Fig. 1

A Genome structure of wild-type AAV and recombinant AAV. Wild-type AAV genomes consist of inverted terminal repeats (ITRs) that flank two open reading frames (ORFs), rep and cap. To generate recombinant AAV, the rep and cap genes are deleted between the ITRs, followed by the insertion of a transgene of interest at the deletion site. In trans, the rep and cap functions are implemented when the viral vector is manufactured. Rep58 and Rep68 are encoded by the p5 promoter, whereas Rep52 and Rep40 are encoded by the p19 promoter as part of the structure of the wild-type AAV genome. The assembly-activating protein (AAP), VP1, 2, and 3 are all translated from the p40 transcript encoded by the cap gene. Recombination is possible between AAV vectors carrying DNA sequences that are homologous to a particular chromosomal site and the corresponding genomic locus. loxP (locus of X-over P1) is a 34-bp site located on the bacteriophage P1. The site comprises an 8-base asymmetric sequence, variable except for the middle two bases, situated between two sets of 13-base symmetric sequences. The bacteriophage P1 life cycle depends on LoxP sites, which are essential for phage genome integrity and facilitating phage integration into the bacterial chromosome at the loxB target site (approximately every 90 kbp) [23,24,25,26]