Proteoglycans Mediate Cationic Liposome-DNA Complex-based Gene Delivery in Vitro and in Vivo

作者：Leslie C. Mounkes, Wendy Zhong, Guadalupe Cipres-Palacin, Timothy D. Heath, Robert J. Debs · 发表于：Journal of Biological Chemistry · 年份：1998 · DOI：10.1074/jbc.273.40.26164 · 被引用次数：242 · 研究领域：RNA Interference and Gene Delivery、Virus-based gene therapy research、Viral Infectious Diseases and Gene Expression in Insects

The factors controlling cationic liposome-DNA complex (CLDC)-based gene transfer in cells and in animals are poorly understood. We found that cell surface heparin/heparan sulfate-bearing proteoglycans mediate CLDC-based gene transfer and expression both in cultured cells and following intravenous gene delivery into animals. CLDC did not transfect Raji cells, which lack proteoglycans, but did efficiently transfect Raji cells stably transfected with the proteoglycan, syndecan-1. Fucoidan, heparin, or dextran sulfate, all of which are highly anionic polysaccharides, each blocked CLDC-mediated transfection both in cultured cells and following intravenous injection into mice, but had no effect on transfection by either recombinant adenovirus infection or electroporation. Intravenous pretreatment of mice with heparinases, which specifically cleave heparan sulfate molecules from cell surface proteoglycans, blocked intravenous, CLDC-mediated transfection in mice, confirming that proteoglycans mediate CLDC gene delivery in vivo. Modulation of proteoglycan expression may prove useful in controlling the efficiency of, as well as targeting the sites of, CLDC-based gene transfer in animals.