Systemic siRNA delivery to leukocyte-implicated diseases.
Short interfering RNA (siRNA), a small duplex of RNA fragment, has proved as an extremely useful research tool to interrogate gene functions in test tubes. However, the transformation of siRNAs from a functional genomic tool into a new therapeutic modality has been hindered by ineffective delivery methods for systemic administration. In this review, we will discuss the recent advances in formulating new delivery strategies that target siRNAs to specific cells following systemic administration. Special emphasis will be given to leukocytes, since siRNA delivery remains exceptionally challenging here due to the unavailability of effective delivery technologies. We will not only detail new platforms that utilize leukocyte integrins as receptor targets for siRNAs delivery, but also show how one of these strategies has been utilized for in vivo drug target validation of a novel anti-inflammatory target, cyclin D1, for inflammatory bowel diseases.
Peer
Dan
D
Department of Cell Research and Immunology, Laboratory for Nanomedicine, George S Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel. peer@post.tau.ac.il
Shimaoka
Motomu
M
D000818:Animals; D002986:Clinical Trials as Topic; D019938:Cyclin D1 / Q000378:metabolism*; D016503:Drug Delivery Systems; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000628:therapy*; D007962:Leukocytes / Q000378:metabolism*; D053758:Nanoparticles / Q000008:administration & dosage*; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics
D034741:RNA, Small Interfering; D019938:Cyclin D1