CATIONIC LIPOSOMES ENHANCE THE RATE OF TRANSDUCTION BY A RECOMBINANT RETROVIRAL VECTOR IN-VITRO AND IN-VIVO

Cationic liposomes enhanced the rate of transduction of target cells w ith retroviral vectors. The greatest effect was seen with the formulat ion DC-Chol/DOPE, which gave a 20-fold increase in initial transductio n rate. This allowed an efficiency of transduction after brief exposur e of target cells to virus plus liposome that could be achieved only a fter extensive exposure to virus alone. Enhancement with DC-Chol/DOPE was optimal when stable virion-liposome complexes were preformed. The transduction rate for complexed virus, as for virus used alone or with the polycation Polybrene, showed first-order dependence on virus conc entration. Cationic liposomes, but not Polybrene, were able to mediate envelope-independent transduction? but optimal efficiency required en velope-receptor interaction. When virus complexed with DC-Chol/DOPE wa s used to transduce human mesothelioma xenografts, transduction was en hanced four-to fivefold compared to that for virus alone. Since the ef ficacy of gene therapy is dependent on the number of cells modified, w hich is in turn dependent upon the balance between transduction and bi ological clearance of the vector, the ability of cationic liposomes to form stable complexes with retroviral vectors and enhance their rate of infection is likely to be important for in vivo application.