Antiviral Drug Discovery for AIDS: The HIV-1 Vif Protein
OHSU # 0726
- David Kabat, SM.Biochemistry & Molecular Biology
- Mariana Marin, SM.Biochemistry & Molecular Biology
- Susan Kozak, SM.Biochemistry & Molecular Biology
- Kristine Rose, SM.Biochemistry & Molecular Biology
Despite remarkable medical advances, the incidence of HIV infections continues to rise throughout the world. The majority of current HIV therapies target HIV reverse transcriptase or protease, but viral resistance and toxicity have created a need for more potent and safer therapies against different viral targets.
Virion infectivity factor (Vif) is a regulatory protein produced by lentiviruses (HIV-1, HIV-2, SIV, FIV and others). Vif targets the human DNA-editing enzyme, APOBEC3G, a host defense factor which inhibits viral replication. Vif binds to APOBEC3G and prevents APOBEC3G from functioning properly in host defense. Therefore, inhibition of Vif-mediated degradation of APOBEC3G is an important new avenue for anti-HIV drug development. New therapeutic agents could inhibit Vif's function, prevent the interaction (binding) of Vif to APOBEC3G, interfere with Vif's effect APOBEC3G mRNA translation, interfere with Vif's intracellular localization of APOBEC3G, interfere with Vif production by the virus, or interfere with the targeting of Vif-associated APOBEC3G to a proteasome. Advances is the past few years have enhanced researchers'understanding of the structural and functional relationship of APOBEC3G and Vif which should help with the development of therapeutic agents which restore the anti-HIV activity of APOBEC3G or inhibit the effects of Vif.
The current technology and associated patent rights are co-owned by OHSU and the J. David Gladstone Institutes. The patent rights cover methods for identifying new drugs/agents which target Vif-mediated inhibition of APOBEC3G. Numerous possibilities for the drug/agent are covered by these patent rights as well as several ways of identifying such agents. For any organization researching, identifying and developing drugs/agents which target Vif and APOBEC3G, a license to this patent portfolio is essential.
In 2007, the HIV drug market consisted of $9.3 Billion in sales. Sales of anti-HIV drugs have expanded at a compound annual growth rate of 11.3% between 2004 and 2007 with expected sales to grow in upwards of $15.1 Billion by 2017.
Experts believe the world is about to enter a dry spell in terms of new HIV treatments. Only a few new drugs have come onto the market in recent years. The targeting of Vif-ABOBEC3G with new HIV drugs has been a relatively new area of concentration over the past few years. There are currently no inhibitors of APOBEC3G or Vif being evaluated in clinical trials, although this is an exciting area of drug research. In fact, in a February 19, 2009 interview on Drugs to Watch in 2009, David Margolis, MD, an AIDS researcher at the University of North Carolina stated that drugs that could counteract Vif have a lot of promise in the long term.
Dr. David Kabat is a Professor in the Biochemistry and Molecular Biology Department at Oregon Health & Science University. He received his B.S. from Brown University and Ph.D. from the California Institute of Technology. Prior to coming to OHSU, Dr. Kabat has held positions at MIT and the University of Oregon Medical School, now OHSU.
Issued United States Patent No. 7,220,554
United States Patent Application No. 10/865,663
United States Patent Application No. 11/671,951
United States Patent Application No. 11/671,991
United States Patent Application No. 12/471,277
Issued European Patent #1629003 in Germany, France and United Kingdom
Pending patent applications in Canada (2), Australia, Europe and Japan
Nat Med. 2003 Nov;9(11):1398-403. Epub 2003 Oct 5. HIV-1 Vif protein binds the editing enzyme APOBEC3G and induces its degradation.
The patent rights under OHSU 726 are currently available for non-exclusive licensing from OHSU.
|Issued||United States||7,220,554 B2|
|Issued||European Patent Convention||1629003|
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