Vif Dimerization Antagonist: Drug Candidate against AIDS

Filed in archive Drugs, Vaccines and Therapeutics on September 5, 2005

A small fraction of HIV-positive patients do not develop full-blown AIDS, or may do so, but very slowly. A paper in the Journal of Virology have found out that such non-progressors have higher levels of an Enzyme called APOBEC-3G (A3G) in their white blood cells, and a start-up biotech company plans to begin preclinical testing on a drug designed to confer such protection on other HIV patients.

How is the drug supposed to work? It builds up on the results of Michael Malim's study on Vif as a therapeutic target. Co-author of the Virology paper Harold C. Smith, from the University of Rochester Medical Center, explains:

...A3G "edits," or introduces changes in, the HIV genetic code every time the virus copies itself. By doing so, A3G corrupts the HIV gene code and prevents the virus from reproducing. Unfortunately, HIV has evolved to counter A3G with viral infectivity factor (Vif), a protein that "grabs" A3G and tricks the body into destroying it. With the "editing enzyme" gone, HIV is free to overwhelm the immune system, leaving patients vulnerable to AIDS infections that take three million lives per year.

These findings identify a new prognostic marker for AIDS: by measuring A3G levels in HIV-infected patients, it is possible to identify non- or long-term progressors and may possibly estimate the onset of AIDS. Also, the data suggest that protecting A3G from viral attack may be an important new way to treat AIDS and other viral infections, a theory that the start-up company Oyagen Inc, would like to exploit. OyaGen's lead drug candidate, a Vif Dimerization Antagonist (VDA), prevents the two halves of Vif from linking up and leaves A3G free to "catastrophically mutate" the HIV genetic code.

OyaGen recently completed an initial $1.5 million fundraising round with investors including the technology seed fund and private individuals. The company now seeks to raise between $10 million and $30 million to fund pre-clinical trials and to support negotiations with the U.S. Food and Drug Administration on the submission of a new drug application planned for 2006.

Read the rest of the URMC press release here.