title: A novel in vivo siRNA delivery system specifically targeting dendritic cells and silencing CD40 genes for immunomodulation.
abstract: 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.
authors.affiliation: Department of Surgery, University of Western Ontario, London, ON, Canada.
authors.forename: Xiufen
authors.initials: X
authors.lastname: Zheng
authors.forename: Costin
authors.initials: C
authors.lastname: Vladau
authors.forename: Xusheng
authors.initials: X
authors.lastname: Zhang
authors.forename: Motohiko
authors.initials: M
authors.lastname: Suzuki
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Ichim
authors.forename: Zhu-Xu
authors.initials: ZX
authors.lastname: Zhang
authors.forename: Mu
authors.initials: M
authors.lastname: Li
authors.forename: Ewa
authors.initials: E
authors.lastname: Carrier
authors.forename: Bertha
authors.initials: B
authors.lastname: Garcia
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Jevnikar
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Min
mesh_terms: 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
chemical_list: 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