Gene Expression Assays of Natural and Mutant Type I IFN

天然和突变 I 型干扰素的基因表达测定

• 批准号: 6742226
• 负责人: FLOYD E TAUB
• 金额: $ 10万
• 依托单位: LIFETIME PHARMACEUTICALS, INC.
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-05-06 至 2005-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6742226
• 关键词: aminoacid; antineoplastics; antiviral agents; biotechnology; biotherapeutic agent; complementary DNA; cytotoxicity; gene expression; gene expression profiling; immunogenetics; immunologic substance development /preparation; interferon alpha; interferons; microarray technology; mutant; peptide analog; protein structure function; therapy adverse effect

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.

描述（申请人提供）：微阵列分析与新的统计工具相结合，是研究基因表达的强大技术。贺博士已经在他的实验室中成功地应用了这种方法来分析ifn诱导的人类PBMCs表达。Pontzer博士创造了单氨基酸（AA）取代的ifn，这些ifn已被发现具有独特的生物活性组合。应用微阵列分析这些新型ifn可能提供有关抗病毒活性（AV）、抗增殖活性（AP）和毒性相关基因的信息。具体来说，Pontzer博士已经报道了几个将IFN α序列插入IFN tau（一种无毒的1型IFN）的单个AA替换。据报道，突变体的收集可以分离AP、AV和毒性。据报道，一种取代（LFN tau 26 P:L）产生的IFN-tau具有良好的AV活性和相当于ifn - α的AP，但没有ifn - α的典型毒性。与AP相比，其他的AV较低。这项工作将扩展我们对IFN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，并为开发和测试医学上重要的IFN和IFN类药物提供工具。至少有一种已经合成的新型干扰素就是这样一种候选分子。