Therapeutic Approaches of Viral Gene Silencing by Small Interfering RNA: Strategies to Prevent the Emergence of Antiviral Resistant Escape Mutants.

RNA interference (RNAi) was originally regarded as a mechanism of eukaryotic post-transcriptional gene regulation mediated by small interfering RNA (siRNA)-induced sequence-specific RNA degradation. It is well known to exert as an important antiviral defense mechanism in a wide range of organisms, from plants to invertebrates. The specificity, ease of design, and ability to target conserved gene regions make siRNA technology a promising approach to combat viral pathogenesis, allowing the targeting of multiple virus strains. The mechanism of sequence complementarity utilized by siRNAs against their targets presents a novel strategy to combat viral infections, as they can specifically target and degrade viral RNA. Consequently, siRNA-based therapeutics have been applied to various viral diseases. This is largely due to the design flexibility and rapid response potential of RNAi technologies, which provide advantages over traditional antiviral agents. However, the emergence of viral escape mutants poses a major barrier to the sustained antiviral activity of siRNA-based therapy. Therefore, devising strategies to overcome the emergence of escape mutants to antiviral siRNAs could enhance the efficacy of siRNA-based therapeutics in providing a rapid response to emerging viral infectious diseases. This review aims to comprehensively summarize the current knowledge on siRNA-based therapeutic approaches against viral infections and elucidate the challenges associated with implementing siRNA treatment, with a specific emphasis on antiviral resistance.