Advances in the development of siRNA-based therapeutics for cancer

Short interfering (si)RNA represents a promising novel therapeutic modality for the treatment of cancer. However, delivering siRNA to tumors via clinically relevant means is a major technical hurdle that has impeded the successful development of siRNA-based cancer therapeutics. Significant progress has been made in recent years for the delivery of siRNA to tumors, and several promising siRNA delivery platforms have begun to emerge. These platforms include liposomes, in which siRNA is encapsulated in a lipid vesicle; polyplexes, in which a cationic carrier is used to bind siRNA to form siRNA-containing nanoparticles; liposome-polycation-DNA (LPD) complexes, in which an siRNA-containing polyplex is encapsulated in a lipid vesicle; and siRNA conjugates, in which siRNA is coupled to a targeting moiety that carries the siRNA into target cells via receptor-mediated endocytosis. An unbiased, independent evaluation of various tumor-delivery approaches will be a critical starting point in identifying the most promising delivery platforms for the development of siRNA-based cancer therapeutics.