With 387 million carriers of hepatitis B virus (HBV) and 170 million people persistently infected with hepatitis C virus (HCV), we need a solution. Treatments at present include the use of drugs, interferon and anti-viral agents but none of this is very effective. However, an article from the Journal of Viral Hepatitis published on August 13,2007 shows how the discovery of RNAi and the subsequent possibility to inhibit specific viral gene expression may prove to be the treatment for Chronic Hepatitis B and C.
Several studies cited in the article have shown the efficacy of the use of RNAi against HBV in mice models. An early study showed that the most effective sequence, which targeted a region of the surface and overlapping polymerase ORF, inhibited HBV surface antigen secretion by 94% in transfected cultured cells, and 85%in vivo in the MHI model. Other more recent studies have shown that a siRNA duplex that targeted sequence nucleotides 9-27 from the surface ORF initiation codon was found to be particularly effective against HBV without a requirement for HBV DNA synthesis. In the case of HCV although early on the main target of siRNA was the 5’NTR, no efficacy was observed in later studies. Significant inhibition of virus gene expression was achieved in replicon models when targeting NS3 and NS5B sequences.
Recent studies showed that modified long hairpin RNAs (lhRNAs) have been capable of silencing hepatitis C virus targets in cell culture. This interesting observation implies that by targeting a greater viral sequence, viral escape would be minimized. Using the lhRNA approach, silencing of multiple genotypes may be possible and the probability of effective silencing by one of the several lhRNA-derived siRNAs is likely to be improved.
The main issue with the use of drugs against viruses is that the development of drugs cannot cope with the mutations of the virus. With this new approach, however, this is not the case. According to the study even though the siRNA-resistant replicons showed point mutations within the siRNA target sequence, these resistant replicons were sensitive to an siRNA that targeted another part of the genome, suggesting that use of siRNA combinations limits evolution of escape mutants. The relative ease with which potent silencing of HBV and HCV sequences can be achieved using effectors of RNAi has led to considerable enthusiasm for developing this technology for therapeutic application. This therapy is however still under study. The main concerns are Immunostimulatory Effects of Short Interfering RNAs and Expressed Hairpin Sequences, Nonspecific Interaction of Silencing Molecules with Cellular Sequences and Regulating the Dosage and also method of delivery to the target. In spite of these difficulties there is a potential for the use of RNAi as a treatment against HCV and HBV and the next few years are likely to see considerable progress in this field.
For more information and a detailed look at the article check out the link below:
Opportunities for Treating Chronic Hepatitis B and C Virus Infection Using RNA Interference
http://www.medscape.com/viewarticle/560945
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ReplyDeleteRNAi is a characteristic interaction that works like a dimmer change to dial down the level of a protein. It probably evolved to shield cells from infections. The leeway of viral pathogens from an assortment of hosts is frequently the consequence of contaminated cells. A medicine containing a piece of the non-coding strand of courier RNA, a key molecule engaged with the interpretation of DNA into protein.
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