Transduction of Human Islets with Pseudotyped Lentiviral Vectors

Gary P. Kobinger, Shaoping Deng, Jean Pierre Louboutin, Marko Vatamaniuk, Franz Matschinsky, James F. Markmann, Steven E. Raper, James M. Wilson

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Type I diabetes is caused by an autoimmune-mediated elimination of insulin-secreting pancreatic islets. Genetic modification of islets offers a powerful molecular tool for improving our understanding of islet biology. Moreover, efficient genetic engineering of islets could allow for evaluation of new strategies aimed at preventing islet destruction. The present study evaluated the ability of a human immunodeficiency virus (HIV)-based lentiviral vector pseudotyped with various viral envelopes to target human islets ex vivo, with the goal of improving efficiency while minimizing toxicity. Transfer of the enhanced green fluorescent protein reporter gene in human islets was first evaluated with an HIV-based vector pseudotyped with the vesicular stomatitis virus (VSV), murine leukemia virus, Ebola, rabies, Mokola, or lymphocytic choriomeningitis virus (LCMV) envelope glycoprotein to optimize transduction efficiency. Results indicated that LCMV-pseudotyped vector transduced insulin-secreting beta cells with the highest efficiency. Moreover, toxicity associated with transduction of islets was found to be lower with LCMV-pseudotyped vector than with VSV-G-pseudotyped vector, the second most efficient vector for islet transduction. Overall, our study describes an improved methodology for achieving safe and efficient gene transfer into cells of human islets.

Original languageEnglish (US)
Pages (from-to)211-219
Number of pages9
JournalHuman Gene Therapy
Volume15
Issue number2
DOIs
StatePublished - Feb 2004
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

Fingerprint

Dive into the research topics of 'Transduction of Human Islets with Pseudotyped Lentiviral Vectors'. Together they form a unique fingerprint.

Cite this