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In vivo delivery of siRNA to immune cells by conjugation to a TLR9 agonist enhances antitumor immune responses.

Abstract：

:Efficient delivery of small interfering (si)RNA to specific cell populations in vivo remains a formidable challenge to its successful therapeutic application. We show that siRNA synthetically linked to a CpG oligonucleotide agonist of toll-like receptor (TLR)9 targets and silences genes in TLR9(+) myeloid cells and B cells, both of which are key components of the tumor microenvironment. When a CpG-conjugated siRNA that targets the immune suppressor gene Stat3 is injected in mice either locally at the tumor site or intravenously, it enters tumor-associated dendritic cells, macrophages and B cells. Silencing of Stat3 leads to activation of tumor-associated immune cells and ultimately to potent antitumor immune responses. Our findings demonstrate the potential of TLR agonist-siRNA conjugates for targeted gene silencing coupled with TLR stimulation and immune activation in the tumor microenvironment.

journal_name

Nat Biotechnol

journal_title

Nature biotechnology

authors

Kortylewski M,Swiderski P,Herrmann A,Wang L,Kowolik C,Kujawski M,Lee H,Scuto A,Liu Y,Yang C,Deng J,Soifer HS,Raubitschek A,Forman S,Rossi JJ,Pardoll DM,Jove R,Yu H

doi

10.1038/nbt.1564

subject

Has Abstract

pub_date

2009-10-01 00:00:00

pages

925-32

issue

10

eissn

1087-0156

issn

1546-1696

pii

nbt.1564

journal_volume

27

pub_type

杂志文章

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