Surrogate genetics target characterization method

Abstract

A two-step, scalable method is described for identifying the cellular function(s) of one or more genes of unknown function, and for identifying modulators of the gene(s). The method uses the reversal or alteration of a phenotype created by the expression of the heterologous gene, e.g., a human gene, to identify modulators of that gene's activity. That modulator is then used in an in vitro or in vivo disease model system to identify compounds which affect disease progression. The subset of compounds which influence disease in a therapeutic manner are drug leads. However, all compounds which influence disease progression are tools to at least partially characterize gene function. The inhibitor identification step of the method is preferably carried out using a plurality of microbial strains or cell lines expressing different heterologous DNA sequences in a single solution. The method is particularly useful for genes which have not been validated as good inhibitor targets.