rna Interference and micro-rna–Oriented Therapy in Cancer: Rationales, Promises, and Challenges

The discovery that rna interference (rnai) and its functional derivatives, small interfering rnas (sirnas) and micro-rnas (mirnas) could mediate potent and specific gene silencing has raised high hopes for cancer therapeutics. The prevalence of these small (18–25 nucleotide) non-coding rnas in human gene networks, coupled with their unique specificity, has paved the way for the development of new and promising therapeutic strategies in re-directing or inhibiting small rna phenomena. Three strategies are currently being developed: (1) De novo rnai programming using synthetic sirnas to target the expression of genes; (2) Strengthening or recapitulation of the physiologic targeting of messenger rnas by specific mirnas; (3) Sequence-specific inhibition of mirna functions by nucleic acid analogs. Each strategy, currently being developed both in academia and in industry, holds promise in cancer therapeutics.