Submitted April 15, 2008
Accepted December 24, 2008
A novel in vivo siRNA delivery system specifically targeting dendritic cells and silencing CD40 genes for immunomodulation
Xiufen Zheng, Costin Vladau, Xusheng Zhang, Motohiko Suzuki, Thomas E Ichim, Zhu-Xu Zhang, Mu Li, Ewa Carrier, Bertha Garcia, Anthony M Jevnikar, and Wei-Ping Min*
Department of Surgery, Pathology, Microbiology and Immunology, Medicine, University of Western Ontario, London, Ontario, Canada
Multi-Organ Transplant Program, London Health Sciences Centre, London, Ontario, Canada
Medistem Laboratories, San Diego, CA, United States
Moores UCSD Cancer Center and Department of Medicine UCSD, La Jolla, CA, United States
Transplantation and Regenerative Medicine, Lawson Health Research Institute, London, Ontario, Canada
* Corresponding author; email: weiping.min{at}uwo.ca.
Translation of siRNA-based approaches into practical therapeutics is limited due to lack of an effective and cell-specific delivery system. Herein, we present a new method of selectively delivering siRNA to dendritic cells (DCs) in vivo using CD40 siRNA-containing immunoliposomes (siILs) that were decorated with DC-specific DEC-205 mAb. Administration of CD40 siILs resulted in DC-specific cell targeting in vitro and in vivo. Upon treatment with CD40 siILs, the expression of CD40 in DCs, as well allostimulatory activity was inhibited. In vivo administration resulted in selective siRNA uptake into immune organs and functional immune modulation as assessed using a model antigen. In conclusion, this is the first demonstration of DC-specific siRNA delivery and gene silencing in vivo, which highlights the potential of DC-mediated immune modulation and the feasibility of siRNA-based clinical therapy.
