Management of chronic hepatitis B virus infection: a promising approach using small interfering RNA (siRNA).
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.
Dwivedi
Manisha
M
Department of Gastroenterology, Moti Lal Nehru Medical College, University of Allahabad, Allahabad, Uttar Pradesh, India. manisha_dwivedi@hotmail.com
Misra
S P
SP
Misra
Vatsala
V
Waikhom
R K
RK
Bhatnagar
Mukti
M
D020868:Gene Silencing; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors; D019694:Hepatitis B, Chronic / Q000628:therapy*; D006801:Humans; D034622:RNA Interference; D012330:RNA, Double-Stranded; D034741:RNA, Small Interfering / Q000009:adverse effects / Q000627:therapeutic use*
D012330:RNA, Double-Stranded; D034741:RNA, Small Interfering