Identification of liver-specific enhancer-promoter activity in the 3’ UTR of the wild-type AAV2 genome. Adeno-associated virus

We describe and functionally characterize a previously unknown liver-specific enhancer-promoter element in the wild-type AAV2 (wtAAV2) genome lying between the cap stop codon and right-hand inverted terminal repeat (ITR). Remarkably, this element falls within the 163-nucleotide common insertion region of the AAV genome implicated in HCC oncogenesis, thereby providing a mechanistic explanation for the participation of AAV integration events in the development of HCC. Overall design: In vitro and in vivo assays demonstrate activity of the enhancer-promoter element in murine and human hepatocytes. An in vitro assessment of wtAAV2 infection demonstrates transcription from the negative strand of the AAV genome.