HSV/AAV hybrid vectors

Site-specific integration at a well defined locus on the host genome is considered highly desirable in gene therapy to maintain gene stability and avoid oncogenic events. Adeno-associated virus (AAV) offers a unique strategy to achieve this. The AAV Rep78/68 proteins and the two ITRs that flank the AAV genome are sufficient to accomplish integration of transgene DNA into the AAVS1 site on human chromosome 19. We have developed HSV/AAV hybrid vectors that combine the large transgene capacity of HSV-1 with the capability for site-specific genomic integration of AAV. These hybrid vectors can be packaged into HSV-1 virions and, following infection of cells, mediate the insertion of transgene sequences of up to 100 kbp into AAVS1 and support long-term transgene expression.

Funding: SNF, NIH

Selected Publications