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Infection of intact human islets by a lentiviral vector

Gene Therapy volume 6, pages 1545–1551 (1999)Cite this article

Abstract

The transfer of genes encoding immunomodulatory proteins to islets can be used to improve islet function, block apoptosis, and inhibit rejection following transplantation. Adenoviral vectors have been shown to infect intact human islets, but the immunogenicity and transient gene expression of the current adenoviral vectors may hinder their use clinically for islet transplantation. In this report, we compared an HIV-1-based lentiviral vector with the E1-deleted adenoviral vehicle of the Ad5 type for gene transfer to human islets in vitro. We demonstrate that at similar viral particle concentrations per islet that an HIV-based lentiviral vector is able to infect β-cells within an intact human islet at an efficiency similar to an adenoviral vector. In addition, both the adenoviral and lentiviral vectors were able to express significant levels of soluble interleukin-1 receptor antagonist (IL-1Ra) protein following infection of intact islets. More importantly, there was no impairment of islet β-cell function following adenoviral and lentiviral infection in responding to glucose stimulation. These results support the utility of replication-defective lentiviral vectors as efficient gene delivery vehicles to islets to faciliate transplantation of islets for therapy of type I diabetes.

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Acknowledgements

We thank Elina Linetsky and Alessandra Ranuncoli from the Diabetes Research Institute of the University of Florida School of Medicine for human islet isolation. We also thank Joanna Stanson for the FACS analysis. NG is a recipient of a post-doctoral fellowship from the Juvenile Diabetes Foundation International and the Fonds pour la Formation de Chercheurs et à l’Aide à la Recherche prize (Fonds FCAR) of the provincial government of Quebec, Canada. This work was supported in part by Public Health Service Award DK44395 from the National Institutes of Health.

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Authors and Affiliations

  1. Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    N Giannoukakis, Z Mi, A Gambotto & P D Robbins

  2. Diabetes Research Institute, University of Miami, Miami, FL, USA

    C Ricordi

  3. Division of Immunogenetics, Department of Pediatrics, Children’s Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    A Eramo & M Trucco

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  1. N Giannoukakis
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  2. Z Mi
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Giannoukakis, N., Mi, Z., Gambotto, A. et al. Infection of intact human islets by a lentiviral vector. Gene Ther 6, 1545–1551 (1999). https://doi.org/10.1038/sj.gt.3300996

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