ADVANCES IN SYSTEMIC siRNA DELIVERY

Sequence-specific gene silencing with small interfering RNA (SiRNA) has transformed basic science research, and the efficacy of siRNA therapeutics in a variety of diseases is now being evaluated in preclinical and clinical trials. Despite its potential value, the highly negatively charged siRNA has the classic delivery problem of requiring transport across cell membranes to the cytosol. Consequently, carrier development for siRNA delivery is one of the most important problems to solve before siRNA con achieve widespread clinical use. An assortment of nonviral carriers, including liposomes, peptides, polymers and aptamers, ore being evaluated for their ability to shepherd siRNA to the target tissue and cross the plasma membrane barrier into the cell. Several promising carriers with low toxicity and increased specificity for disease targets have emerged for siRNA-based therapeutics. This review will discuss nonviral approaches for siRNA therapeutics, with particular focus on synthetic carriers for in vivo systemic delivery of siRNA.