ENDOSOMOLYTIC ACTIVITY OF CATIONIC LIPOSOMES ENHANCES THE DELIVERY OFHUMAN IMMUNODEFICIENCY VIRUS-1 TRANSACTIVATOR PROTEIN (TAT) TO MAMMALIAN-CELLS

We have explored the use of cationic liposomes to deliver the human im munodeficiency virus-1 trans-activator protein tat using a reporter ge ne expression assay. The human epidermoid carcinoma cell A431 stably t ransfected with a reporter gene under the control of human immunodefic iency virus-1 promoter was used as a target cell. Phosphatidylcholine- containing cationic liposomes had no detectable tat delivery activity. In contrast, delivery of tat was enhanced by up to 150-fold using cat ionic liposomes enriched with dioleoyl phosphatidylethanolamine (DOPE) , a lipid which readily transforms a bilayer into a nonbilayer structu re. Enhanced delivery of tat by DOPE-containing liposomes was most lik ely the result of the endosomolytic activity of the liposome. This pho spholipid-rich formulation showed no toxicity at concentrations suffic ient for maximal delivery of tat. A variety of cationic liposome formu lations which contain DOPE were tested successfully for rat delivery. (C) 1995 Academic Press, Inc.