Adeno‐associated virus‐mediated gene transfer

AbstractAlthough the remarkable versatility and efficacy of recombinant adeno‐associated virus 2 (AAV2) vectors in transducing a wide variety of cells and tissues in vitro, and in numerous pre‐clinical animal models of human diseases in vivo, have been well established, the published literature is replete with controversies with regard to the efficacy of AAV2 vectors in hematopoietic stem cell (HSC) transduction. A number of factors have contributed to these controversies, the molecular bases of which have begun to come to light in recent years. With the availability of several novel serotypes (AAV1 through AAV12), rational design of AAV capsid mutants, and strategies (self‐complementary vector genomes, hematopoietic cell‐specific promoters), it is indeed becoming feasible to achieve efficient transduction of HSC by AAV vectors. Using a murine serial bone marrow transplantation model in vivo, we have recently documented stable integration of the proviral AAV genome into mouse chromosomes, which does not lead to any overt hematological abnormalities. Thus, a better understanding of the AAV–HSC interactions, and the availability of a vast repertoire of novel serotype and capsid mutan