JP2007527244A5 - - Google Patents
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- JP2007527244A5 JP2007527244A5 JP2007502094A JP2007502094A JP2007527244A5 JP 2007527244 A5 JP2007527244 A5 JP 2007527244A5 JP 2007502094 A JP2007502094 A JP 2007502094A JP 2007502094 A JP2007502094 A JP 2007502094A JP 2007527244 A5 JP2007527244 A5 JP 2007527244A5
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- Prior art keywords
- rnai
- nucleic acid
- promoter
- sequence
- seq
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- 230000025458 RNA interference Effects 0.000 claims description 21
- 229920001850 Nucleic acid sequence Polymers 0.000 claims description 5
- 230000003612 virological Effects 0.000 claims description 4
- 230000035772 mutation Effects 0.000 claims description 3
- 230000002401 inhibitory effect Effects 0.000 claims description 2
- 241000894007 species Species 0.000 claims 9
- 150000007523 nucleic acids Chemical group 0.000 claims 8
- 230000002068 genetic Effects 0.000 claims 7
- 108020004707 nucleic acids Proteins 0.000 claims 5
- 241000711549 Hepacivirus C Species 0.000 claims 3
- 239000003814 drug Substances 0.000 claims 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- 238000004806 packaging method and process Methods 0.000 claims 2
- 239000002245 particle Substances 0.000 claims 2
- 239000004480 active ingredient Substances 0.000 claims 1
- 241000700605 Viruses Species 0.000 description 2
- 206010047461 Viral infection Diseases 0.000 description 1
- 208000001756 Virus Disease Diseases 0.000 description 1
- 230000000840 anti-viral Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000017613 viral reproduction Effects 0.000 description 1
Description
現在の抗ウイルス療法の主要な問題は、エスケープ変異体として一般に知られる耐性変異体の出現である（Gitlin et. al. J. of Virol. 79; 1027-1035, (2005)）。本発明の一つの側面は、エスケープ変異体の出現を中和する。本発明の幾つかの実施態様において、ウイルス感染を治療するための多重RNAi配列の選択は、単一配列のRNAiを用いた感染細胞の治療からのエスケープ変異体の出現に基づいている。出現するエスケープ変異体は、細胞がウイルスに感染した後のRNAiの単一配列を含む発現構築物を用いた治療によって明らかになる。出現した耐性ウイルスを含んだ細胞が回収され、ウイルスゲノムの配列が決定される。配列決定によって、ウイルス阻害に抵抗するように生じた支配的な変異が明らかになる。標的遺伝子の遺伝配列に基づくRNAi配列を含み、更にRNAi治療に抵抗するように生じた点変異の配列に基づくRNAi配列を含んだ、本発明のマルチプロモーターRNAi発現構築物が作製される。
Claims (11)
- 少なくとも３つのプロモーター／RNAi／ターミネーター構成要素を含むマルチプロモーター発現カセットを含む遺伝子構築物であって、前記各プロモーター／RNAi／ターミネーター構成要素がプロモ−ター、ターミネーターおよび前記プロモーターおよびターミネーターに機能的に連結されたRNAi種をコードする配列含み、前記RNAi種の少なくとも一つが配列番号２２によってコードされている、前記遺伝子構築物。
- RNAi種の少なくとも一つが配列番号６または配列番号１９によってコードされている、請求項1記載の遺伝子構築物。
- RNAi種が配列番号６、配列番号１９および配列番号２２によってコードされている、請求項1記載の遺伝子構築物。
- プロモーター／RNAi／ターミネーター構成要素中のターミネーターのうちの２つの配列が互いに異なっている、請求項１〜３のいずれか1項記載の遺伝子構築物。
- プロモーター／RNAi／ターミネーター構成要素中のプロモーターのうちの２つの配列が互いに異なっている、請求項１〜４のいずれか1項記載の遺伝子構築物。
- ３つ以上のRNAi種が変種間で単一ヌクレオチド配列多型(SNPs)を有する核酸配列を標的とし、前記RNAi種の各々が前記変種の一以上のサブセットを標的とし得る、請求項１〜５のいずれか1項記載の遺伝子構築物。
- RNAi種の配列が、核酸配列の一以上の変種を標的とする、請求項１〜５のいずれか1項記載の遺伝子構築物。
- RNAi種が標的核酸配列に基づき、さらにRNAi治療に抵抗するように生じた点変異を有する配列に基づく、請求項１記載の遺伝子構築物。
- 細胞中で発現している１以上のＣ型肝炎ウイルス核酸標的を阻害するための組成物であって、請求項１〜８のいずれか1項記載の遺伝子構築物を活性成分として含み、各RNAi種が前記核酸標的の配列または前記核酸標的の変種の配列と実質的に同一である、前記組成物。
- 細胞中で発現している１以上のＣ型肝炎ウイルス核酸標的の発現を改変するための医薬の製造のための請求項１〜８のいずれか1項記載の遺伝子構築物の使用であって、
請求項１〜８のいずれか1項記載の遺伝子構築物をウイルス粒子にパッケージングすること、
を含む、前記使用。 - 細胞中で発現している１以上のＣ型肝炎ウイルス核酸標的の発現を改変するための医薬の製造のための請求項１〜８のいずれか1項記載の遺伝子構築物の使用であって、
請求項１〜８のいずれか1項記載の遺伝子構築物を非ウイルス粒子にパッケージングすること、
を含む、前記使用。
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US55050404P | 2004-03-05 | 2004-03-05 | |
| US60/550,504 | 2004-03-05 | ||
| US55392004P | 2004-03-17 | 2004-03-17 | |
| US60/553,920 | 2004-03-17 | ||
| PCT/US2005/007447 WO2005087926A2 (en) | 2004-03-05 | 2005-03-04 | Multiple promoter expression cassettes for simultaneous delivery of rnai agents |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2007527244A JP2007527244A (ja) | 2007-09-27 |
| JP2007527244A5 true JP2007527244A5 (ja) | 2011-06-02 |
| JP4763681B2 JP4763681B2 (ja) | 2011-08-31 |
Family
ID=34963938
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2007502094A Expired - Fee Related JP4763681B2 (ja) | 2004-03-05 | 2005-03-04 | ＲＮＡｉ作用媒介物の同時デリバリーのためのマルチプロモーター発現カセット |
Country Status (13)
| Country | Link |
|---|---|
| US (3) | US7727970B2 (ja) |
| EP (2) | EP2363483A3 (ja) |
| JP (1) | JP4763681B2 (ja) |
| KR (2) | KR101337579B1 (ja) |
| CN (1) | CN103060324B (ja) |
| AT (1) | ATE508190T1 (ja) |
| AU (1) | AU2005222084B2 (ja) |
| CA (1) | CA2558771C (ja) |
| DE (1) | DE602005027820D1 (ja) |
| DK (1) | DK1725660T3 (ja) |
| IL (1) | IL177862A (ja) |
| NZ (1) | NZ550284A (ja) |
| WO (1) | WO2005087926A2 (ja) |
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| CN1276976C (zh) | 2003-10-30 | 2006-09-27 | 封江南 | 单一载体编码多个发夹结构小干扰性rna表达系统及其构建方法 |
| ATE508190T1 (de) * | 2004-03-05 | 2011-05-15 | Benitec Inc | Mehrfachpromotor-expressionskassetten zurgleichzeitigen zuführung von rnai-agentien |
| CN101068926B (zh) * | 2004-03-05 | 2013-01-02 | 贝尼泰克生物制药有限公司 | 用于RNAi试剂同时递送的多启动子表达盒及用途 |
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2005
- 2005-03-04 AT AT05727680T patent/ATE508190T1/de not_active IP Right Cessation
- 2005-03-04 NZ NZ550284A patent/NZ550284A/en unknown
- 2005-03-04 EP EP11161216.4A patent/EP2363483A3/en not_active Withdrawn
- 2005-03-04 US US11/072,592 patent/US7727970B2/en not_active Expired - Fee Related
- 2005-03-04 EP EP05727680A patent/EP1725660B1/en not_active Not-in-force
- 2005-03-04 WO PCT/US2005/007447 patent/WO2005087926A2/en active Application Filing
- 2005-03-04 KR KR1020127000533A patent/KR101337579B1/ko not_active IP Right Cessation
- 2005-03-04 DE DE602005027820T patent/DE602005027820D1/de active Active
- 2005-03-04 JP JP2007502094A patent/JP4763681B2/ja not_active Expired - Fee Related
- 2005-03-04 AU AU2005222084A patent/AU2005222084B2/en not_active Ceased
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- 2005-03-04 CN CN201210556628.0A patent/CN103060324B/zh not_active Expired - Fee Related
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2010
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