SBIR Phase II: Bioinformatic Data Mining for AIDS Resistance Genes

SBIR第二阶段：艾滋病抗性基因的生物信息学数据挖掘

• 批准号: 0450627
• 负责人: Walter Messier
• 金额: $ 50万
• 依托单位: Evolutionary Genomics, LLC
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-15 至 2007-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0450627&HistoricalAwards=false
• 关键词: SBIR; Phase; II; Bioinformatic; Data

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.

这个小企业创新研究（SBIR）第二阶段项目的重点是使用新的基于进化的数据挖掘软件，以发现目前难治性疾病的人类疗法的发展目标。第一阶段证明，基于进化的数据挖掘软件有助于大大缩小对黑猩猩在感染HIV-1后抵抗艾滋病进展的蛋白质的搜索范围。在第二阶段，将评估用编码一种适应性黑猩猩蛋白的基因转染的人细胞系对体外HIV-1感染性的影响。对HIV-1感染后人类细胞中差异调节基因的其他黑猩猩同源基因的筛选将继续确保所有潜在的艾滋病抗性蛋白都已被鉴定。将对黑猩猩的基因/蛋白质进行比较，以确定是否有任何共同点，其中人类的HIV-1感染至少10年没有进展为艾滋病。这项技术的商业应用是在与艾滋病的斗争中。对经历适应性进化的蛋白质的鉴定应该会导致药物介导HIV-1感染的进展。同样的方法可能对其他几种难治性疾病产生更广泛的影响，这些疾病在非人类灵长类动物中比人类更不容易受到影响。这包括丙型肝炎，败血症，1型糖尿病和某些癌症。