Site-specific integration of a transgene mediated by a hybrid adenovirus/adeno-associated virus vector using the Cre/loxP-expression-switching system

As vectors, adenoviruses (Ads) have many attractive advantages for in vivo gene therapy. However, Ads do not usually integrate into the host genome an d gene expression is, thus, transient. Adeno-associated virus (AAV) integra tes into a specific locus (AAVS1) on the human host's chromosome 19, while conventional recombinant AAV (rAAV) vectors do not possess this property be cause such vectors lack the rep gene. AAV vectors carrying the rep gene do not have enough space for insertion of a transgene. We have constructed a h ybrid adenovirus/adeno-associated virus (Ad/VAAV) vector which has the adva ntages of both Ads and AAVs. Given that the rep gene products inhibit propa gation of Ads, we used the Cre/loxP-expression-switching system to regulate the expression of the rep gene. The Ad/AAV vector easily propagates, can e fficiently infect a broad range of cell types, and can integrate into a spe cific locus on host chromosomes. (C) 2000 Academic Press.