Research abstract
Article abstract
Nature Biotechnology 26, 431 - 442 (2008)
Published online: 30 March 2008 | doi:10.1038/nbt1396
Resolution of liver cirrhosis using vitamin A–coupled liposomes to deliver siRNA against a collagen-specific chaperone
Yasushi Sato1,2, Kazuyuki Murase1,2, Junji Kato1,2, Masayoshi Kobune1, Tsutomu Sato1, Yutaka Kawano1, Rishu Takimoto1, Kouichi Takada1, Koji Miyanishi1, Takuya Matsunaga1, Tetsuji Takayama1 & Yoshiro Niitsu1
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 CCl4 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.
- Fourth Department of Internal Medicine, Sapporo Medical University, School of Medicine, Sapporo, 060-8543, Japan.
- These authors contributed equally to this work.
Correspondence to: Yoshiro Niitsu1 e-mail: niitsu@sapmed.ac.jp
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