PROTEOGLYCANS MEDIATE CATIONIC LIPOSOME-DNA COMPLEX-BASED GENE DELIVERY IN-VITRO AND IN-VIVO

The factors controlling cationic liposome-DNA complex (CLDC)-based gen e transfer in cells and in animals are poorly understood. me found tha t cell surface heparin/heparan sulfate-bearing proteoglycans mediate C LDC-based gene transfer and expression both in cultured cells and foll owing intravenous gene delivery into animals. CLDC did not transfect R aji cells, which lack proteoglycans, but did efficiently transfect Raj i cells stably transfected with the proteoglycan, syndecan-1, Fucoidan , heparin, or dextran sulfate, all of which are highly anionic polysac charides, each blocked CLDC-mediated transfection both in cultured cel ls and following intravenous injection into mice, but had no effect on transfection by either recombinant adenovirus infection or electropor ation. Intravenous pretreatment of mice with heparinases, which specif ically cleave heparan sulfate molecules from cell surface proteoglycan s, 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 an imals.