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Characterization of a third generation lentiviral vector pseudotyped with Nipah virus envelope proteins for endothelial cell transduction

Gene Therapy volume 20, pages 997–1005 (2013)Cite this article

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Abstract

Lentiviruses are becoming progressively more popular as gene therapy vectors due to their ability to integrate into quiescent cells and recent clinical trial successes. Directing these vectors to specific cell types and limiting off-target transduction in vivo remains a challenge. Replacing the viral envelope proteins responsible for cellular binding, or pseudotyping, remains a common method to improve lentiviral targeting. Here, we describe the development of a high titer, third generation lentiviral vector pseudotyped with Nipah virus fusion protein (NiV-F) and attachment protein (NiV-G). Critical to high titers was truncation of the cytoplasmic domains of both NiV-F and NiV-G. As known targets of wild-type Nipah virus, primary endothelial cells are shown to be effectively transduced by the Nipah pseudotype. In contrast, human CD34+ hematopoietic progenitors were not significantly transduced. Additionally, the Nipah pseudotype has increased stability in human serum compared with vesicular stomatitis virus pseudotyped lentivirus. These findings suggest that the use of Nipah virus envelope proteins in third generation lentiviral vectors would be a valuable tool for gene delivery targeted to endothelial cells.

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Acknowledgements

We thank Dr Paul Rota (Center for Disease Control, Atlanta, GA) for plasmids containing the complementary DNA for NiV-G and NiV-F and Dr Christopher Broder (Uniformed Services University, Bethesda, MD) for the NiV-G and NiV-F antibodies. We also thank the National Gene Vector Biorepository (Indianapolis, IN) for the lentiviral production plasmids. HUVECs were a kind gift from the laboratory of Dr Merv Yoder (Indianapolis, IN). This work was supported by the National Institutes of Health grant P30HL101337-02.

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  1. Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA

    S R Witting, P Vallanda & A L Gamble

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Witting, S., Vallanda, P. & Gamble, A. Characterization of a third generation lentiviral vector pseudotyped with Nipah virus envelope proteins for endothelial cell transduction. Gene Ther 20, 997–1005 (2013). https://doi.org/10.1038/gt.2013.23

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