Retroviruses like HIV-1 must integrate a copy of their viral genome into the host genome. The viral protein integrase joins the 3’ ends of viral DNA to host chromatin, but how does integrase choose the integration site? For gene therapy vectors, can we direct retroviral integration to a specific site? We are using a variety of biochemical, cellular, and single molecule microscopy techniques to investigate these questions. Our recent data suggests that integration complexes move rapidly on naked DNA and need a molecular “speed bump” to pause and complete integration. This concept suggests we may be able to direct site specific integration by adding an “anchor” to integrase In order to direct integration to specific sites, we are attempting to add an “anchor” to integrase to make the protein pause and perform integration.

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