JP2008514242A5 - - Google Patents
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- JP2008514242A5 JP2008514242A5 JP2007534866A JP2007534866A JP2008514242A5 JP 2008514242 A5 JP2008514242 A5 JP 2008514242A5 JP 2007534866 A JP2007534866 A JP 2007534866A JP 2007534866 A JP2007534866 A JP 2007534866A JP 2008514242 A5 JP2008514242 A5 JP 2008514242A5
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- sirna
- sirna molecule
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- molecule
- modified
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- 239000002924 silencing RNA Substances 0.000 claims description 57
- 108020004459 Small Interfering RNA Proteins 0.000 claims description 53
- 125000002652 ribonucleotide group Chemical group 0.000 claims description 7
- HVYWMOMLDIMFJA-DPAQBDIFSA-N (3β)-Cholest-5-en-3-ol 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 claims description 6
- 229920001914 Ribonucleotide Polymers 0.000 claims description 6
- 239000002336 ribonucleotide Substances 0.000 claims description 6
- 229940107161 Cholesterol Drugs 0.000 claims description 3
- 229920001850 Nucleic acid sequence Polymers 0.000 claims description 3
- 235000012000 cholesterol Nutrition 0.000 claims description 3
- 150000003230 pyrimidines Chemical class 0.000 claims description 3
- 230000002401 inhibitory effect Effects 0.000 claims description 2
- 230000004048 modification Effects 0.000 claims 13
- 238000006011 modification reaction Methods 0.000 claims 13
- 230000027455 binding Effects 0.000 claims 10
- 239000003446 ligand Substances 0.000 claims 5
- 102000005962 receptors Human genes 0.000 claims 5
- 108020003175 receptors Proteins 0.000 claims 5
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 claims 3
- CZPWVGJYEJSRLH-UHFFFAOYSA-N 289-95-2 Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims 2
- OPTASPLRGRRNAP-UHFFFAOYSA-N Cytosine Chemical group NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 claims 2
- 125000001153 fluoro group Chemical group F* 0.000 claims 2
- 229940104302 Cytosine Drugs 0.000 claims 1
- 102000007330 LDL Lipoproteins Human genes 0.000 claims 1
- 108010007622 LDL Lipoproteins Proteins 0.000 claims 1
- 102000006382 Ribonucleases Human genes 0.000 claims 1
- 108010083644 Ribonucleases Proteins 0.000 claims 1
- 229940035893 Uracil Drugs 0.000 claims 1
- 239000000427 antigen Substances 0.000 claims 1
- 102000038129 antigens Human genes 0.000 claims 1
- 108091007172 antigens Proteins 0.000 claims 1
- 230000015556 catabolic process Effects 0.000 claims 1
- 230000004059 degradation Effects 0.000 claims 1
- 238000006731 degradation reaction Methods 0.000 claims 1
- XOBKSJJDNFUZPF-UHFFFAOYSA-N methoxyethyl Chemical group CCOC XOBKSJJDNFUZPF-UHFFFAOYSA-N 0.000 claims 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 1
- 125000003729 nucleotide group Chemical group 0.000 claims 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
- 230000029812 viral genome replication Effects 0.000 claims 1
- 210000004027 cells Anatomy 0.000 description 13
- 229920000160 (ribonucleotides)n+m Polymers 0.000 description 10
- 239000005089 Luciferase Substances 0.000 description 9
- 108060001084 Luciferase family Proteins 0.000 description 9
- 230000000694 effects Effects 0.000 description 9
- 230000001965 increased Effects 0.000 description 5
- 101710037135 GAPC2 Proteins 0.000 description 4
- 101710037116 GAPC3 Proteins 0.000 description 4
- 101710025049 GAPDG Proteins 0.000 description 4
- 101710008404 GAPDH Proteins 0.000 description 4
- 102100006425 GAPDH Human genes 0.000 description 4
- 101710010461 Gapdh1 Proteins 0.000 description 4
- 229920001681 Heteroduplex Polymers 0.000 description 4
- 101710025050 MK0970 Proteins 0.000 description 4
- 101710025091 cbbGC Proteins 0.000 description 4
- 231100000673 dose–response relationship Toxicity 0.000 description 4
- 101710025070 gapdh-2 Proteins 0.000 description 4
- 210000002966 Serum Anatomy 0.000 description 3
- 230000003247 decreasing Effects 0.000 description 3
- 230000001939 inductive effect Effects 0.000 description 3
- 238000003670 luciferase enzyme activity assay Methods 0.000 description 3
- WAVYAFBQOXCGSZ-UHFFFAOYSA-N 2-fluoropyrimidine Chemical group FC1=NC=CC=N1 WAVYAFBQOXCGSZ-UHFFFAOYSA-N 0.000 description 2
- 102000034451 ATPases Human genes 0.000 description 2
- 108091006096 ATPases Proteins 0.000 description 2
- 210000003494 Hepatocytes Anatomy 0.000 description 2
- 210000004185 Liver Anatomy 0.000 description 2
- 102100011960 MIR7-3HG Human genes 0.000 description 2
- 101710008473 MIR7-3HG Proteins 0.000 description 2
- 230000025458 RNA interference Effects 0.000 description 2
- 241000315672 SARS coronavirus Species 0.000 description 2
- 108091006028 chimera Proteins 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 238000001890 transfection Methods 0.000 description 2
- 241000255581 Drosophila <fruit fly, genus> Species 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000331 Firefly luciferases Proteins 0.000 description 1
- 206010073071 Hepatocellular carcinoma Diseases 0.000 description 1
- 229920001320 Leader sequence (mRNA) Polymers 0.000 description 1
- 108020004999 Messenger RNA Proteins 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 238000003149 assay kit Methods 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 229920003013 deoxyribonucleic acid Polymers 0.000 description 1
- 239000005547 deoxyribonucleotide Substances 0.000 description 1
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000003682 fluorination reaction Methods 0.000 description 1
- 230000034659 glycolysis Effects 0.000 description 1
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 229920002106 messenger RNA Polymers 0.000 description 1
- 230000002588 toxic Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
Description
2つの例示的な改変型siRNA(順に、配列番号5および配列番号6)を以下に示す:
Claims (18)
- 改変型リボヌクレオチドを含むsiRNA分子であって、該siRNAは、
(a)その3’末端に2塩基デオキシヌクレオチド「TT」配列を含み、
(b)RNアーゼに対して耐性であり、
(c)ウイルス複製を阻害し得る、
siRNA分子。 - 前記siRNA分子が2’改変されている、請求項1に記載のsiRNA分子。
- 前記2’改変が、フルオロ改変、メチル改変、メトキシエチル改変、およびプロピル改変からなる群より選択される、請求項2に記載のsiRNA分子。
- 前記フルオロ改変が、2’−フルオロ改変または2’,2’−フルオロ改変である、請求項3に記載のsiRNA分子。
- 前記siRNAの少なくとも1つのピリミジンが改変されており、該ピリミジンは、シトシン、シトシンの誘導体、ウラシル、またはウラシルの誘導体である、請求項4に記載のsiRNA分子。
- 前記siRNA中のピリミジンすべてが改変されている、請求項5に記載のsiRNA分子。
- 前記siRNAの両方の鎖が、少なくとも1つの改変型ヌクレオチドを含む、請求項1に記載のsiRNA分子。
- 前記siRNAが、約10個〜約30個のリボヌクレオチドからなる、請求項1に記載のsiRNA分子。
- 前記siRNAが、約19個〜約23個のリボヌクレオチドからなる、請求項8に記載のsiRNA分子。
- HCVの複製を阻害する、請求項1に記載のsiRNA分子。
- siRNA5、siRNAC1、siRNAC2、siRNA5B1、siRNA5B2、またはsiRNA5B4のヌクレオチド配列と少なくとも80%同一であるヌクレオチド配列を含む、請求項10に記載のsiRNA分子。
- 少なくとも1つのレセプター結合リガンドに連結されている、請求項10に記載のsiRNA分子。
- 前記レセプター結合リガンドが、前記siRNA分子の5’末端または3’末端に結合されている、請求項12に記載のsiRNA分子。
- 前記レセプター結合リガンドが前記siRNA分子の複数の末端に結合されている、請求項13に記載のsiRNA分子。
- 前記レセプター結合リガンドが、コレステロール、HBV表面抗原、および低密度リポタンパク質からなる群より選択される、請求項12に記載のsiRNA分子。
- 前記レセプター結合リガンドがコレステロールである、請求項15に記載のsiRNA分子。
- 少なくとも1つのリボヌクレオチドの2’位改変
をさらに含み、該少なくとも1つのリボヌクレオチドの2’位改変によって前記siRNAが分解に対して耐性になっている、
請求項12に記載のsiRNA分子。 - 前記少なくとも1つのリボヌクレオチドの2’位改変が、2’−フルオロ改変または2’,2’−フルオロ改変である、請求項17に記載のsiRNA分子。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US61495504P | 2004-10-01 | 2004-10-01 | |
PCT/US2005/035493 WO2006039656A2 (en) | 2004-10-01 | 2005-09-30 | Modified small interfering rna molecules and methods of use |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2012054494A Division JP2012105686A (ja) | 2004-10-01 | 2012-03-12 | 改変型の小さい干渉rna分子および使用方法 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2008514242A JP2008514242A (ja) | 2008-05-08 |
JP2008514242A5 true JP2008514242A5 (ja) | 2008-10-02 |
Family
ID=36143139
Family Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2007534866A Pending JP2008514242A (ja) | 2004-10-01 | 2005-09-30 | 改変型の小さい干渉rna分子および使用方法 |
JP2012054494A Pending JP2012105686A (ja) | 2004-10-01 | 2012-03-12 | 改変型の小さい干渉rna分子および使用方法 |
JP2012193264A Pending JP2012255024A (ja) | 2004-10-01 | 2012-09-03 | 改変型の小さい干渉rna分子および使用方法 |
Family Applications After (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2012054494A Pending JP2012105686A (ja) | 2004-10-01 | 2012-03-12 | 改変型の小さい干渉rna分子および使用方法 |
JP2012193264A Pending JP2012255024A (ja) | 2004-10-01 | 2012-09-03 | 改変型の小さい干渉rna分子および使用方法 |
Country Status (6)
Country | Link |
---|---|
US (1) | US8138161B2 (ja) |
EP (1) | EP1796732B1 (ja) |
JP (3) | JP2008514242A (ja) |
CA (1) | CA2581651C (ja) |
ES (1) | ES2441791T3 (ja) |
WO (1) | WO2006039656A2 (ja) |
Families Citing this family (22)
Publication number | Priority date | Publication date | Assignee | Title |
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US10131904B2 (en) | 2008-02-11 | 2018-11-20 | Rxi Pharmaceuticals Corporation | Modified RNAi polynucleotides and uses thereof |
WO2010008582A2 (en) | 2008-07-18 | 2010-01-21 | Rxi Pharmaceuticals Corporation | Phagocytic cell drug delivery system |
JP2012502991A (ja) | 2008-09-22 | 2012-02-02 | アールエックスアイ ファーマシューティカルズ コーポレーション | 皮膚適用におけるrna干渉 |
WO2010059226A2 (en) | 2008-11-19 | 2010-05-27 | Rxi Pharmaceuticals Corporation | Inhibition of map4k4 through rnai |
US9493774B2 (en) | 2009-01-05 | 2016-11-15 | Rxi Pharmaceuticals Corporation | Inhibition of PCSK9 through RNAi |
WO2010090762A1 (en) | 2009-02-04 | 2010-08-12 | Rxi Pharmaceuticals Corporation | Rna duplexes with single stranded phosphorothioate nucleotide regions for additional functionality |
WO2011119871A1 (en) | 2010-03-24 | 2011-09-29 | Rxi Phrmaceuticals Corporation | Rna interference in ocular indications |
WO2011119852A1 (en) | 2010-03-24 | 2011-09-29 | Rxi Pharmaceuticals Corporation | Reduced size self-delivering rnai compounds |
BR112012024049A2 (pt) | 2010-03-24 | 2017-03-01 | Rxi Pharmaceuticals Corp | interferência de rna em indicações dérmicas e fibróticas |
RU2624045C2 (ru) * | 2010-08-17 | 2017-06-30 | Сирна Терапьютикс,Инк | ОПОСРЕДУЕМОЕ РНК-ИНТЕРФЕРЕНЦИЕЙ ИНГИБИРОВАНИЕ ЭКСПРЕССИИ ГЕНОВ ВИРУСА ГЕПАТИТА B (HBV) С ПРИМЕНЕНИЕМ МАЛОЙ ИНТЕРФЕРИРУЮЩЕЙ НУКЛЕИНОВОЙ КИСЛОТЫ (миНК) |
RU2744194C2 (ru) | 2013-12-02 | 2021-03-03 | Фио Фармасьютикалс Корп | Иммунотерапия рака |
CA2947270A1 (en) | 2014-04-28 | 2015-11-05 | Rxi Pharmaceuticals Corporation | Methods for treating cancer using nucleic acids targeting mdm2 or mycn |
US10900039B2 (en) | 2014-09-05 | 2021-01-26 | Phio Pharmaceuticals Corp. | Methods for treating aging and skin disorders using nucleic acids targeting Tyr or MMP1 |
GB201418135D0 (en) * | 2014-10-14 | 2014-11-26 | London School Hygiene & Tropical Medicine | Anti-viral agent |
CN108135923B (zh) | 2015-07-06 | 2021-03-02 | 菲奥医药公司 | 靶向超氧化物歧化酶1(sod1)的核酸分子 |
WO2017007825A1 (en) | 2015-07-06 | 2017-01-12 | Rxi Pharmaceuticals Corporation | Methods for treating neurological disorders using a synergistic small molecule and nucleic acids therapeutic approach |
US20170016000A1 (en) | 2015-07-17 | 2017-01-19 | Arcturus Therapeutics, Inc. | Compositions and agents against hepatitis b virus and uses thereof |
US20170137821A1 (en) | 2015-07-17 | 2017-05-18 | Arcturus Therapeutics, Inc. | Molecules and agents for treating hepatitis b virus |
JP2018531037A (ja) | 2015-10-19 | 2018-10-25 | アールエックスアイ ファーマシューティカルズ コーポレーション | 長い非コードrnaを標的とする減少したサイズの自己送達型核酸化合物 |
AU2017368050A1 (en) | 2016-11-29 | 2019-06-20 | Puretech Lyt, Inc. | Exosomes for delivery of therapeutic agents |
WO2019014359A2 (en) * | 2017-07-12 | 2019-01-17 | The Scripps Research Institute | POLYMERASE CHAIN TRANSCRIPTION (PCT): EXPONENTIAL SYNTHESIS OF RNA AND MODIFIED RNA |
US11425125B2 (en) * | 2020-06-24 | 2022-08-23 | Google Llc | Shared resource identification |
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US20030206887A1 (en) * | 1992-05-14 | 2003-11-06 | David Morrissey | RNA interference mediated inhibition of hepatitis B virus (HBV) using short interfering nucleic acid (siNA) |
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-
2005
- 2005-09-30 US US11/664,008 patent/US8138161B2/en not_active Expired - Fee Related
- 2005-09-30 EP EP05808592.9A patent/EP1796732B1/en not_active Not-in-force
- 2005-09-30 CA CA2581651A patent/CA2581651C/en not_active Expired - Fee Related
- 2005-09-30 JP JP2007534866A patent/JP2008514242A/ja active Pending
- 2005-09-30 ES ES05808592.9T patent/ES2441791T3/es active Active
- 2005-09-30 WO PCT/US2005/035493 patent/WO2006039656A2/en active Application Filing
-
2012
- 2012-03-12 JP JP2012054494A patent/JP2012105686A/ja active Pending
- 2012-09-03 JP JP2012193264A patent/JP2012255024A/ja active Pending
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