Transduction of human and mouse pancreatic islet cells using a bicistronic recombinant adeno-associated viral vector

Matthias Kapturczak, Sergei Zolotukhin, Jeff Cross, Antonello Pileggi, R. Damaris Molano, Marda Jorgensen, Barry Byrne, Terence R. Flotte, Tamir Ellis, Luca Inverardi, Camillo Ricordi, Harry Nick, Mark Atkinson, Anupam Agarwal

Research output: Contribution to journalArticlepeer-review

30 Scopus citations


Recent reports indicate successful transduction of pancreatic islets using recombinant adeno-associated viral (rAAV) vectors. This advance offers new possibilities in rendering islets resistant to rejection and recurrence of autoimmune destruction in the setting of islet transplantation as treatment of type 1 diabetes. Most gene delivery approaches using islets have thus far involved transduction with a single gene. However, the concomitant delivery of more than one gene encoding cytoprotective and/or immunoregulatory molecules may offer superior clinical utility. Here, we have generated a bicistronic rAAV (serotype 2) vector incorporating a viral internal ribosome entry site (IRES), derived from polio virus type 1, to allow for translation of two coupled cDNAs from a single mRNA transcript. Our study demonstrates the ability of this vector to produce significant expression of two reporter proteins in human and mouse islets in vitro. This expression did not interfere with β-cell function. Transduction was maintained in vivo following transplantation of mouse islets. These data are the first report of efficient islet cell transduction with two genes using a single bicistronic rAAV vector and have direct implications for strategies aimed at enhancing islet transplant survival.

Original languageEnglish (US)
Pages (from-to)154-160
Number of pages7
JournalMolecular Therapy
Issue number2
StatePublished - 2002


  • Adeno-associated virus
  • Autoimmunity
  • Bicistronic vector
  • Diabetes
  • Gene therapy
  • Islet transplantation
  • Transplant rejection

ASJC Scopus subject areas

  • Molecular Biology


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