Targeting recombinant adeno-associated virus vectors to enhance gene transfer to pancreatic islets and liver

S. A. Loiler, T. J. Conlon, S. Song, Q. Tang, K. H. Warrington, A. Agarwal, M. Kapturczak, C. Li, Camillo Ricordi, M. A. Atkinson, N. Muzyczka, T. R. Flotte

Research output: Contribution to journalArticle

86 Citations (Scopus)

Abstract

Human pancreatic islet cells and hepatocytes represent the two most likely target cells for genetic therapy of type I diabetes. However, limits to the efficiency of rAAV serotype 2 (rAAV2)-mediated gene transfer have been reported for both of these cell targets. Here we report that nonserotype 2 AAV capsids can mediate more efficient transduction of islet cells, with AAV1 being the most efficient serotype in murine islets, suggesting that receptor abundance could be limiting. In order to test this, we generated rAAV particles that display a ligand (ApoE) that targets the low-density lipoprotein receptor, which is present on both of these cell types. The rAAV/ApoE viruses greatly enhanced the efficiency of transduction of both islet cells ex vivo and murine hepatocytes in vivo when compared to native rAAV2 serotype (220- and four-fold, respectively). The use of receptor-targeted rAAV particles may circumvent the lower abundance of receptors on certain nonpermissive cell types.

Original languageEnglish
Pages (from-to)1551-1558
Number of pages8
JournalGene Therapy
Volume10
Issue number18
DOIs
StatePublished - Sep 1 2003

Fingerprint

Dependovirus
Islets of Langerhans
Liver
Apolipoproteins E
Genes
Hepatocytes
LDL Receptors
Capsid
Cell- and Tissue-Based Therapy
Type 1 Diabetes Mellitus
Genetic Therapy
Ligands
Viruses
Serogroup

Keywords

  • Adeno-associated virus
  • Diabetes
  • Targeting

ASJC Scopus subject areas

  • Genetics

Cite this

Loiler, S. A., Conlon, T. J., Song, S., Tang, Q., Warrington, K. H., Agarwal, A., ... Flotte, T. R. (2003). Targeting recombinant adeno-associated virus vectors to enhance gene transfer to pancreatic islets and liver. Gene Therapy, 10(18), 1551-1558. https://doi.org/10.1038/sj.gt.3302046

Targeting recombinant adeno-associated virus vectors to enhance gene transfer to pancreatic islets and liver. / Loiler, S. A.; Conlon, T. J.; Song, S.; Tang, Q.; Warrington, K. H.; Agarwal, A.; Kapturczak, M.; Li, C.; Ricordi, Camillo; Atkinson, M. A.; Muzyczka, N.; Flotte, T. R.

In: Gene Therapy, Vol. 10, No. 18, 01.09.2003, p. 1551-1558.

Research output: Contribution to journalArticle

Loiler, SA, Conlon, TJ, Song, S, Tang, Q, Warrington, KH, Agarwal, A, Kapturczak, M, Li, C, Ricordi, C, Atkinson, MA, Muzyczka, N & Flotte, TR 2003, 'Targeting recombinant adeno-associated virus vectors to enhance gene transfer to pancreatic islets and liver', Gene Therapy, vol. 10, no. 18, pp. 1551-1558. https://doi.org/10.1038/sj.gt.3302046
Loiler, S. A. ; Conlon, T. J. ; Song, S. ; Tang, Q. ; Warrington, K. H. ; Agarwal, A. ; Kapturczak, M. ; Li, C. ; Ricordi, Camillo ; Atkinson, M. A. ; Muzyczka, N. ; Flotte, T. R. / Targeting recombinant adeno-associated virus vectors to enhance gene transfer to pancreatic islets and liver. In: Gene Therapy. 2003 ; Vol. 10, No. 18. pp. 1551-1558.
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