Advances in siRNA delivery to T-cells: potential clinical applications for inflammatory disease, cancer and infection.
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.
*Department of Clinical Medicine, Institute of Molecular Medicine, Trinity College Dublin, Dublin, Ireland.
Michael
M
Freeley
Aideen
A
Long
D000818:Animals; D020868:Gene Silencing; D018390:Gene Targeting; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007239:Infections / Q000628:therapy; D007249:Inflammation / Q000235:genetics / Q000628:therapy*; D051379:Mice; D023421:Models, Animal; D009369:Neoplasms / Q000235:genetics / Q000628:therapy*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000737:chemistry / Q000235:genetics*; D013601:T-Lymphocytes
D034741:RNA, Small Interfering