Journal
BIOCHEMICAL JOURNAL
Volume 455, Issue -, Pages 133-147Publisher
PORTLAND PRESS LTD
DOI: 10.1042/BJ20130950
Keywords
gene silencing; knockdown; RNAi; siRNA; T-cell; therapeutic
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Funding
- Programme for Research in Third Level Institutions in Ireland (PRTLI)
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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.
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