Infection of intact human islets by a lentiviral vector

N. Giannoukakis, Z. Mi, A. Gambotto, A. Eramo, C. Ricordi, M. Trucco, P. D. Robbins

Research output: Contribution to journalArticle

55 Scopus citations

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 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.

Original languageEnglish (US)
Pages (from-to)1545-1551
Number of pages7
JournalGene Therapy
Volume6
Issue number9
DOIs
StatePublished - Sep 1 1999

Keywords

  • Adenovirus
  • Diabetes
  • Islets
  • Lentivirus

ASJC Scopus subject areas

  • Genetics

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    Giannoukakis, N., Mi, Z., Gambotto, A., Eramo, A., Ricordi, C., Trucco, M., & Robbins, P. D. (1999). Infection of intact human islets by a lentiviral vector. Gene Therapy, 6(9), 1545-1551. https://doi.org/10.1038/sj.gt.3300996