Gene Expression Assays of Natural and Mutant Type I IFN

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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.