Small RNAs: The Qualified Candidates for Gene Manipulation in Diverse Clinical Pathologies

In recent years, RNA interference (RNAi) has become a tool of choice to analyze and target the in vitro and in vivo function of mammalian genes. RNAi down-regulates gene expression by inducing enzyme-dependent degradation of targeted mRNA. This can be achieved using small double-stranded RNAs (dsRNAs), including small interfering RNAs (siRNAs), micro RNAs, and piwi RNAs. These active, small dsRNAs can regulate endogenous genes in both somatic and germ cells such that they can defend the genome from invasive nucleic acids. Extension of the concept of RNAi to preclinical studies indicates its probable application in the treatment of cancers, viral infections, arterial stenosis, and genetic disorders. Exciting results from ongoing clinical trials have raised the expectations of the scientific community for the use of RNAi in real cures. Rational pharmaceutical design of these molecules can further open a Pandora's box of newer therapeutic options. However, efficient delivery of these small dsRNAs to target tissues or cells and their unanticipated nonspecific effects comprise a few important issues that still need to be addressed. In this review, we offer an overview of different small dsRNAs, their biogenesis, and their applicability in therapeutics. Current delivery strategies and formulation techniques to achieve the desired transfection capability and RNAi products in clinical trials are also discussed.