First Author | Freeley M | Year | 2013 |
Journal | Biochem J | Volume | 455 |
Issue | 2 | Pages | 133-47 |
PubMed ID | 24070422 | Mgi Jnum | J:205000 |
Mgi Id | MGI:5543859 | Doi | 10.1042/BJ20130950 |
Citation | Freeley M, et al. (2013) Advances in siRNA delivery to T-cells: potential clinical applications for inflammatory disease, cancer and infection. Biochem J 455(2):133-47 |
abstractText | The specificity of RNAi and its ability to silence 'undruggable' targets has made inhibition of gene expression in T-cells with siRNAs an attractive potential therapeutic strategy for the treatment of inflammatory disease, cancer and infection. However, delivery of siRNAs into primary T-cells represents a major hurdle to their use as potential therapeutic agents. Recent advances in siRNA delivery through the use of electroporation/nucleofection, viral vectors, peptides/proteins, nanoparticles, aptamers and other agents have now enabled efficient gene silencing in primary T-cells both in vitro and in vivo. Overcoming such barriers in siRNA delivery offers exciting new prospects for directly targeting T-cells systemically with siRNAs, or adoptively transferring T-cells back into patients following ex vivo manipulation with siRNAs. In the present review, we outline the challenges in delivering siRNAs into primary T-cells and discuss the mechanism and therapeutic opportunities of each delivery method. We emphasize studies that have exploited RNAi-mediated gene silencing in T-cells for the treatment of inflammatory disease, cancer and infection using mouse models. We also discuss the potential therapeutic benefits of manipulating T-cells using siRNAs for the treatment of human diseases. |