AU735788B2 - Materials and methods for ribozyme treatment of diseases - Google Patents
Materials and methods for ribozyme treatment of diseases Download PDFInfo
- Publication number
- AU735788B2 AU735788B2 AU71406/98A AU7140698A AU735788B2 AU 735788 B2 AU735788 B2 AU 735788B2 AU 71406/98 A AU71406/98 A AU 71406/98A AU 7140698 A AU7140698 A AU 7140698A AU 735788 B2 AU735788 B2 AU 735788B2
- Authority
- AU
- Australia
- Prior art keywords
- ribozyme
- composition according
- retinal
- ribozymes
- mutant
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Ceased
Links
- 108090000994 Catalytic RNA Proteins 0.000 title claims description 148
- 102000053642 Catalytic RNA Human genes 0.000 title claims description 146
- 108091092562 ribozyme Proteins 0.000 title claims description 146
- 238000000034 method Methods 0.000 title claims description 33
- 201000010099 disease Diseases 0.000 title claims description 19
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims description 19
- 239000000463 material Substances 0.000 title description 11
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 claims description 147
- 102200141512 rs104893768 Human genes 0.000 claims description 58
- 108090000623 proteins and genes Proteins 0.000 claims description 47
- 108020004999 messenger RNA Proteins 0.000 claims description 39
- 230000002207 retinal effect Effects 0.000 claims description 29
- 210000004027 cell Anatomy 0.000 claims description 27
- 230000014509 gene expression Effects 0.000 claims description 25
- 238000002347 injection Methods 0.000 claims description 25
- 239000007924 injection Substances 0.000 claims description 25
- 239000000203 mixture Substances 0.000 claims description 23
- 241000702421 Dependoparvovirus Species 0.000 claims description 19
- 108010005063 Rod Opsins Proteins 0.000 claims description 19
- 230000000694 effects Effects 0.000 claims description 18
- 102000005801 Rod Opsins Human genes 0.000 claims description 17
- 241000700605 Viruses Species 0.000 claims description 17
- 206010012689 Diabetic retinopathy Diseases 0.000 claims description 14
- 239000013598 vector Substances 0.000 claims description 13
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 claims description 11
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 claims description 11
- 210000004155 blood-retinal barrier Anatomy 0.000 claims description 11
- 230000004378 blood-retinal barrier Effects 0.000 claims description 11
- 102000004169 proteins and genes Human genes 0.000 claims description 10
- 210000000608 photoreceptor cell Anatomy 0.000 claims description 9
- 241000894007 species Species 0.000 claims description 8
- 241001529936 Murinae Species 0.000 claims description 7
- 208000017442 Retinal disease Diseases 0.000 claims description 7
- 230000004064 dysfunction Effects 0.000 claims description 7
- 241000283690 Bos taurus Species 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 230000002829 reductive effect Effects 0.000 claims description 5
- 102100028452 Nitric oxide synthase, endothelial Human genes 0.000 claims description 4
- 101710090055 Nitric oxide synthase, endothelial Proteins 0.000 claims description 4
- 206010038910 Retinitis Diseases 0.000 claims description 4
- 230000001575 pathological effect Effects 0.000 claims description 4
- 230000001105 regulatory effect Effects 0.000 claims description 3
- 101150073388 rpl3 gene Proteins 0.000 claims description 3
- 108091028043 Nucleic acid sequence Proteins 0.000 claims 4
- 150000007523 nucleic acids Chemical group 0.000 claims 4
- 102100029438 Nitric oxide synthase, inducible Human genes 0.000 claims 3
- 101710089543 Nitric oxide synthase, inducible Proteins 0.000 claims 3
- 241000124008 Mammalia Species 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 210000001525 retina Anatomy 0.000 description 46
- 229920002477 rna polymer Polymers 0.000 description 43
- 108091008695 photoreceptors Proteins 0.000 description 39
- 108091034117 Oligonucleotide Proteins 0.000 description 35
- 241000700159 Rattus Species 0.000 description 30
- 108020004414 DNA Proteins 0.000 description 27
- 238000003776 cleavage reaction Methods 0.000 description 25
- 239000000047 product Substances 0.000 description 24
- 208000007014 Retinitis pigmentosa Diseases 0.000 description 23
- 230000007017 scission Effects 0.000 description 22
- 102220017356 rs118203481 Human genes 0.000 description 21
- 108090001102 Hammerhead ribozyme Proteins 0.000 description 20
- 230000035772 mutation Effects 0.000 description 19
- 102000010175 Opsin Human genes 0.000 description 18
- 108050001704 Opsin Proteins 0.000 description 18
- 108700019146 Transgenes Proteins 0.000 description 18
- 241000251131 Sphyrna Species 0.000 description 17
- 238000003556 assay Methods 0.000 description 14
- 239000002773 nucleotide Substances 0.000 description 14
- 125000003729 nucleotide group Chemical group 0.000 description 14
- 210000003583 retinal pigment epithelium Anatomy 0.000 description 14
- 230000009261 transgenic effect Effects 0.000 description 14
- 102000011779 Nitric Oxide Synthase Type II Human genes 0.000 description 13
- 108010076864 Nitric Oxide Synthase Type II Proteins 0.000 description 13
- 108090001052 hairpin ribozyme Proteins 0.000 description 13
- 239000013612 plasmid Substances 0.000 description 13
- 238000003757 reverse transcription PCR Methods 0.000 description 13
- 201000007737 Retinal degeneration Diseases 0.000 description 12
- 238000006243 chemical reaction Methods 0.000 description 12
- 230000004258 retinal degeneration Effects 0.000 description 12
- 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 11
- 230000001965 increasing effect Effects 0.000 description 11
- 239000000758 substrate Substances 0.000 description 11
- 238000011144 upstream manufacturing Methods 0.000 description 11
- 241001465754 Metazoa Species 0.000 description 10
- 239000012634 fragment Substances 0.000 description 10
- 208000002780 macular degeneration Diseases 0.000 description 10
- 238000011534 incubation Methods 0.000 description 9
- 230000002458 infectious effect Effects 0.000 description 9
- 239000002245 particle Substances 0.000 description 9
- 230000008685 targeting Effects 0.000 description 9
- OPIFSICVWOWJMJ-AEOCFKNESA-N 5-bromo-4-chloro-3-indolyl beta-D-galactoside Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1OC1=CNC2=CC=C(Br)C(Cl)=C12 OPIFSICVWOWJMJ-AEOCFKNESA-N 0.000 description 8
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 8
- 230000003197 catalytic effect Effects 0.000 description 8
- 206010012601 diabetes mellitus Diseases 0.000 description 8
- 210000002889 endothelial cell Anatomy 0.000 description 8
- 101150066555 lacZ gene Proteins 0.000 description 8
- 239000011777 magnesium Substances 0.000 description 8
- 235000018102 proteins Nutrition 0.000 description 8
- 210000005078 rod cell inner segment Anatomy 0.000 description 8
- 210000004358 rod cell outer segment Anatomy 0.000 description 8
- 210000001519 tissue Anatomy 0.000 description 8
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 7
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 7
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 7
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 7
- 108700008625 Reporter Genes Proteins 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 7
- 239000008103 glucose Substances 0.000 description 7
- 229910052749 magnesium Inorganic materials 0.000 description 7
- 241000701161 unidentified adenovirus Species 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 102000008299 Nitric Oxide Synthase Human genes 0.000 description 6
- 108010021487 Nitric Oxide Synthase Proteins 0.000 description 6
- 108090000820 Rhodopsin Proteins 0.000 description 6
- 230000008901 benefit Effects 0.000 description 6
- 230000007423 decrease Effects 0.000 description 6
- 108020004705 Codon Proteins 0.000 description 5
- 241000282412 Homo Species 0.000 description 5
- 241000699670 Mus sp. Species 0.000 description 5
- 238000010276 construction Methods 0.000 description 5
- 230000006378 damage Effects 0.000 description 5
- 238000011161 development Methods 0.000 description 5
- 210000003038 endothelium Anatomy 0.000 description 5
- 230000004438 eyesight Effects 0.000 description 5
- 238000001727 in vivo Methods 0.000 description 5
- 238000005259 measurement Methods 0.000 description 5
- 230000007246 mechanism Effects 0.000 description 5
- NCYCYZXNIZJOKI-IOUUIBBYSA-N 11-cis-retinal Chemical compound O=C/C=C(\C)/C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C NCYCYZXNIZJOKI-IOUUIBBYSA-N 0.000 description 4
- 229920000936 Agarose Polymers 0.000 description 4
- 201000004569 Blindness Diseases 0.000 description 4
- 108020004635 Complementary DNA Proteins 0.000 description 4
- 102000004330 Rhodopsin Human genes 0.000 description 4
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 4
- 230000000692 anti-sense effect Effects 0.000 description 4
- 239000002299 complementary DNA Substances 0.000 description 4
- 239000003102 growth factor Substances 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 208000015181 infectious disease Diseases 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 238000012453 sprague-dawley rat model Methods 0.000 description 4
- 238000010186 staining Methods 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 108091026890 Coding region Proteins 0.000 description 3
- 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 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- 208000028782 Hereditary disease Diseases 0.000 description 3
- YQEZLKZALYSWHR-UHFFFAOYSA-N Ketamine Chemical compound C=1C=CC=C(Cl)C=1C1(NC)CCCCC1=O YQEZLKZALYSWHR-UHFFFAOYSA-N 0.000 description 3
- RHGKLRLOHDJJDR-BYPYZUCNSA-N L-citrulline Chemical compound NC(=O)NCCC[C@H]([NH3+])C([O-])=O RHGKLRLOHDJJDR-BYPYZUCNSA-N 0.000 description 3
- 206010025421 Macule Diseases 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- 108010029485 Protein Isoforms Proteins 0.000 description 3
- 102000001708 Protein Isoforms Human genes 0.000 description 3
- 238000010240 RT-PCR analysis Methods 0.000 description 3
- 101710137500 T7 RNA polymerase Proteins 0.000 description 3
- 230000002159 abnormal effect Effects 0.000 description 3
- 230000003321 amplification Effects 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 108020001778 catalytic domains Proteins 0.000 description 3
- 210000005056 cell body Anatomy 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 230000000875 corresponding effect Effects 0.000 description 3
- 238000010586 diagram Methods 0.000 description 3
- 230000008030 elimination Effects 0.000 description 3
- 238000003379 elimination reaction Methods 0.000 description 3
- 108010030074 endodeoxyribonuclease MluI Proteins 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- 230000002068 genetic effect Effects 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- 229960003299 ketamine Drugs 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 238000003199 nucleic acid amplification method Methods 0.000 description 3
- 230000002093 peripheral effect Effects 0.000 description 3
- 230000008488 polyadenylation Effects 0.000 description 3
- 230000000717 retained effect Effects 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 238000010361 transduction Methods 0.000 description 3
- 230000026683 transduction Effects 0.000 description 3
- 239000013603 viral vector Substances 0.000 description 3
- 230000003612 virological effect Effects 0.000 description 3
- 239000013607 AAV vector Substances 0.000 description 2
- 108700028369 Alleles Proteins 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 2
- 102000004218 Insulin-Like Growth Factor I Human genes 0.000 description 2
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- 238000002123 RNA extraction Methods 0.000 description 2
- 206010063837 Reperfusion injury Diseases 0.000 description 2
- PGAVKCOVUIYSFO-XVFCMESISA-N UTP Chemical compound O[C@@H]1[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O[C@H]1N1C(=O)NC(=O)C=C1 PGAVKCOVUIYSFO-XVFCMESISA-N 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 239000004202 carbamide Substances 0.000 description 2
- 210000004323 caveolae Anatomy 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 229960002173 citrulline Drugs 0.000 description 2
- 210000004087 cornea Anatomy 0.000 description 2
- 230000000120 cytopathologic effect Effects 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 230000007850 degeneration Effects 0.000 description 2
- 230000029087 digestion Effects 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 238000001962 electrophoresis Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 210000001723 extracellular space Anatomy 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 238000001476 gene delivery Methods 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 230000001771 impaired effect Effects 0.000 description 2
- 238000011081 inoculation Methods 0.000 description 2
- 208000012947 ischemia reperfusion injury Diseases 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 238000000329 molecular dynamics simulation Methods 0.000 description 2
- 230000001537 neural effect Effects 0.000 description 2
- 210000005157 neural retina Anatomy 0.000 description 2
- 210000003733 optic disk Anatomy 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 230000005043 peripheral vision Effects 0.000 description 2
- 230000035699 permeability Effects 0.000 description 2
- 230000002085 persistent effect Effects 0.000 description 2
- 230000019612 pigmentation Effects 0.000 description 2
- 108091033319 polynucleotide Proteins 0.000 description 2
- 102000040430 polynucleotide Human genes 0.000 description 2
- 239000002157 polynucleotide Substances 0.000 description 2
- 238000004321 preservation Methods 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 230000000750 progressive effect Effects 0.000 description 2
- 239000013608 rAAV vector Substances 0.000 description 2
- 238000010839 reverse transcription Methods 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 238000012163 sequencing technique Methods 0.000 description 2
- 238000013207 serial dilution Methods 0.000 description 2
- 239000013589 supplement Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 230000000946 synaptic effect Effects 0.000 description 2
- 238000013518 transcription Methods 0.000 description 2
- 230000035897 transcription Effects 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- 241001529453 unidentified herpesvirus Species 0.000 description 2
- 229950010342 uridine triphosphate Drugs 0.000 description 2
- PGAVKCOVUIYSFO-UHFFFAOYSA-N uridine-triphosphate Natural products OC1C(O)C(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)OC1N1C(=O)NC(=O)C=C1 PGAVKCOVUIYSFO-UHFFFAOYSA-N 0.000 description 2
- 230000004393 visual impairment Effects 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- BPICBUSOMSTKRF-UHFFFAOYSA-N xylazine Chemical compound CC1=CC=CC(C)=C1NC1=NCCCS1 BPICBUSOMSTKRF-UHFFFAOYSA-N 0.000 description 2
- 229960001600 xylazine Drugs 0.000 description 2
- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 description 1
- 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 1
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 1
- 108020005544 Antisense RNA Proteins 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 101100469268 Caenorhabditis elegans rpl-1 gene Proteins 0.000 description 1
- 208000010693 Charcot-Marie-Tooth Disease Diseases 0.000 description 1
- 208000033810 Choroidal dystrophy Diseases 0.000 description 1
- 108010017826 DNA Polymerase I Proteins 0.000 description 1
- 102000004594 DNA Polymerase I Human genes 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
- 206010061818 Disease progression Diseases 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 102000002464 Galactosidases Human genes 0.000 description 1
- 108010093031 Galactosidases Proteins 0.000 description 1
- 208000003098 Ganglion Cysts Diseases 0.000 description 1
- 108010043121 Green Fluorescent Proteins Proteins 0.000 description 1
- 208000007698 Gyrate Atrophy Diseases 0.000 description 1
- 241000724709 Hepatitis delta virus Species 0.000 description 1
- 208000026350 Inborn Genetic disease Diseases 0.000 description 1
- 108091092195 Intron Proteins 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 1
- 229930064664 L-arginine Natural products 0.000 description 1
- 235000014852 L-arginine Nutrition 0.000 description 1
- 208000035719 Maculopathy Diseases 0.000 description 1
- 101000586066 Mus musculus Rhodopsin Proteins 0.000 description 1
- 108091061960 Naked DNA Proteins 0.000 description 1
- RHGKLRLOHDJJDR-UHFFFAOYSA-N Ndelta-carbamoyl-DL-ornithine Natural products OC(=O)C(N)CCCNC(N)=O RHGKLRLOHDJJDR-UHFFFAOYSA-N 0.000 description 1
- 229930193140 Neomycin Natural products 0.000 description 1
- 208000001140 Night Blindness Diseases 0.000 description 1
- 208000025464 Norrie disease Diseases 0.000 description 1
- 208000022873 Ocular disease Diseases 0.000 description 1
- 108700020796 Oncogene Proteins 0.000 description 1
- 102000043276 Oncogene Human genes 0.000 description 1
- 238000012408 PCR amplification Methods 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 241001505332 Polyomavirus sp. Species 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 230000007022 RNA scission Effects 0.000 description 1
- 238000011530 RNeasy Mini Kit Methods 0.000 description 1
- 208000005587 Refsum Disease Diseases 0.000 description 1
- 206010038848 Retinal detachment Diseases 0.000 description 1
- 108020005543 Satellite RNA Proteins 0.000 description 1
- 229920005654 Sephadex Polymers 0.000 description 1
- 239000012507 Sephadex™ Substances 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- OUUQCZGPVNCOIJ-UHFFFAOYSA-M Superoxide Chemical compound [O-][O] OUUQCZGPVNCOIJ-UHFFFAOYSA-M 0.000 description 1
- 208000005400 Synovial Cyst Diseases 0.000 description 1
- 108700005078 Synthetic Genes Proteins 0.000 description 1
- 241000278713 Theora Species 0.000 description 1
- 102000006601 Thymidine Kinase Human genes 0.000 description 1
- 108020004440 Thymidine kinase Proteins 0.000 description 1
- BGDKAVGWHJFAGW-UHFFFAOYSA-N Tropicamide Chemical compound C=1C=CC=CC=1C(CO)C(=O)N(CC)CC1=CC=NC=C1 BGDKAVGWHJFAGW-UHFFFAOYSA-N 0.000 description 1
- 108010020713 Tth polymerase Proteins 0.000 description 1
- 206010045178 Tunnel vision Diseases 0.000 description 1
- 108010067390 Viral Proteins Proteins 0.000 description 1
- 206010047571 Visual impairment Diseases 0.000 description 1
- FPIPGXGPPPQFEQ-BOOMUCAASA-N Vitamin A Natural products OC/C=C(/C)\C=C\C=C(\C)/C=C/C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-BOOMUCAASA-N 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 208000037919 acquired disease Diseases 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine group Chemical group [C@@H]1([C@H](O)[C@H](O)[C@@H](CO)O1)N1C=NC=2C(N)=NC=NC12 OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 1
- 208000030597 adult Refsum disease Diseases 0.000 description 1
- 206010064930 age-related macular degeneration Diseases 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 description 1
- 230000001668 ameliorated effect Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 235000009697 arginine Nutrition 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 230000003190 augmentative effect Effects 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000003542 behavioural effect Effects 0.000 description 1
- 102000005936 beta-Galactosidase Human genes 0.000 description 1
- 108010005774 beta-Galactosidase Proteins 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 238000004061 bleaching Methods 0.000 description 1
- 208000002352 blister Diseases 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
- 239000004327 boric acid Substances 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- UDSAIICHUKSCKT-UHFFFAOYSA-N bromophenol blue Chemical compound C1=C(Br)C(O)=C(Br)C=C1C1(C=2C=C(Br)C(O)=C(Br)C=2)C2=CC=CC=C2S(=O)(=O)O1 UDSAIICHUKSCKT-UHFFFAOYSA-N 0.000 description 1
- 238000010805 cDNA synthesis kit Methods 0.000 description 1
- 239000007978 cacodylate buffer Substances 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000006727 cell loss Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 210000003986 cell retinal photoreceptor Anatomy 0.000 description 1
- 108091092328 cellular RNA Proteins 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 210000001627 cerebral artery Anatomy 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- ZYWFEOZQIUMEGL-UHFFFAOYSA-N chloroform;3-methylbutan-1-ol;phenol Chemical compound ClC(Cl)Cl.CC(C)CCO.OC1=CC=CC=C1 ZYWFEOZQIUMEGL-UHFFFAOYSA-N 0.000 description 1
- 210000003161 choroid Anatomy 0.000 description 1
- 208000003571 choroideremia Diseases 0.000 description 1
- 230000002759 chromosomal effect Effects 0.000 description 1
- 235000013477 citrulline Nutrition 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 239000003184 complementary RNA Substances 0.000 description 1
- 201000006754 cone-rod dystrophy Diseases 0.000 description 1
- 238000004624 confocal microscopy Methods 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 238000005520 cutting process Methods 0.000 description 1
- 230000002380 cytological effect Effects 0.000 description 1
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical group NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 1
- SUYVUBYJARFZHO-RRKCRQDMSA-N dATP Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@H]1C[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 SUYVUBYJARFZHO-RRKCRQDMSA-N 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 239000010432 diamond Substances 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 1
- -1 eNOS Proteins 0.000 description 1
- 238000002571 electroretinography Methods 0.000 description 1
- 230000003511 endothelial effect Effects 0.000 description 1
- 210000003989 endothelium vascular Anatomy 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 239000003822 epoxy resin Substances 0.000 description 1
- 238000012869 ethanol precipitation Methods 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 239000013613 expression plasmid Substances 0.000 description 1
- 208000030533 eye disease Diseases 0.000 description 1
- 239000000834 fixative Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 238000002523 gelfiltration Methods 0.000 description 1
- 208000016361 genetic disease Diseases 0.000 description 1
- 230000002518 glial effect Effects 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 125000000487 histidyl group Chemical class [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C([H])=N1 0.000 description 1
- 238000009396 hybridization Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 201000001421 hyperglycemia Diseases 0.000 description 1
- 230000007124 immune defense Effects 0.000 description 1
- 238000003365 immunocytochemistry Methods 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000000415 inactivating effect Effects 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 238000012933 kinetic analysis Methods 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000003589 local anesthetic agent Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- FDZZZRQASAIRJF-UHFFFAOYSA-M malachite green Chemical compound [Cl-].C1=CC(N(C)C)=CC=C1C(C=1C=CC=CC=1)=C1C=CC(=[N+](C)C)C=C1 FDZZZRQASAIRJF-UHFFFAOYSA-M 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 1
- 238000001000 micrograph Methods 0.000 description 1
- 230000004784 molecular pathogenesis Effects 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- 229960004927 neomycin Drugs 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 230000030147 nuclear export Effects 0.000 description 1
- 201000005111 ocular hyperemia Diseases 0.000 description 1
- 238000002577 ophthalmoscopy Methods 0.000 description 1
- 208000014380 ornithine aminotransferase deficiency Diseases 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000007918 pathogenicity Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- DDBREPKUVSBGFI-UHFFFAOYSA-N phenobarbital Chemical compound C=1C=CC=CC=1C1(CC)C(=O)NC(=O)NC1=O DDBREPKUVSBGFI-UHFFFAOYSA-N 0.000 description 1
- 229960002695 phenobarbital Drugs 0.000 description 1
- SONNWYBIRXJNDC-VIFPVBQESA-N phenylephrine Chemical compound CNC[C@H](O)C1=CC=CC(O)=C1 SONNWYBIRXJNDC-VIFPVBQESA-N 0.000 description 1
- 229960001802 phenylephrine Drugs 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- LFGREXWGYUGZLY-UHFFFAOYSA-N phosphoryl Chemical group [P]=O LFGREXWGYUGZLY-UHFFFAOYSA-N 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 210000001127 pigmented epithelial cell Anatomy 0.000 description 1
- 230000004983 pleiotropic effect Effects 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 229920000647 polyepoxide Polymers 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 210000000063 presynaptic terminal Anatomy 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 238000001243 protein synthesis Methods 0.000 description 1
- 230000002488 pyknotic effect Effects 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 239000002516 radical scavenger Substances 0.000 description 1
- 238000011552 rat model Methods 0.000 description 1
- 238000009256 replacement therapy Methods 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 230000000979 retarding effect Effects 0.000 description 1
- 230000004264 retinal detachment Effects 0.000 description 1
- 210000000880 retinal rod photoreceptor cell Anatomy 0.000 description 1
- 238000012340 reverse transcriptase PCR Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000003345 scintillation counting Methods 0.000 description 1
- 210000003786 sclera Anatomy 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000010583 slow cooling Methods 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
- 239000012192 staining solution Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 238000011824 transgenic rat model Methods 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
- 230000005945 translocation Effects 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 235000011178 triphosphate Nutrition 0.000 description 1
- 239000001226 triphosphate Substances 0.000 description 1
- 125000002264 triphosphate group Chemical class [H]OP(=O)(O[H])OP(=O)(O[H])OP(=O)(O[H])O* 0.000 description 1
- 229960004791 tropicamide Drugs 0.000 description 1
- 230000007306 turnover Effects 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 230000029812 viral genome replication Effects 0.000 description 1
- 210000002845 virion Anatomy 0.000 description 1
- 208000029257 vision disease Diseases 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 235000019155 vitamin A Nutrition 0.000 description 1
- 239000011719 vitamin A Substances 0.000 description 1
- 229940045997 vitamin a Drugs 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- NLIVDORGVGAOOJ-MAHBNPEESA-M xylene cyanol Chemical compound [Na+].C1=C(C)C(NCC)=CC=C1C(\C=1C(=CC(OS([O-])=O)=CC=1)OS([O-])=O)=C\1C=C(C)\C(=[NH+]/CC)\C=C/1 NLIVDORGVGAOOJ-MAHBNPEESA-M 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
- 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
- C12N15/1136—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 against growth factors, growth regulators, cytokines, lymphokines or hormones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- 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
- C12N15/1137—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 against enzymes
-
- 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
- C12N15/1138—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 against receptors or cell surface proteins
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2217/00—Genetically modified animals
- A01K2217/05—Animals comprising random inserted nucleic acids (transgenic)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- 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
- C12N2310/11—Antisense
- C12N2310/111—Antisense spanning the whole gene, or a large part of it
-
- 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
- C12N2310/12—Type of nucleic acid catalytic nucleic acids, e.g. ribozymes
- C12N2310/121—Hammerhead
-
- 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
- C12N2310/12—Type of nucleic acid catalytic nucleic acids, e.g. ribozymes
- C12N2310/122—Hairpin
-
- 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
- C12N2310/12—Type of nucleic acid catalytic nucleic acids, e.g. ribozymes
- C12N2310/127—DNAzymes
-
- 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
- C12N2799/00—Uses of viruses
- C12N2799/02—Uses of viruses as vector
- C12N2799/021—Uses of viruses as vector for the expression of a heterologous nucleic acid
- C12N2799/025—Uses of viruses as vector for the expression of a heterologous nucleic acid where the vector is derived from a parvovirus
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Biomedical Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Zoology (AREA)
- General Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Wood Science & Technology (AREA)
- Molecular Biology (AREA)
- General Health & Medical Sciences (AREA)
- Plant Pathology (AREA)
- Microbiology (AREA)
- Biophysics (AREA)
- Physics & Mathematics (AREA)
- Biochemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Endocrinology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Virology (AREA)
- Cardiology (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Ophthalmology & Optometry (AREA)
- Heart & Thoracic Surgery (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Enzymes And Modification Thereof (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US4449297P | 1997-04-21 | 1997-04-21 | |
| US60/044492 | 1997-04-21 | ||
| US4614797P | 1997-05-09 | 1997-05-09 | |
| US60/046147 | 1997-05-09 | ||
| PCT/US1998/007968 WO1998048009A2 (en) | 1997-04-21 | 1998-04-21 | Materials and methods for ribozyme treatment of retinal diseases |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU7140698A AU7140698A (en) | 1998-11-13 |
| AU735788B2 true AU735788B2 (en) | 2001-07-12 |
Family
ID=26721633
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU71406/98A Ceased AU735788B2 (en) | 1997-04-21 | 1998-04-21 | Materials and methods for ribozyme treatment of diseases |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US6225291B1 (https=) |
| EP (1) | EP0977841A2 (https=) |
| JP (1) | JP2001523959A (https=) |
| AU (1) | AU735788B2 (https=) |
| BR (1) | BR9808606A (https=) |
| CA (1) | CA2287508A1 (https=) |
| NZ (1) | NZ500427A (https=) |
| WO (1) | WO1998048009A2 (https=) |
Families Citing this family (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1998048009A2 (en) | 1997-04-21 | 1998-10-29 | University Of Florida | Materials and methods for ribozyme treatment of retinal diseases |
| DE19956568A1 (de) | 1999-01-30 | 2000-08-17 | Roland Kreutzer | Verfahren und Medikament zur Hemmung der Expression eines vorgegebenen Gens |
| EP1183389A2 (en) * | 1999-04-30 | 2002-03-06 | University of Florida | Adeno-associated virus-delivered ribozyme compositions and methods of use |
| AU4671300A (en) * | 1999-04-30 | 2000-11-17 | City Of Hope | The use of adeno-associated virus (aav) deliver cytoprotective genes |
| US7829693B2 (en) * | 1999-11-24 | 2010-11-09 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of a target gene |
| US8546143B2 (en) | 2001-01-09 | 2013-10-01 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of a target gene |
| US20030003582A1 (en) * | 2001-05-08 | 2003-01-02 | Tranzyme, Inc. | Trans-viral vector mediated gene transfer to the retina |
| EP1495120B1 (en) | 2002-04-18 | 2012-10-10 | Acuity Pharmaceuticals, Inc | Means and methods for the specific modulation of target genes in the eye |
| US7148342B2 (en) | 2002-07-24 | 2006-12-12 | The Trustees Of The University Of Pennyslvania | Compositions and methods for sirna inhibition of angiogenesis |
| AU2003290586B2 (en) | 2002-11-04 | 2009-07-02 | University Of Massachusetts | Allele-specific RNA interference |
| US8680063B2 (en) | 2003-09-12 | 2014-03-25 | University Of Massachusetts | RNA interference for the treatment of gain-of-function disorders |
| EP1937066A4 (en) | 2005-08-18 | 2008-12-24 | Alnylam Pharmaceuticals Inc | METHOD AND COMPOSITIONS FOR THE TREATMENT OF NERVOUS DISEASES |
| EP2140004B1 (en) * | 2007-04-12 | 2022-01-12 | The Provost, Fellows, Foundation Scholars, & the other members of Board, of the College of the Holy & Undiv. Trinity of Queen Elizabeth near Dublin | Genetic suppression and replacement |
| AU2009322279A1 (en) | 2008-12-04 | 2011-07-14 | Opko Pharmaceuticals, Llc | Compositions and methods for selective inhibition of pro-angiogenic VEGF isoforms |
| WO2010127209A2 (en) * | 2009-04-30 | 2010-11-04 | The Research Foundation Of State University Of New York | Compositions and methods for therapy of macular degeneration |
| SG10201800541SA (en) | 2010-04-23 | 2018-03-28 | Univ Florida | Raav-guanylate cyclase compositions and methods for treating leber's congenital amaurosis-1 (lca1) |
| LT3137497T (lt) | 2014-05-02 | 2021-07-26 | Genzyme Corporation | Aav vektoriai, skirti tinklainės ir cns genų terapijai |
| EP4012035B1 (en) | 2014-09-16 | 2024-11-06 | Genzyme Corporation | Adeno-associated viral vectors for treating myocilin (myoc) glaucoma |
| PL4012035T3 (pl) | 2014-09-16 | 2025-03-24 | Genzyme Corporation | Wektory wirusowe związane z adenowirusami do leczenia jaskry miocylinowej (myoc) |
| AU2016222546B2 (en) | 2015-02-26 | 2020-01-23 | Ionis Pharmaceuticals, Inc. | Allele specific modulators of P23H rhodopsin |
| US11653636B2 (en) * | 2019-11-15 | 2023-05-23 | University Of Ulsan Foundation For Industry Cooperation | Method of making a rat model of retinal degeneration and rat model made thereby |
| EP4097121A1 (en) | 2020-01-29 | 2022-12-07 | Genzyme Corporation | Modified adeno-associated viral capsid proteins for ocular gene therapy and methods of use thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1997011169A2 (en) * | 1995-09-21 | 1997-03-27 | Provost, Fellows And Scholars Of The College Of The Holy And Undivided Trinity Of Queen Elizabeth Near Dublin | Strategy for suppressing the expression of an endogeneous gene by using compounds that are able to bind to the non-coding regions of the gene to be suppressed |
| AU7467598A (en) * | 1997-04-21 | 1998-11-13 | University Of Florida | Materials and methods for treatment of retinal diseases |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5116742A (en) | 1986-12-03 | 1992-05-26 | University Patents, Inc. | RNA ribozyme restriction endoribonucleases and methods |
| US4987071A (en) | 1986-12-03 | 1991-01-22 | University Patents, Inc. | RNA ribozyme polymerases, dephosphorylases, restriction endoribonucleases and methods |
| US5037746A (en) | 1986-12-03 | 1991-08-06 | University Patents, Inc. | RNA ribozyme polymerases, and methods |
| US5646020A (en) | 1992-05-14 | 1997-07-08 | Ribozyme Pharmaceuticals, Inc. | Hammerhead ribozymes for preferred targets |
| US5498539A (en) * | 1992-07-02 | 1996-03-12 | Daiichi Pharmaceutical Co., Ltd. | Bovine endothelial nitric oxide synthase nucleic acids |
| US5639655A (en) | 1993-01-19 | 1997-06-17 | Ribozyme Pharmaceuticals, Inc. | PML-RARA targeted ribozymes |
| US6410322B1 (en) | 1993-07-27 | 2002-06-25 | Hybridon Inc | Antisense oligonucleotide inhibition of vascular endothelial growth factor expression |
| US5646031A (en) | 1995-05-16 | 1997-07-08 | Northern Illinois University | SArMV and sCYMVI hairpin ribozymes |
| GB9604449D0 (en) | 1996-03-01 | 1996-05-01 | Farrar Gwyneth J | Genetic strategy ii |
| WO1998048009A2 (en) | 1997-04-21 | 1998-10-29 | University Of Florida | Materials and methods for ribozyme treatment of retinal diseases |
-
1998
- 1998-04-21 WO PCT/US1998/007968 patent/WO1998048009A2/en not_active Ceased
- 1998-04-21 CA CA002287508A patent/CA2287508A1/en not_active Abandoned
- 1998-04-21 BR BR9808606-5A patent/BR9808606A/pt not_active IP Right Cessation
- 1998-04-21 EP EP98918493A patent/EP0977841A2/en not_active Withdrawn
- 1998-04-21 AU AU71406/98A patent/AU735788B2/en not_active Ceased
- 1998-04-21 JP JP54625498A patent/JP2001523959A/ja not_active Ceased
- 1998-04-21 US US09/063,667 patent/US6225291B1/en not_active Expired - Lifetime
- 1998-04-21 NZ NZ500427A patent/NZ500427A/xx unknown
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1997011169A2 (en) * | 1995-09-21 | 1997-03-27 | Provost, Fellows And Scholars Of The College Of The Holy And Undivided Trinity Of Queen Elizabeth Near Dublin | Strategy for suppressing the expression of an endogeneous gene by using compounds that are able to bind to the non-coding regions of the gene to be suppressed |
| AU7467598A (en) * | 1997-04-21 | 1998-11-13 | University Of Florida | Materials and methods for treatment of retinal diseases |
Also Published As
| Publication number | Publication date |
|---|---|
| WO1998048009A3 (en) | 1999-03-25 |
| CA2287508A1 (en) | 1998-10-29 |
| AU7140698A (en) | 1998-11-13 |
| WO1998048009A2 (en) | 1998-10-29 |
| NZ500427A (en) | 2002-12-20 |
| EP0977841A2 (en) | 2000-02-09 |
| US6225291B1 (en) | 2001-05-01 |
| JP2001523959A (ja) | 2001-11-27 |
| BR9808606A (pt) | 2000-05-23 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU735788B2 (en) | Materials and methods for ribozyme treatment of diseases | |
| KR102670852B1 (ko) | 변이형 RNAi | |
| US7342111B2 (en) | Adeno-associated virus-delivered ribozyme compositions and methods of use | |
| KR101984145B1 (ko) | 레베르 선천성 흑내장-1(lca-1)의 치료를 위한 재조합 아데노-관련된 바이러스-구아닐레이트 사이클라제 조성물 및 방법 | |
| AU7467598A (en) | Materials and methods for treatment of retinal diseases | |
| US9255130B2 (en) | Puf-A and related compounds for treatment of retinopathies and sight-threatening ophthalmologic disorders | |
| Gorbatyuk et al. | Suppression of mouse rhodopsin expression in vivo by AAV mediated siRNA delivery | |
| WO2008154482A2 (en) | Sirna compositions and methods of use in treatment of ocular diseases | |
| JP2021534814A (ja) | アルファ−シヌクレインに対するバリアントＲＮＡｉ | |
| Gorbatyuk et al. | Knockdown of wild-type mouse rhodopsin using an AAV vectored ribozyme as part of an RNA replacement approach | |
| Hauswirth et al. | Ribozyme uses in retinal gene therapy | |
| EP1558291A2 (en) | rAAV-VECTORED RIBOZYME COMPOSITIONS AND METHODS FOR THE TREATMENT OF RETINAL DISEASES | |
| RU2763319C2 (ru) | Реагенты для лечения окулофарингеальной мышечной дистрофии (офмд) и их применение | |
| US20100041741A1 (en) | Suppression of mitochondrial oxidative stress | |
| CN112839682B (zh) | 用于治疗卵黄状黄斑变性的腺相关病毒载体 | |
| Flannery et al. | Ribozyme-mediated gene therapy for autosomal dominant retinal degeneration | |
| US20090068147A1 (en) | Raav vector-based pro-opiomelanocortin compositions and methods of use | |
| Liu et al. | Ribozyme knockdown of the γ-subunit of rod cGMP phosphodiesterase alters the ERG and retinal morphology in wild-type mice | |
| CA2659353C (en) | Composition and method for treatment of tumors | |
| WO2005084714A2 (en) | Raav-neprilysin compositions and methods of use | |
| EA046920B1 (ru) | Антисмысловые олигонуклеотиды, восстанавливающие аберрантный сплайсинг abca4 | |
| Nishikawa et al. | John G. Flannery, Alfred S. Lewin, 24 Kimberly A. Drenser, 2 | |
| Hauswirth et al. | Viral-vectored ribozymes as therapy for autosomal dominant retinal disease | |
| AU2002256409A1 (en) | Raav-vectored ribozyme compositions and methods for the treatment of rentinal diseases |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| SREP | Specification republished | ||
| FGA | Letters patent sealed or granted (standard patent) |