The investigators propose to develop retroviral derivatives capable of integrating into preselected DNA sites. They have previously reported the construction and characterization of a fusion protein composed of HIV integrase linked to the site specific DNA-binding domain of l repressor. This hybrid protein directed integration selectively to target DNAs containing sites recognized by the repressor domain. More recently they have found that i) they can create biologically active HIV proviruses encoding integrases fused to DNA-binding domains, and ii) preintegration complexes containing such fusions direct integration preferentially into target DNA containing appropriate sites.
