Management of chronic hepatitis B virus infection: a promising approach using small interfering RNA (siRNA).

ABSTRACT

Hepatitis B virus infection continues to be a major global health problem with an estimated 350 million carriers. The response to available treatment modalities is not impressive. The advent of RNA Interference--a phenomenon of sequence-specific degradation of RNAs mediated by double-stranded RNA--holds promise as a potential therapy for chronic hepatitis B virus infection. Synthetic preparations of short RNA (21-23 bp long) can be used to mediate this process of gene silencing with a lower immune response. The duration of suppression can be further increased by using a vector delivery system. Small interfering RNA (siRNA) has several advantages over conventional therapy, which include fewer side-effects, a lower chance of developing escape mutants and non-requirement of viral replication for its action. A potent knockdown of the gene of interest with high sequence specificity makes RNA interference a powerful tool that has shown antiviral effect against hepatitis B virus. However, the 'off-target effect', i.e. suppression of genes other than the intended target, poor siRNA stability, inefficient cellular uptake, widespread biodistribution and non-specific effects need to be overcome. The problem of long-term toxicity of siRNA should be addressed and an ideal vector delivery system needs to be designed before it can be put to clinical use.