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Targeted inhibition of HBV gene expression by single‐chain antibody mediated small interfering RNA delivery
Author(s) -
Wen WeiHong,
Liu JiaYun,
Qin WeiJun,
Zhao Jing,
Wang Tao,
Jia LinTao,
Meng YanLing,
Gao Hui,
Xue CaiFang,
Jin BoQuan,
Yao LiBo,
Chen SiYi,
Yang AnGang
Publication year - 2007
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.21663
Subject(s) - small interfering rna , virology , rna , antibody , gene expression , microbiology and biotechnology , gene , biology , genetics
RNA interference is highly effective at inhibiting HBV gene expression and replication. However, before small interfering RNA (siRNA) can be used in the clinic, it is essential to develop a system to target their delivery. Antibody‐mediated delivery is a novel approach for targeting siRNA to appropriate cells. In this report, we asked whether this siRNA delivery strategy would be effective against HBV. Of 5 candidates, a specific siRNA that effectively inhibited HBV gene expression and replication was determined. Two fusion proteins, s‐tP and sCκ‐tP, were constructed to contain a single chain of the human variable fragment, scFv, against hepatitis B surface antigen (HBsAg), a truncated protamine (tP), and in the case of sCκ‐tP, a constant region of the κ chain (Cκ). S‐tP and sCκ‐tP were developed to provide targeted delivery of the siRNA, siRNA expressing cassettes (SEC), and siRNA‐producing plasmids. Fluorescein isothiocyanate‐siRNA, fluorescein isothiocyanate‐SEC, and plasmid DNA were specifically delivered into HBsAg‐positive cells using the sCκ‐tP fusion protein, and effectively inhibited HBV gene expression and replication. HBV gene expression was also inhibited by siRNA or siRNA‐producing plasmids in HBV transgenic mice. Conclusion: Our results describe a potential method for the targeted delivery of siRNA or siRNA‐producing plasmids against HBV, using anti‐HBsAg fusion proteins. (H EPATOLOGY 2007;46:84–94.)