Structure of wild-type and vector AAV genomes. (A) Map of the wild-type AAV genome, including Rep (solid) and Cap (open) reading frames, promoters (p5, p19, and p40), polyadenylation site (pA), and inverted terminal repeats (ITR). The viral transcripts encoding the different Rep and Cap (VP1-3) proteins are shown below the genome. The smaller Rep proteins, VP2 and VP3, are translated from internal initiation sites. (B) Map of a typical AAV vector, showing replacement of the viral Rep and Cap genes with a transgene cassette (promoter, transgene cDNA, and polyadenylation site). (C) Secondary structure of the AAV ITR, with the locations of the Rep binding site (RBS) and terminal resolution site (TRS) indicated.