Functional RNA Delivery Targeted to Dendritic Cells By Synthetic Nanoparticles

Abstract

Dendritic cells (DCs) are essential to many aspects of immune defense development and regulation. They provide important targets for prophylactic and therapeutic delivery. While protein delivery has had considerable success, RNA delivery is still expanding. Delivering RNA molecules for RNAi has shown particular success and there are reports on successful delivery of mRNA. Central, therein, is the application of cationic entities. Following endocytosis of the delivery vehicle for the RNA, cationic entities should promote vesicular membrane perturbation, facilitating cytosolic release. The present review explains the diversity of DC function in immune response development and control. Promotion of delivered RNA cytosolic release is discussed, relating to immunoprophylactic and therapeutic potential, and DC endocytic machinery is reviewed, showing how DC endocytic pathways influence the handling of internalized material. The potential advantages for application of replicating RNA are presented and discussed, in consideration of their value and development in the near future.

Financial & competing interests disclosure

The preparation of this article and the work of the authors mentioned therein was supported financially by the Institute of Virology and Immunoprophylaxis, and the grants PANFLUVAC (EU FP6 project 044115), Replixcel (EU FP7, Marie-Curie Industry-Academia Partnerships and Pathways project 251420), HCVAX (EU FP7 ERA-NET Euronanomed and Swiss National Science Foundation project 31NM30–136034) and NANOVACC (Swiss National Science Foundation project 310000–1198828). KC McCullough and N Ruggli are associated with the replicon technology for the swine fever virus replicon covered by patent numbers WO2009/146867, EP2130912 and WO2010/067318. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.