Targeted delivery of siRNA by nonviral vectors: lessons learned from recent advances.

siRNA is a potential therapeutic candidate for treating genetic and acquired diseases, including cancer, that cannot be easily cured by conventional drugs. The limiting step for siRNA-based therapy is the delivery of the oligonucleotide into target cells by systemic administration. Several strategies, including chemical modification and nanoparticle formulation, have been developed to improve the delivery of siRNA into a variety of target tissues. In this review, significant advances in the field over the past year are highlighted and key findings and technologies are discussed. First, the elucidation of the liver-targeting mechanism of lipid-conjugated siRNA, which may lead to further optimization of conjugates, is presented. The development of different materials and formulations to overcome delivery barriers and enhance RNAi efficiency is also presented, in addition to strategies to manage siRNA immunotoxicity (eg, chemical modification). Finally, remaining challenges and future perspectives in the field are discussed.