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J Virol, June 1998, p. 4832-4840, Vol. 72, No. 6
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Cationic Liposomes Enhance the Rate of Transduction by a Recombinant Retroviral Vector In Vitro and In Vivo

Colin D. Porter,1,* Katalin V. Lukacs,1,2 Gary Box,1 Yasuhiro Takeuchi,1 and Mary K. L. Collins1,dagger

Chester Beatty Laboratories, Institute of Cancer Research, London SW3 6JB,1 and National Heart and Lung Institute, Imperial College, London SW3 6LR,2 United Kingdom

Received 15 October 1997/Accepted 20 February 1998

Cationic liposomes enhanced the rate of transduction of target cells with retroviral vectors. The greatest effect was seen with the formulation DC-Chol/DOPE, which gave a 20-fold increase in initial transduction rate. This allowed an efficiency of transduction after brief exposure of target cells to virus plus liposome that could be achieved only after 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 concentration. Cationic liposomes, but not Polybrene, were able to mediate envelope-independent transduction, but optimal efficiency required envelope-receptor interaction. When virus complexed with DC-Chol/DOPE was used to transduce human mesothelioma xenografts, transduction was enhanced four- to fivefold compared to that for virus alone. Since the efficacy of gene therapy is dependent on the number of cells modified, which is in turn dependent upon the balance between transduction and biological 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.


* Corresponding author. Mailing address: Chester Beatty Laboratories, Institute of Cancer Research, 237 Fulham Rd., London SW3 6JB, United Kingdom. Phone: 171 352 8133. Fax: 171 352 3299. E-mail: c.porter{at}icr.ac.uk.

dagger Present address: Department of Immunology, Windeyer Institute of Medical Science, London W1P 6DB, United Kingdom.


J Virol, June 1998, p. 4832-4840, Vol. 72, No. 6
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.



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