Harnessing RNAi for the Treatment of Viral Infections
Lorea Blazquez and Puri Fortes
from: Applied RNAi: From Fundamental Research to Therapeutic Applications (Edited by: Patrick Arbuthnot and Marc S. Weinberg). Caister Academic Press, U.K. (2014)
No treatment currently exists for many devastating viral infections. These include infections with emerging viruses or with viruses such as influenza that change very rapidly. Other viral infections can be treated, but the therapies may exert damaging unwanted side effects. Moreover, many viruses may evolve easily to drug resistant variants. Therefore, development of novel therapies for the treatment of viral infections is mandatory. RNA interference (RNAi) is a widely used technique to inhibit gene expression with a tremendous potential as an antiviral. Since RNAi degrades RNA in a sequence-specific manner, the only requirement for the development of RNAi inhibitors is to know the sequence of the target gene or the viral genome. Furthermore, host cell factors that are essential for viral infection but dispensable for cell viability, can be easily identified with genome-wide screenings and targeted by RNAi. The combination of different RNAi inhibitors, or the combination of RNAi with alternative therapies, should avoid the emergence of escape mutants resistant to the treatment. Over the last decade, several studies have used synthetic or gene-expressed short-interfering RNAs (siRNAs) to treat viral infections. Despite promising results in preclinical models, translation to clinical trials has been slow. Delivery remains the main challenge for the therapeutic application of RNAi. Several chemical formulations have been developed that increase delivery, stability and specificity of synthetic RNAi inhibitors or that target them to a specific organ. Several viral and non viral vectors have been employed to increase the delivery or the targeting of gene-expressed siRNAs. However, further efforts to improve delivery and decrease unwanted side effects of RNAi are still required. In the present review we discuss the current status of RNAi as an antiviral for the treatment of viral hepatitis, haemorrhagic fever viruses, respiratory viruses and other viruses read more ...