A daunting task: manipulating leukocyte function with RNAi.

RNA interference (RNAi) has advanced into clinical trials. In spite of the progress made in systemic RNAi delivery to the liver and solid tumors, delivery of RNAi to leukocytes remains challenging and less advanced. Manipulating leukocyte function with RNAi holds great promise for streamlining the drug discovery process by facilitating in vivo drug target validation and for facilitating the development of RNAi-based therapy platforms for leukocyte-implicated diseases, such as blood cancer, inflammation, and leukocyte-tropic viral infections. In this review, progress in delivery strategies of RNAi payloads to leukocytes, which are notoriously difficult cells to transduce with RNAi, is discussed with special emphasis on the challenges and potential opportunities for manipulating leukocyte function with RNAi.