Vector Systems for the Delivery of Small Interfering RNAs: Managing the RISC

Silence is golden: Recent breakthroughs in the field of RNA interference have made it feasible to engineer DNA vectors capable of selectively silencing the expression of genes in a wide variety of cell types. For example, lentiviral vectors containing an RNA polymerase III promoter such as U6 have been developed for the expression of small RNA hairpins. These RNA hairpin transcripts serve as substrates for the cytoplasmic ribonuclease Dicer, generating small interfering RNAs (siRNAs) capable of inducing RNA interference in association with the RNA-induced silencing complex (RISC). A variety of vector strategies have been employed to achieve siRNA expression and long-term gene suppression. Recent studies have provided new insights into how these vector strategies might be refined to achieve potent and specific gene suppression, while minimizing the risks associated with these approaches.