Salk Institute

Technologies Available for Licensing

Assay for Integration Inhibitors Using Pre-Integration Complexes

Inventors: Frederic Bushman, Tal Kafri, Mark Hansen
Potential Uses: Infection, HIV, Drug Discovery
A screen for viral integrase inhibitors

The invention describes an assay for viral integration inhibitors using pre-integration complexes (PICs). A cell line expressing high titers of HIV-based vectors has been developed. The vector particles produced have been used to generate PICs containing HIV integrase and other HIV proteins. This technique provides a source of PICs that are much safer to handle than live virus derived from Molt IIIB. Integrase is one of three enzymes encoded by HIV. Inhibitors of reverse transcriptase and protease have been shown to be effective in treatment of HIV infection. Similarly integrase is a promising, non-toxic target for drug therapy since there are no similar proteins known to be important for normal cell function. Despite extensive efforts, no clinically useful integrase inhibitors have been developed. In this invention, vector-based PICs were used to devise a microtiter plate-based assay for integration directed by PICs. The response to inhibitors by PICs is more authentic than purified recombinant integrase making them attractive for use in screens for inhibitors. Purified integrase protein can be inhibited by diverse compounds, complicating the identification of promising leads. However, assays with PICs are more resistant to inhibition and display a response that more closely matches the response of virus in vivo. Microtiter assay results can be obtained by PCR and gel analysis or use of the TaqMan gene quantification method.

Salk No: S97022B
Patent Status: U.S. Patent No. 6,727,058 issued April 27, 2004
Canada and Japan pending
Publications: Nat Biotechnol 17(6):578-82 (June 1999)
License Terms: Exclusive, Partially Exclusive, Nonexclusive license negotiable
Contact: Michelle Booden, Ph.D., Director of Licensing, 858.453.4100 x1612, mbooden@salk.edu

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