A novel in vivo siRNA delivery system specifically targeting dendritic cells and silencing CD40 genes for immunomodulation.
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.
Zheng
Xiufen
X
Department of Surgery, University of Western Ontario, London, ON, Canada.
Vladau
Costin
C
Zhang
Xusheng
X
Suzuki
Motohiko
M
Ichim
Thomas E
TE
Zhang
Zhu-Xu
ZX
Li
Mu
M
Carrier
Ewa
E
Garcia
Bertha
B
Jevnikar
Anthony M
AM
Min
Wei-Ping
WP
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology; D017951:Antigen Presentation / Q000187:drug effects*; D015703:Antigens, CD / Q000276:immunology; D001854:Bone Marrow Cells / Q000166:cytology; D019013:CD40 Antigens / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured / Q000187:drug effects / Q000276:immunology; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D016503:Drug Delivery Systems; D015316:Genetic Therapy / Q000379:methods*; D018796:Immunoconjugates / Q000008:administration & dosage; D007165:Immunosuppression Therapy / Q000379:methods*; D037181:Lectins, C-Type / Q000276:immunology; D008081:Liposomes; D008213:Lymphocyte Activation / Q000187:drug effects; D008221:Lymphoid Tissue / Q000187:drug effects / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D015778:Minor Histocompatibility Antigens; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D011956:Receptors, Cell Surface / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D019013:CD40 Antigens; C093569:DEC-205 receptor; D018796:Immunoconjugates; D037181:Lectins, C-Type; D008081:Liposomes; D015778:Minor Histocompatibility Antigens; D034741:RNA, Small Interfering; D011956:Receptors, Cell Surface