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Infection of intact human islets by a lentiviral vector

Academic Article
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Overview

authors

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

publication date

  • September 1999

journal

  • Gene Therapy  Journal

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 beta-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 beta-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.

subject areas

  • Adenoviridae
  • Apoptosis
  • Cells, Cultured
  • Defective Viruses
  • Flow Cytometry
  • Gene Expression
  • Gene Transfer Techniques
  • Genetic Vectors
  • Glucose
  • Green Fluorescent Proteins
  • HIV-1
  • Humans
  • In Vitro Techniques
  • Insulin
  • Interleukin 1 Receptor Antagonist Protein
  • Islets of Langerhans
  • Luminescent Proteins
  • Recombinant Proteins
  • Sialoglycoproteins
  • beta-Galactosidase
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Research

keywords

  • adenovirus
  • diabetes
  • islets
  • lentivirus
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Identity

International Standard Serial Number (ISSN)

  • 0969-7128

Digital Object Identifier (DOI)

  • 10.1038/sj.gt.3300996

PubMed ID

  • 10490763
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Additional Document Info

start page

  • 1545

end page

  • 1551

volume

  • 6

issue

  • 9

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