Targeting Retroviral Integration

Retroviral vectorsarecurrently themost widely used method ofgenetransfer ingene therapy, inpartbecause theretroviral integration systemprecisely links thetherapeutic sequencestothehost chromosome with neat covalent bonds. DNA integration, however, comes with aprice. Retroviral integration systemsshowlittle targetsite specificity, andhaphazard insertions into a patient's chromosomes can createproblems. Integration nearcellular proto-oncogenesmay lead toectopic gene activation andcancer,not a desirable outcome of gene therapy (1).Retroviral integration can also inactivate genes(2). Recent findings on site-specific DNA integration by retroviruses andretrotransposons suggesta strategyforretrovirusbased gene therapy thatavoids