This Small Business Innovation Research (SBIR) Phase II project focuses on the use of novel evolution-based data mining software to discover targets for the development of human therapeutics for currently intractable diseases. Phase I demonstrated that the evolution-based data-mining software was useful for dramatically narrowing the search for proteins that make chimpanzees resistant to the progression of AIDS after infection by HIV-1. In Phase II, the impact on in-vitro HIV-1 infectivity of a human cell line transfected with the gene encoding one of the adapted chimpanzee proteins will be assessed. Screening of other chimpanzee homologs of genes differentially regulated in human cells upon HIV-1 infection will continue to ensure that all potential AIDS resistance proteins have been identified. The adapted chimpanzee genes/proteins will be compared to those from humans in which HIV-1 infection has not progressed to AIDS for at least 10 years to see if there are any commonalities.
The commercial application of this technology is in the battle against AIDS disease. The identification of proteins that have undergone adaptive evolution should lead to drugs to mediate the progression of HIV-1 infection. This same approach may have broader impact against several other intractable diseases for which non-human primates are less susceptible than humans. This includes hepatitis-C, sepsis, type-1 diabetes, and certain cancers.
