論文 - 詳細
| RRC ID | 4594 |
|---|---|
| 著者 | Sato Y, Murase K, Kato J, Kobune M, Sato T, Kawano Y, Takimoto R, Takada K, Miyanishi K, Matsunaga T, Takayama T, Niitsu Y. |
| タイトル | Resolution of liver cirrhosis using vitamin A-coupled liposomes to deliver siRNA against a collagen-specific chaperone. |
| ジャーナル | Nat Biotechnol |
| Abstract |
There are currently no approved antifibrotic therapies for liver cirrhosis. We used vitamin A-coupled liposomes to deliver small interfering RNA (siRNA) against gp46, the rat homolog of human heat shock protein 47, to hepatic stellate cells. Our approach exploits the key roles of these cells in both fibrogenesis as well as uptake and storage of vitamin A. Five treatments with the siRNA-bearing vitamin A-coupled liposomes almost completely resolved liver fibrosis and prolonged survival in rats with otherwise lethal dimethylnitrosamine-induced liver cirrhosis in a dose- and duration-dependent manner. Rescue was not related to off-target effects or associated with recruitment of innate immunity. Receptor-specific siRNA delivery was similarly effective in suppressing collagen secretion and treating fibrosis induced by CCl(4) or bile duct ligation. The efficacy of the approach using both acute and chronic models of liver fibrosis suggests its therapeutic potential for reversing human liver cirrhosis. |
| 巻・号 | 26(4) |
| ページ | 431-42 |
| 公開日 | 2008-4-1 |
| DOI | 10.1038/nbt1396 |
| PII | nbt1396 |
| PMID | 18376398 |
| MeSH | Animals Collagen / genetics* Drug Carriers / chemistry Gene Targeting / methods* Genetic Therapy / methods* Humans Liposomes / chemistry* Liver Cirrhosis / genetics Liver Cirrhosis / therapy* Molecular Chaperones / genetics RNA, Small Interfering / genetics RNA, Small Interfering / therapeutic use* Rats Treatment Outcome Vitamin A / administration & dosage* |
| IF | 36.553 |
| 引用数 | 344 |
| WOS 分野 | BIOTECHNOLOGY & APPLIED MICROBIOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | NRK(RCB0043) |