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Technical Report
Nature Medicine  11, 346 - 352 (2005)
Published online: 13 February 2005; | doi:10.1038/nm1192

Lentiviral vector retargeting to P-glycoprotein on metastatic melanoma through intravenous injection

Kouki Morizono1, 2, Yiming Xie1, 2, Gene-Errol Ringpis1, 2, Mai Johnson3, Hoorig Nassanian1, Benhur Lee1, 4, Lily Wu3 & Irvin S Y Chen1, 2, 5

1  Department of Microbiology, Immunology and Molecular Genetics, University of California, 10833 Le Conte Avenue, Los Angeles, California 90095, USA.

2  UCLA AIDS Institute, University of California, 10833 Le Conte Avenue, Los Angeles, California 90095, USA.

3  Department of Urology, University of California, 10833 Le Conte Avenue, Los Angeles, California 90095, USA.

4  Department of Pathology and Laboratory Medicine, University of California, 10833 Le Conte Avenue, Los Angeles, California 90095, USA.

5  Department of Medicine, David Geffen School of Medicine, University of California, 10833 Le Conte Avenue, Los Angeles, California 90095, USA.

Correspondence should be addressed to Irvin S Y Chen syuchen@mednet.ucla.edu
Targeted gene transduction to specific tissues and organs through intravenous injection would be the ultimate preferred method of gene delivery. Here, we report successful targeting in a living animal through intravenous injection of a lentiviral vector pseudotyped with a modified chimeric Sindbis virus envelope (termed m168). m168 pseudotypes have high titer and high targeting specificity and, unlike other retroviral pseudotypes, have low nonspecific infectivity in liver and spleen. A mouse cancer model of metastatic melanoma was used to test intravenous targeting with m168. Human P-glycoprotein was ectopically expressed on the surface of melanoma cells and targeted by the m168 pseudotyped lentiviral vector conjugated with antibody specific for P-glycoprotein. m168 pseudotypes successfully targeted metastatic melanoma cells growing in the lung after systemic administration by tail vein injection. Further development of this targeting technology should result in applications not only for cancers but also for genetic, infectious and immune diseases.

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Nature Medicine
ISSN: 1078-8956
EISSN: 1546-170X
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