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Blood, 19 March 2009, Vol. 113, No. 12, pp. 2646-2654. Prepublished online as a Blood First Edition Paper on January 22, 2009; DOI 10.1182/blood-2008-04-151191. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2008-04-151191v1 113/12/2646    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Zheng, X. Articles by Min, W.-P. Search for Related Content PubMed PubMed Citation Articles by Zheng, X. Articles by Min, W.-P. Related Collections Immunobiology Gene Therapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  GENE THERAPY A novel in vivo siRNA delivery system specifically targeting dendritic cells and silencing CD40 genes for immunomodulation Xiufen Zheng1,2,*, Costin Vladau1,*, Xusheng Zhang1,2, Motohiko Suzuki1, Thomas E. Ichim3, Zhu-Xu Zhang1,2, Mu Li1, Ewa Carrier4, Bertha Garcia1, Anthony M. Jevnikar1,2,5, and Wei-Ping Min1,2,5 1 Departments of Surgery, Pathology, Microbiology and Immunology, and Medicine, University of Western Ontario, London, ON; 2 Multi-Organ Transplant Program, London Health Sciences Centre, London, ON; 3 Medistem Laboratories, San Diego, CA; 4 Moores UCSD Cancer Center and Department of Medicine, University of California–San Diego, La Jolla; and 5 Transplantation and Regenerative Medicine, Lawson Health Research Institute, London, ON Translation of small interfering RNA (siRNA)–based approaches into practical therapeutics is limited because of 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. On 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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