Plasma exosomes can deliver exogenous short interfering RNA to monocytes and lymphocytes

被引：643

作者：

Wahlgren, Jessica ^{[1
]}

Karlson, Tanya De L. ^{[1
]}

Brisslert, Mikael ^{[1
]}

Sani, Forugh Vaziri ^{[1
]}

Telemo, Esbjorn ^{[1
]}

Sunnerhagen, Per ^{[2
]}

Valadi, Hadi ^{[1
]}

机构：

[1] Univ Gothenburg, Sahlgrenska Acad, Dept Rheumatol & Inflammat Res, S-40530 Gothenburg, Sweden

[2] Univ Gothenburg, Lundberg Lab, Dept Chem & Mol Biol, S-40530 Gothenburg, Sweden

来源：

NUCLEIC ACIDS RESEARCH | 2012年 / 40卷 / 17期

基金：

瑞典研究理事会;

关键词：

HUMAN SALIVA; T-CELLS; BIOMARKERS; ACTIVATION; VESICLES;

D O I：

10.1093/nar/gks463

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Despite the promise of RNA interference (RNAi) and its potential, e.g. for use in cancer therapy, several technical obstacles must first be overcome. The major hurdle of RNAi-based therapeutics is to deliver nucleic acids across the cell's plasma membrane. This study demonstrates that exosome vesicles derived from humans can deliver short interfering RNA (siRNA) to human mononuclear blood cells. Exosomes are nano-sized vesicles of endocytic origin that are involved in cell-to-cell communication, i.e. antigen presentation, tolerance development and shuttle RNA (mainly mRNA and microRNA). Having tested different strategies, an optimized method (electroporation) was used to introduce siRNA into human exosomes of various origins. Plasma exosomes (exosomes from peripheral blood) were used as gene delivery vector (GDV) to transport exogenous siRNA to human blood cells. The vesicles effectively delivered the administered siRNA into monocytes and lymphocytes, causing selective gene silencing of mitogen-activated protein kinase 1. These data suggest that human exosomes can be used as a GDV to provide cells with heterologous nucleic acids such as therapeutic siRNAs.

引用

页数：12

共 33 条

[1]

Exosomes with major histocompatibility complex class II and co-stimulatory molecules are present in human BAL fluid [J].