RNAi for treating hepatitis B viral infection

Yong Chen, Guofeng Cheng, Ram I Mahato

Research output: Contribution to journalReview article

93 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)72-86
Number of pages15
JournalPharmaceutical Research
Volume25
Issue number1
DOIs
StatePublished - Jan 1 2008

Fingerprint

Virus Diseases
RNA Interference
Hepatitis B
Viruses
Hepatitis B virus
Small Interfering RNA
RNA
Genes
Therapeutics
Lamivudine
RNA Stability
Chronic Hepatitis B
MicroRNAs
Liver Cirrhosis
Liver
Interferons
Antiviral Agents
Hepatocellular Carcinoma
Immunization
Nucleotides

Keywords

  • Bioconjugation
  • Chemical modification
  • Gene silencing
  • Hepatitis B virus
  • RNAi
  • siRNA

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)

Cite this

RNAi for treating hepatitis B viral infection. / Chen, Yong; Cheng, Guofeng; Mahato, Ram I.

In: Pharmaceutical Research, Vol. 25, No. 1, 01.01.2008, p. 72-86.

Research output: Contribution to journalReview article

Chen, Yong ; Cheng, Guofeng ; Mahato, Ram I. / RNAi for treating hepatitis B viral infection. In: Pharmaceutical Research. 2008 ; Vol. 25, No. 1. pp. 72-86.
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