Brevia

AAV Vector Integration Sites in Mouse Hepatocellular Carcinoma

Science  27 Jul 2007:
Vol. 317, Issue 5837, pp. 477
DOI: 10.1126/science.1142658

You are currently viewing the abstract.

View Full Text

Via your Institution

Log in through your institution

Log in through your institution


Abstract

Adeno-associated viruses (AAV) are promising gene therapy vectors that have little or no acute toxicity. We show that normal mice and mice with mucopolysaccharidosis VII (MPS VII) develop hepatocellular carcinoma (HCC) after neonatal injection of an AAV vector expressing b-glucuronidase. AAV proviruses were isolated from four tumors and were all located within a 6-kilobase region of chromosome 12. This locus encodes several imprinted transcripts, small nucleolar RNAs (snoRNAs), and microRNAs. Transcripts from adjacent genes encoding snoRNAs and microRNAs were overexpressed in tumors. Our findings implicate this locus in the development of HCC and raise concerns over the clinical use of AAV vectors.

    View Full Text

    Related Content