A bioinformatic search of the genomes of chestnut blight fungus, Cryphonectria parasitica (Cp), and the Arabidopsis powdery mildew fungus, Golovinomyces cichoracearum (Gc), yielded six suspected pathogenicity genes with homologues in both species. Deletion of these genes by homologous gene replacement was attempted in Cp, with one success, TG4. The TG4-knockout strain showed changes in phenotype and reduced fungal virulence against chestnut. TG4 appears to be a promising target for host-induced gene silencing (HIGS) in transgenic American chestnut. The use of homologues from genetically tractable species like Cp can help overcome the obstacles to performing reverse genetics on intractable, biotrophic fungi such as Gc. Experiments underway involving the silencing and ectopic overexpression of the Gc homologues of the target genes provide a rapid method to study Cp genes, including to screen additional candidate genes as future targets for HIGS.