Substances 0.000 description 2
- 230000001052 transient effect Effects 0.000 description 2
- 238000003146 transient transfection Methods 0.000 description 2
- 238000013519 translation Methods 0.000 description 2
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 2
- 239000012588 trypsin Substances 0.000 description 2
- 229940035893 uracil Drugs 0.000 description 2
- 230000003612 virological effect Effects 0.000 description 2
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 1
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 1
- 229930024421 Adenine Natural products 0.000 description 1
- 108091023037 Aptamer Proteins 0.000 description 1
- 101100114361 Arabidopsis thaliana COL7 gene Proteins 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 235000003351 Brassica cretica Nutrition 0.000 description 1
- 235000003343 Brassica rupestris Nutrition 0.000 description 1
- 241000219193 Brassicaceae Species 0.000 description 1
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 1
- 101150029409 CFTR gene Proteins 0.000 description 1
- 101100114362 Caenorhabditis elegans col-7 gene Proteins 0.000 description 1
- 108010001857 Cell Surface Receptors Proteins 0.000 description 1
- 102000000844 Cell Surface Receptors Human genes 0.000 description 1
- 102100024335 Collagen alpha-1(VII) chain Human genes 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 239000004971 Cross linker Substances 0.000 description 1
- 241000724252 Cucumber mosaic virus Species 0.000 description 1
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 1
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 1
- 206010048768 Dermatosis Diseases 0.000 description 1
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 208000010975 Dystrophic epidermolysis bullosa Diseases 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 108090000982 GIR1 ribozyme Proteins 0.000 description 1
- 108700039691 Genetic Promoter Regions Proteins 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 102100021519 Hemoglobin subunit beta Human genes 0.000 description 1
- 108091005904 Hemoglobin subunit beta Proteins 0.000 description 1
- 241000724709 Hepatitis delta virus Species 0.000 description 1
- 101100384746 Homo sapiens COL17A1 gene Proteins 0.000 description 1
- 101000909498 Homo sapiens Collagen alpha-1(VII) chain Proteins 0.000 description 1
- 241000701806 Human papillomavirus Species 0.000 description 1
- 101000767631 Human papillomavirus type 16 Protein E7 Proteins 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
- 101710203526 Integrase Proteins 0.000 description 1
- 102100040445 Keratin, type I cytoskeletal 14 Human genes 0.000 description 1
- 108010066321 Keratin-14 Proteins 0.000 description 1
- 125000002066 L-histidyl group Chemical group [H]N1C([H])=NC(C([H])([H])[C@](C(=O)[*])([H])N([H])[H])=C1[H] 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- GDBQQVLCIARPGH-UHFFFAOYSA-N Leupeptin Natural products CC(C)CC(NC(C)=O)C(=O)NC(CC(C)C)C(=O)NC(C=O)CCCN=C(N)N GDBQQVLCIARPGH-UHFFFAOYSA-N 0.000 description 1
- 102100031784 Loricrin Human genes 0.000 description 1
- 241000408521 Lucida Species 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 108090000157 Metallothionein Proteins 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 108091061960 Naked DNA Proteins 0.000 description 1
- 208000009869 Neu-Laxova syndrome Diseases 0.000 description 1
- 239000000020 Nitrocellulose Substances 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- 108700026244 Open Reading Frames Proteins 0.000 description 1
- 238000012408 PCR amplification Methods 0.000 description 1
- 238000010222 PCR analysis Methods 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 108700036129 Plectins Proteins 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- KDCGOANMDULRCW-UHFFFAOYSA-N Purine Natural products N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 1
- 238000002123 RNA extraction Methods 0.000 description 1
- 102000044126 RNA-Binding Proteins Human genes 0.000 description 1
- 108700020471 RNA-Binding Proteins Proteins 0.000 description 1
- 230000004570 RNA-binding Effects 0.000 description 1
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 1
- 238000011529 RT qPCR Methods 0.000 description 1
- 108091027981 Response element Proteins 0.000 description 1
- 102000006382 Ribonucleases Human genes 0.000 description 1
- 108010083644 Ribonucleases Proteins 0.000 description 1
- 241000714474 Rous sarcoma virus Species 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 239000002262 Schiff base Substances 0.000 description 1
- 150000004753 Schiff bases Chemical class 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 241000251131 Sphyrna Species 0.000 description 1
- 108091081024 Start codon Proteins 0.000 description 1
- 241000223892 Tetrahymena Species 0.000 description 1
- 102000006601 Thymidine Kinase Human genes 0.000 description 1
- 108020004440 Thymidine kinase Proteins 0.000 description 1
- 102000006986 U2 Small Nuclear Ribonucleoprotein Human genes 0.000 description 1
- 108010072724 U2 Small Nuclear Ribonucleoprotein Proteins 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 229960000643 adenine Drugs 0.000 description 1
- 229960005305 adenosine Drugs 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 239000011543 agarose gel Substances 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 238000005349 anion exchange Methods 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 230000002238 attenuated effect Effects 0.000 description 1
- 150000001540 azides Chemical class 0.000 description 1
- 210000000270 basal cell Anatomy 0.000 description 1
- 210000002469 basement membrane Anatomy 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- DRTQHJPVMGBUCF-PSQAKQOGSA-N beta-L-uridine Natural products O[C@H]1[C@@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-PSQAKQOGSA-N 0.000 description 1
- 238000001815 biotherapy Methods 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000008499 blood brain barrier function Effects 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 210000001218 blood-brain barrier Anatomy 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 150000004657 carbamic acid derivatives Chemical class 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 108091092356 cellular DNA Proteins 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000004700 cellular uptake Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000013043 chemical agent Substances 0.000 description 1
- 238000002144 chemical decomposition reaction Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 238000012411 cloning technique Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 238000007398 colorimetric assay Methods 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 230000000875 corresponding effect Effects 0.000 description 1
- 239000003431 cross linking reagent Substances 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 108010007093 dispase Proteins 0.000 description 1
- 230000007066 double-strand break repair via synthesis-dependent strand annealing Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 230000005014 ectopic expression Effects 0.000 description 1
- 208000004298 epidermolysis bullosa dystrophica Diseases 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 210000005081 epithelial layer Anatomy 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 210000003013 erythroid precursor cell Anatomy 0.000 description 1
- 238000012869 ethanol precipitation Methods 0.000 description 1
- 239000013613 expression plasmid Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 210000003953 foreskin Anatomy 0.000 description 1
- 239000012737 fresh medium Substances 0.000 description 1
- 101150036617 fu gene Proteins 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 230000005021 gait Effects 0.000 description 1
- 238000002523 gelfiltration Methods 0.000 description 1
- 208000030085 generalized junctional epidermolysis bullosa non-Herlitz type Diseases 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 210000000442 hair follicle cell Anatomy 0.000 description 1
- 208000002672 hepatitis B Diseases 0.000 description 1
- 239000012145 high-salt buffer Substances 0.000 description 1
- 230000006801 homologous recombination Effects 0.000 description 1
- 238000002744 homologous recombination Methods 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 239000000017 hydrogel Substances 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 238000010185 immunofluorescence analysis Methods 0.000 description 1
- 238000001114 immunoprecipitation Methods 0.000 description 1
- 238000007901 in situ hybridization Methods 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 102000007236 involucrin Human genes 0.000 description 1
- 108010033564 involucrin Proteins 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 201000001338 junctional epidermolysis bullosa non-Herlitz type Diseases 0.000 description 1
- 108010028309 kalinin Proteins 0.000 description 1
- 210000003292 kidney cell Anatomy 0.000 description 1
- GDBQQVLCIARPGH-ULQDDVLXSA-N leupeptin Chemical compound CC(C)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C=O)CCCN=C(N)N GDBQQVLCIARPGH-ULQDDVLXSA-N 0.000 description 1
- 108010052968 leupeptin Proteins 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 238000002690 local anesthesia Methods 0.000 description 1
- 108010079309 loricrin Proteins 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- YACKEPLHDIMKIO-UHFFFAOYSA-N methylphosphonic acid Chemical class CP(O)(O)=O YACKEPLHDIMKIO-UHFFFAOYSA-N 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 201000006938 muscular dystrophy Diseases 0.000 description 1
- 235000010460 mustard Nutrition 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 210000002445 nipple Anatomy 0.000 description 1
- 229920001220 nitrocellulos Polymers 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 150000003833 nucleoside derivatives Chemical class 0.000 description 1
- 125000003835 nucleoside group Chemical group 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 229920002113 octoxynol Polymers 0.000 description 1
- 238000002515 oligonucleotide synthesis Methods 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 230000008775 paternal effect Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 229940083251 peripheral vasodilators purine derivative Drugs 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 150000005041 phenanthrolines Chemical class 0.000 description 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
- 150000008298 phosphoramidates Chemical class 0.000 description 1
- LFGREXWGYUGZLY-UHFFFAOYSA-N phosphoryl Chemical group [P]=O LFGREXWGYUGZLY-UHFFFAOYSA-N 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 238000013326 plasmid cotransfection Methods 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 1
- 230000008488 polyadenylation Effects 0.000 description 1
- 229920000768 polyamine Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 150000003212 purines Chemical class 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- 229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 description 1
- 238000012207 quantitative assay Methods 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 1
- PYWVYCXTNDRMGF-UHFFFAOYSA-N rhodamine B Chemical compound [Cl-].C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=CC=C1C(O)=O PYWVYCXTNDRMGF-UHFFFAOYSA-N 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 229920000260 silastic Polymers 0.000 description 1
- 238000007390 skin biopsy Methods 0.000 description 1
- 230000008470 skin growth Effects 0.000 description 1
- 210000004511 skin melanocyte Anatomy 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 238000010257 thawing Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 1
- 229940113082 thymine Drugs 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108700012359 toxins Proteins 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000006276 transfer reaction Methods 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 210000001364 upper extremity Anatomy 0.000 description 1
- DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 description 1
- 229940045145 uridine Drugs 0.000 description 1
- 210000005167 vascular cell Anatomy 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Images
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
- 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
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
- C07H21/02—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with ribosyl as saccharide radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
- C07H21/04—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with deoxyribosyl as saccharide radical
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2510/00—Genetically modified cells
Landscapes
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- Biomedical Technology (AREA)
- General Health & Medical Sciences (AREA)
- General Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Physics & Mathematics (AREA)
- Biophysics (AREA)
- Plant Pathology (AREA)
- Microbiology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US10/198,447 US20040018622A1 (en) | 2002-07-17 | 2002-07-17 | Spliceosome mediated RNA trans-splicing for correction of skin disorders |
| PCT/US2003/022469 WO2004006678A1 (en) | 2002-07-17 | 2003-07-17 | Spliceosome mediated rna trans-splicing for correction of skin disorders |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2005532815A true JP2005532815A (ja) | 2005-11-04 |
| JP2005532815A5 JP2005532815A5 (enExample) | 2006-06-08 |
Family
ID=30115154
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2004521968A Withdrawn JP2005532815A (ja) | 2002-07-17 | 2003-07-17 | 皮膚疾患の修正のためのスプライセオソームにより媒介されるｒｎａトランススプライシング |
Country Status (6)
| Country | Link |
|---|---|
| US (2) | US20040018622A1 (enExample) |
| EP (1) | EP1542532A1 (enExample) |
| JP (1) | JP2005532815A (enExample) |
| AU (1) | AU2003256606A1 (enExample) |
| CA (1) | CA2492469A1 (enExample) |
| WO (1) | WO2004006678A1 (enExample) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2010521150A (ja) * | 2007-10-25 | 2010-06-24 | ナショナル キャンサー センター | トランス−スプライシングリボザイムを保有するアデノウイルスを用いた、分子イメージングによる疾病の診断方法 |
| JP2011529333A (ja) * | 2008-07-30 | 2011-12-08 | ヨハン バウアー | 改善されたプレ−ｍＲＮＡトランススプライシング分子（ＲＴＭ）分子およびその使用 |
| JP2014132021A (ja) * | 2008-04-14 | 2014-07-17 | General Hospital Corp | 膵管腺癌の検出および治療のためのプレクチン−１標的化剤 |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007518423A (ja) * | 2004-01-23 | 2007-07-12 | イントロン、インコーポレイテッド | スプライセオソーム仲介型ｒｎａトランススプライシングを使用するアポａ−１及びその変異体の発現 |
| AU2005210679B2 (en) * | 2004-02-03 | 2009-10-01 | Hybrid Biosciences Pty Ltd | Method of identifying genes which promote hybrid vigour and hybrid debility and uses thereof |
| US20110252488A1 (en) * | 2004-02-03 | 2011-10-13 | Peter Hamilton Kay | Method of Identifying Genes which Promote Hybrid Vigour and Hybrid Debility and Uses Thereof |
| US20060134658A1 (en) * | 2004-08-09 | 2006-06-22 | Garcia-Blanco Mariano A | Use of RNA trans-splicing for generation of interfering RNA molecules |
| KR20080040735A (ko) * | 2005-07-29 | 2008-05-08 | 하이브리드 바이오사이언시스 피티와이 엘티디 | 잡종 강세 또는 잡종 약세를 촉진시키는 유전자 및 그산물의 동정 방법 및 이의 용도 |
| GB201219762D0 (en) | 2012-11-02 | 2012-12-19 | Bauer Johann | A RNA trans-splicing molecule (RTM) for use in the treatment of cancer |
| US10987433B2 (en) | 2015-11-19 | 2021-04-27 | The Trustees Of The University Of Pennsylvania | Compositions and methods for correction of heritable ocular disease |
| CA3097004A1 (en) | 2018-04-17 | 2019-10-24 | The Trustees Of The University Of Pennsylvania | Trans-splicing molecules |
| GB2634434A (en) | 2022-05-13 | 2025-04-09 | Ascidian Therapeutics Inc | ABCA4 trans-splicing molecules |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5914265A (en) * | 1992-04-30 | 1999-06-22 | Baylor College Of Medicine | Keratin K1 expression vectors and methods of use |
| US5874560A (en) * | 1994-04-22 | 1999-02-23 | The United States Of America As Represented By The Department Of Health And Human Services | Melanoma antigens and their use in diagnostic and therapeutic methods |
| US5872241A (en) * | 1995-01-25 | 1999-02-16 | The Trustees Of Columbia University In The City Of New York | Multiple component RNA catalysts and uses thereof |
| US6280978B1 (en) * | 1995-12-15 | 2001-08-28 | Intronn Holdings, Llc | Methods and compositions for use in spliceosome mediated RNA trans-splicing |
| DE69636937T3 (de) * | 1995-12-15 | 2011-01-05 | Virxsys Corp. | Durch trans-spaltung erhaltene therapeutische molekule |
| US6083702A (en) * | 1995-12-15 | 2000-07-04 | Intronn Holdings Llc | Methods and compositions for use in spliceosome mediated RNA trans-splicing |
-
2002
- 2002-07-17 US US10/198,447 patent/US20040018622A1/en not_active Abandoned
-
2003
- 2003-07-17 AU AU2003256606A patent/AU2003256606A1/en not_active Abandoned
- 2003-07-17 EP EP03764802A patent/EP1542532A1/en not_active Withdrawn
- 2003-07-17 WO PCT/US2003/022469 patent/WO2004006678A1/en not_active Ceased
- 2003-07-17 CA CA002492469A patent/CA2492469A1/en not_active Abandoned
- 2003-07-17 JP JP2004521968A patent/JP2005532815A/ja not_active Withdrawn
- 2003-07-17 US US10/621,867 patent/US20040248141A1/en not_active Abandoned
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2010521150A (ja) * | 2007-10-25 | 2010-06-24 | ナショナル キャンサー センター | トランス−スプライシングリボザイムを保有するアデノウイルスを用いた、分子イメージングによる疾病の診断方法 |
| JP2014132021A (ja) * | 2008-04-14 | 2014-07-17 | General Hospital Corp | 膵管腺癌の検出および治療のためのプレクチン−１標的化剤 |
| US9387265B2 (en) | 2008-04-14 | 2016-07-12 | The General Hospital Corporation | Plectin-1 targeted agents for detection and treatment of pancreatic ductal adenocarcinoma |
| US10124077B2 (en) | 2008-04-14 | 2018-11-13 | The General Hospital Corporation | Plectin-1 targeted agents for detection and treatment of pancreatic ductal adenocarcinoma |
| JP2011529333A (ja) * | 2008-07-30 | 2011-12-08 | ヨハン バウアー | 改善されたプレ−ｍＲＮＡトランススプライシング分子（ＲＴＭ）分子およびその使用 |
Also Published As
| Publication number | Publication date |
|---|---|
| EP1542532A1 (en) | 2005-06-22 |
| US20040248141A1 (en) | 2004-12-09 |
| WO2004006678A1 (en) | 2004-01-22 |
| CA2492469A1 (en) | 2004-01-22 |
| AU2003256606A1 (en) | 2004-02-02 |
| US20040018622A1 (en) | 2004-01-29 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US6280978B1 (en) | Methods and compositions for use in spliceosome mediated RNA trans-splicing | |
| JP5735912B2 (ja) | 改善されたプレ−ｍＲＮＡトランススプライシング分子（ＲＴＭ）分子およびその使用 | |
| JP2022081503A (ja) | ＣＲＩＳＰＲ／Ｃａｓ９の核送達を通じた細胞ＲＮＡの追跡と操作 | |
| Wally et al. | Spliceosome-mediated trans-splicing: the therapeutic cut and paste | |
| CA3106738C (en) | METHOD FOR MODULATING RNA SPLICING BY INDUCING A BASE MUTATION AT A SPLICE SITE OR A BASE SUBSTITUTION IN A POLYPYRIMIDIN REGION | |
| Dallinger et al. | Development of spliceosome‐mediated RNA trans‐splicing (SMaRT™) for the correction of inherited skin diseases | |
| US20060234247A1 (en) | Correction of alpha-1-antitrypsin genetic defects using spliceosome mediated RNA trans splicing | |
| JP2005532815A (ja) | 皮膚疾患の修正のためのスプライセオソームにより媒介されるｒｎａトランススプライシング | |
| Vanslambrouck et al. | Direct reprogramming to human nephron progenitor-like cells using inducible piggyBac transposon expression of SNAI2-EYA1-SIX1 | |
| Chow et al. | Characterization of expression at the human XIST locus in somatic, embryonal carcinoma, and transgenic cell lines | |
| Ha et al. | Tissue‐specific protein‐DNA interactions of the mouse protamine 2 gene promoter | |
| US20060246422A1 (en) | Methods and compositions for use in spliceosome mediated RNA trans-splicing | |
| WO2022266538A2 (en) | Compositions and methods for targeting, editing or modifying human genes | |
| JP2005168509A (ja) | スプライセオソームにより媒介されるｒｎａトランススプライシング | |
| EP4274897A2 (en) | Genome editing approaches to treat spinal muscular atrophy | |
| EP1384784A1 (en) | Method for reversible inhibition of gene expression by modified ribonucleoproteins | |
| JP5676140B2 (ja) | ヒト癌化細胞の作製方法 | |
| WO2003069311A2 (en) | Methods and compositions for use in spliceosome mediated rna trans-splicing | |
| AU2004237884B2 (en) | Spliceosome mediated RNA trans-splicing | |
| JP2009000120A (ja) | スプライソソーム媒介ｒｎａトランス−スプライシングにおける使用のための方法及び組成物 | |
| US20040038396A1 (en) | Spliceosome mediated RNA trans-splicing for correction of factor VIII genetic defects | |
| HK40036693A (en) | Method for modulating rna splicing by inducing base mutation at splice site or base substitution in polypyrimidine region | |
| Garnier | Study of transcription regulation of the gene mdr1 | |
| JPWO2014122729A1 (ja) | ヒト由来細胞の特異細胞の作製方法 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20060412 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20060412 |
|
| A761 | Written withdrawal of application |
Free format text: JAPANESE INTERMEDIATE CODE: A761 Effective date: 20070205 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20070207 |