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.

journal_name

Blood

journal_title

Blood

authors

Zheng X,Vladau C,Zhang X,Suzuki M,Ichim TE,Zhang ZX,Li M,Carrier E,Garcia B,Jevnikar AM,Min WP

doi

10.1182/blood-2008-04-151191

subject

Has Abstract

pub_date

2009-03-19 00:00:00

pages

2646-54

issue

12

eissn

0006-4971

issn

1528-0020

pii

blood-2008-04-151191

journal_volume

113

pub_type

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