Engineering ‘smart’ viral RNA structures for stable and targeted siRNA delivery

Innovative delivery strategies are needed in order to realize the potential of small interfering RNA (siRNA) in medicine. SiRNAs are short, double-stranded RNA molecules that silence genes by co-opting an endogenous RNA interference (RNAi) pathway. Because they act on messenger RNA (mRNA) sequences via RNAi, siRNAs hold promise as potentially curative therapies for genetic defects, autoimmune disorders, cancers, and other diseases that cannot be treated with traditional, protein-binding small molecule drugs and biologics. However, key physiological barriers largely have precluded the translation of siRNA drugs into clinical practice. In vivo, naked siRNAs are degraded rapidly by nucleases and cleared by the kidneys, resulting in a half-life of less than five minutes. Moreover, by comparison to small molecule drugs, siRNA drugs are relatively large, hydrophilic molecules that do not distribute widely to tissues or passively cross the cell membrane. Therefore, without an effective strateg...