AAV vector integration sites in mouse hepatocellular carcinoma

A Donsante, DG Miller, Y Li, C Vogler, EM Brunt… - Science, 2007 - science.org
A Donsante, DG Miller, Y Li, C Vogler, EM Brunt, DW Russell, MS Sands
Science, 2007science.org
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 …
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.
AAAS