SBIR Phase II: Bioinformatic Data Mining for AIDS Resistance Genes

这个小型企业创新研究（SBIR）二期项目的重点是使用新的基于进化的数据挖掘软件来发现目前难治性疾病的人类治疗方法的发展目标。第一阶段表明，基于进化的数据挖掘软件对于显著缩小寻找蛋白质的范围是有用的，这些蛋白质使黑猩猩在感染HIV-1后对艾滋病的进展具有抵抗力。在第二阶段，将评估转染了编码一种适应黑猩猩蛋白质的基因的人类细胞系对体外HIV-1感染的影响。在HIV-1感染的人类细胞中，筛选其他黑猩猩同源基因的差异调节将继续确保所有潜在的艾滋病抗性蛋白已被确定。经过改造的黑猩猩基因/蛋白质将与至少10年内HIV-1感染未发展为艾滋病的人类基因/蛋白质进行比较，看看是否有任何共同点。这项技术的商业应用是对抗艾滋病。经过适应性进化的蛋白质的鉴定将导致药物介导HIV-1感染的进展。同样的方法可能对其他几种难治性疾病有更广泛的影响，而非人类灵长类动物比人类更不易感染这些疾病。这包括丙型肝炎、败血症、1型糖尿病和某些癌症。

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.