RNAi for Treating Hepatitis B Viral Infection
TLDR
Several strategies for improving the anti-HBV therapeutic efficacy of siRNAs, while avoiding their off-target effects and immunostimulation are discussed.Abstract:
Chronic hepatitis B virus (HBV) infection is one of the leading causes of liver cirrhosis and hepatocellular carcinoma (HCC). Current treatment strategies of HBV infection including the use of interferon (IFN)-α and nucleotide analogues such as lamivudine and adefovir have met with only partial success. Therefore, it is necessary to develop more effective antiviral therapies that can clear HBV infection with fewer side effects. RNA interference (RNAi), by which a small interfering RNA (siRNA) induces the gene silence at a post-transcriptional level, has the potential of treating HBV infection. The successful use of chemically synthesized siRNA, endogenous expression of small hairpin RNA (shRNA) or microRNA (miRNA) to silence the target gene make this technology towards a potentially rational therapeutics for HBV infection. However, several challenges including poor siRNA stability, inefficient cellular uptake, widespread biodistribution and non-specific effects need to be overcome. In this review, we discuss several strategies for improving the anti-HBV therapeutic efficacy of siRNAs, while avoiding their off-target effects and immunostimulation. There is an in-depth discussion on the (1) mechanisms of RNAi, (2) methods for siRNA/shRNA production, (3) barriers to RNAi-based therapies, and (4) delivery strategies of siRNA for treating HBV infection.read more
Citations
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Journal ArticleDOI
Hepatocyte-targeted RNAi Therapeutics for the Treatment of Chronic Hepatitis B Virus Infection
Christine I. Wooddell,David B. Rozema,Markus Hossbach,Matthias John,Holly Hamilton,Qili Chu,Julia Hegge,Jason Klein,Darren H. Wakefield,Claudia E. Oropeza,Jochen Deckert,Ingo Roehl,Kerstin Jahn-Hofmann,Philipp Hadwiger,Hans-Peter Vornlocher,Alan McLachlan,David L. Lewis +16 more
TL;DR: It is shown that a single coinjection of NAG-MLP with potent chol-siRNAs targeting conserved HBV sequences resulted in multilog repression of viral RNA, proteins, and viral DNA with long duration of effect.
Journal ArticleDOI
NF-κB signaling, liver disease and hepatoprotective agents
Beicheng Sun,Michael Karin +1 more
TL;DR: The NF-κB signaling pathway has particular relevance to several liver diseases including hepatitis, viral hepatitis induced by HBV and HCV, liver fibrosis and cirrhosis and hepatocellular carcinoma, and is a potential target for development of hepatoprotective agents.
Journal ArticleDOI
Present and future therapies of hepatitis B: From discovery to cure
T. Jake Liang,Timothy M. Block,Brian J. McMahon,Marc G. Ghany,Stephan Urban,Ju-Tao Guo,Stephen Locarnini,Fabien Zoulim,Kyong-Mi Chang,Anna S. Lok +9 more
TL;DR: The current state of science in HBV therapy is reviewed and new and exciting therapeutic strategies spurred by recent scientific advances are highlighted, bringing us closer to the possibility of a functional cure of chronic HBV infection.
Journal ArticleDOI
Nanoparticle-based delivery of small interfering RNA: challenges for cancer therapy.
Evelina Miele,Gian Paolo Spinelli,Ermanno Miele,Enzo Di Fabrizio,Elisabetta Ferretti,Silverio Tomao,Alberto Gulino +6 more
TL;DR: The main aims of this review are to explain the siRNA mechanism with regard to potential applications in siRNA-based cancer therapy; to discuss the possible usefulness of nanoparticle-based delivery of certain molecules for overcoming present therapeutic limitations; to review the ongoing relevant clinical research with its pitfalls and promises; and to evaluate critically future perspectives and challenges in si RNA- based cancer therapy.
Journal ArticleDOI
Non-Viral Nucleic Acid Delivery: Key Challenges and Future Directions
TL;DR: This review discusses some of the strategies that have been employed to overcome the barriers towards successful gene delivery, including cellular barriers, enzymatic degradation and rapid clearance after administration.
References
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