Strategies for short hairpin RNA delivery in cancer gene therapy

RNA interference (RNAi) gene silencing can be achieved by delivering vectors that transcribe short hairpin RNA (shRNA), which stably express small interfering RNA in target cells. Therefore, shRNA is of potential therapeutic use for inhibiting cancer cells, in which aberrant expression of certain mRNA's causes problems. However, this technique has not yet been developed for cancer therapy. The major problem for clinical use is lack of effective methods of delivery. In this article, we review the current strategies for shRNA delivery for target validation and their therapeutic uses in cancer to help further the understanding of challenges confronting shRNA technology, such as different principles of RNAi technology, basic construction of shRNA-expressing vectors and delivery barriers, which exist for both local and systemic delivery stratiges. Even if there are data showing that shRNA can be used in mice, we are still a long way from its application in human cancer therapy, because serious problems remain, including biodistribution and clearance of nanoparticles following systemic delivery of shRNA-expressing vectors.