These authors contributed euqally to this work.
Targeted inhibition of HBV gene expression by single-chain antibody mediated small interfering RNA delivery†
Article first published online: 27 JUN 2007
Copyright © 2007 American Association for the Study of Liver Diseases
Volume 46, Issue 1, pages 84–94, July 2007
How to Cite
Wen, W.-H., Liu, J.-Y., Qin, W.-J., Zhao, J., Wang, T., Jia, L.-T., Meng, Y.-L., Gao, H., Xue, C.-F., Jin, B.-Q., Yao, L.-B., Chen, S.-Y. and Yang, A.-G. (2007), Targeted inhibition of HBV gene expression by single-chain antibody mediated small interfering RNA delivery. Hepatology, 46: 84–94. doi: 10.1002/hep.21663
Potential conflict of interest: Nothing to report.
- Issue published online: 27 JUN 2007
- Article first published online: 27 JUN 2007
- Manuscript Accepted: 8 JAN 2007
- Manuscript Received: 27 NOV 2006
- National Basic Research Program of China. Grant Number: 2004CB518805
- Program for Changjiang Scholars and Innovative Research Team in University. Grant Number: IRT0459
- National Natural Science Foundation of China. Grant Numbers: 30400403, 30500433
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. (HEPATOLOGY 2007;46:84–94.)