A novel in vivo siRNA delivery system specifically targeting dendritic cells and silencing CD40 genes for immunomodulation

被引：82

作者：

Zheng, Xiufen ^{[1
,2
,3
,4
,5
]}

Vladau, Costin ^{[1
,2
,3
,4
]}

Zhang, Xusheng ^{[1
,2
,3
,4
,5
]}

Suzuki, Motohiko ^{[1
,2
,3
,4
]}

Ichim, Thomas E. ^{[6
]}

Zhang, Zhu-Xu ^{[1
,2
,3
,4
,5
]}

Li, Mu ^{[1
,2
,3
,4
]}

Carrier, Ewa ^{[7
,8
]}

Garcia, Bertha ^{[1
,2
,3
,4
]}

Jevnikar, Anthony M. ^{[1
,2
,3
,4
,5
,9
]}

Min, Wei-Ping ^{[1
,2
,3
,4
,5
,9
]}

机构：

[1] Univ Western Ontario, Dept Surg, London, ON N6A 3K7, Canada

[2] Univ Western Ontario, Dept Pathol, London, ON N6A 3K7, Canada

[3] Univ Western Ontario, Dept Microbiol & Immunol, London, ON N6A 3K7, Canada

[4] Univ Western Ontario, Dept Med, London, ON N6A 3K7, Canada

[5] London Hlth Sci Ctr, Multiorgan Transplant Program, London, ON, Canada

[6] Medistem Labs, San Diego, CA USA

[7] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA

[8] Univ Calif San Diego, Moores UCSD Canc Ctr, La Jolla, CA 92093 USA

[9] Lawson Hlth Res Inst, London, ON, Canada

来源：

BLOOD | 2009年 / 113卷 / 12期

关键词：

RNA INTERFERENCE; ANTIGEN PRESENTATION; IMMUNE MODULATION; EXPRESSION; INDUCTION; TOLERANCE; THERAPY; MOUSE; DNA; LIPOSOMES;

D O I：

10.1182/blood-2008-04-151191

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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. (Blood. 2009;113:2646-2654)

引用

页码：2646 / 2654

页数：9

共 43 条

[21] Dendritic cells genetically engineered to express Fas ligand induce donor-specific hyporesponsiveness and prolong allograft survival [J].