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J Virol, June 1998, p. 4832-4840, Vol. 72, No. 6
Chester Beatty Laboratories,
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.
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
*
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.
Present address: Department of Immunology, Windeyer Institute of
Medical Science, London W1P 6DB, United Kingdom.
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