Persistence of rAAV vectors

In most in vitro and in vivo applications of rAAV, it has been observed that rAAV vector genomes persist long-term, in most cases for the life span of the infected cell. This persistence may be viewed as a modified form of latent AAV infection. Given the pivotal role played by the Rep proteins in the site-specific integration of wild-type AAV, it is not surprising that Rep-deleted rAAV 

ADENO-ASSOCIATED VIRAL VECTORS FOR GENE THERAPY 

The important contribution of these episomal forms to transgene expression has recently been demonstrated in mouse fiver (Nakai et al., 2001). In this study a partial hepatectomy was performed on mice after portal vein injection of a rAAV vector, in order to stimulate proliferation of the transduced fiver. In this situation one would predict that expression from integrated vector genomes would not decrease significantly, since the genome copy 

The predominance of episomal persistence in latent rAAV infection has a number of important implications. First, it helps to explain why rAAV gene transfer has been particularly effective in terminally differentiated nonproliferating cell populations. In these cells episomal forms are quite stable and are not diluted out by host cell division. A second important aspect of episomal persistence is that this mode of persistence decreases the risk of insertional mutagenesis that might otherwise be associated with random integration of vector DNA into the host cell genome. 

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