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（由申请人提供）：微阵列分析与新的统计工具结合使用，是研究基因表达的强大技术。他博士在实验室成功应用了这种方法，以分析IFN诱导的人类PBMC的表达。 Pontzer博士创建了单个氨基酸（AA）取代的IFN，这些IFN被发现具有独特的生物活性组合。微阵列分析在这些新型IFN中的应用可能会提供有关抗病毒活性（AV），抗增殖活性（AP）和毒性的基因的信息。 特别是Pontzer博士报告了几个单个AA取代，将IFNα序列插入IFN TAU（一种无毒1型IFN）。据报道，突变体的集合将AP，AV和毒性分开。据报道，一种替代（LFN TAU 26 p：L）产生具有良好AV活性的IFN-TAU，并且与IFN-Alpha相当，但不是IFN-Alpha典型的毒性。与他们的AP相比，其他人的AV较低。 这项工作将扩展我们对IFN作用的理解，对这些新型干扰素的生物学特性独立确认，并为开发和测试具有医学重要的IFN和IFN的工具提供了一种工具。至少一个已经合成的新型IFN就是这样的候选分子。