By using both in vivo and in vitro experimental systems, the principal features of the conventional AAV rescue model have been shown to include the synthesis of duplex linear replicative forms that are self priming by virtue of terminal hairpin palindromes. Two sort of mechanisms have been proposed to explain rescue of AAV in human cells: rescue may be carried out by repair cellular nucleases or it may be coupled to DNA replication. It has been observed that rescue of the AAV genome from a plasmid may be carried out by a Holliday structure-resolving activity in vitro and in vivo. In any case, the episomal DNA is not produced by the ����AAV rolling hairpin���� type of DNA replication because,when we analyzed the structure of low Mr DNA ASP1517 molecules we did not observe the canonical AAV replicative intermediates, but rather the supercoiled, nicked circular replicated plasmid and the ssDNA. Moreover, these molecules contain not only ITRs and URA3 sequences, but also vector sequences. This observation suggests that the entire plasmid is replicated as circle from which ssDNA is released. To explain the production of ssDNA genomes without generating linear duplex intermediate, we propose a model outlined in figure 8. According to our model, Rep68 binds the ITR at the RBE element and nicks one strand at the level of trs. The nick creates a free 39-OH end from which DNA replication is initiated. As the replication passes through the body of ITR , the partially single stranded template strand will fold into a hairpin configuration. This folding of the ITR template may be supported by Rep binding to the tip of the hairpin loop of the ITR.This event produces a strand switch and the template is likely to be the nicked strand and not the complementary one. The replication fork proceeds through the vector sequence and terminate when reaches the nicked ITR. A second nick by Rep protein occurs at the level of the newly synthesized ssDNA that is, subsequently, displaced by the helicase activity of Rep proteins. The ssDNA Navitoclax molecule containing the entire plasmid sequence is nicked by Rep protein. The final products are two ssDNA molecules containing only one ITR; one with vector sequences and one with rep and URA3 genes. Our model predicts that the resulting ssDNA genome with AAV sequences has a complete ITR only at the 59 end while the 39 end carries only a D element. The missing ITR, however, can be repaired via a gene correction mechanism described by Samulski et al..