Gene Expression Assays of Natural and Mutant Type I IFN

描述(申请人提供)：微阵列分析与新的统计工具相结合，是研究基因表达的一项强大的技术。何博士在他的实验室中成功地应用了这种方法来分析干扰素诱导的人外周血单核细胞的表达。庞策博士创造了单一氨基酸(AA)取代的IFN，已被发现具有独特的生物学活性组合。将微阵列分析应用于这些新型的干扰素，可能会提供与抗病毒活性(AV)、抗增殖活性(AP)和毒性相关的基因的信息。具体地说，庞策博士报告了几个将干扰素α序列插入干扰素tau(一种无毒的1型干扰素)的单一AA替代。据报道，突变株的收集可以分离AP、AV和毒性。据报道，一个替换(LFN tau 26 P：L)产生了具有良好AV活性的干扰素-tau，其AP相当于干扰素-α，但没有干扰素-α的典型毒性。其他人与他们的AP相比，AV较低。这项工作将扩大我们对干扰素作用的理解，为这些新型干扰素的生物学特性提供独立的确认，并为开发和测试具有重要医学意义的干扰素和干扰素样药物提供工具。至少有一种已经合成的新型干扰素是这样的候选分子。

DESCRIPTION (provided by applicant): Microarray analysis, in combination with new statistical tools, is a powerful technology for studying gene expression. Dr. He has successfully applied this approach in his lab to analyze IFN-induced expression in human PBMCs. Dr. Pontzer has created single amino acid (AA) substituted IFNs that have been found to have unique combinations of biologic activities. The application of microarray analysis to these novel IFNs may provide information concerning the genes involved in the anti-viral activity (AV), anti-proliferative activity (AP) and toxicity. Specifically Dr. Pontzer has reported several single AA substitutions that insert IFN alpha sequence, into IFN tau (a non-toxic type 1 IFN). The collection of mutants is reported to separate AP, AV, and toxicity. One substitution (LFN tau 26 P:L) is reported to produce an IFN-tau with good AV activity and AP equivalent to IFN-alpha, but not the toxicity typical of IFN-alpha. Others have low AV compared to their AP. This work will extend our understanding of IFN action, provide independent confirmation of biologic properties of these novel interferons, and provide a tool for developing and testing medically important IFNs and IFN like drugs. At least one novel IFN already synthesized is one such candidate molecule.