Steve Zhang

302. Engineered Zinc Finger Transcription Factors: A Platform for Therapeutic Gene Regulation with Exquisite Specificity

A challenge of modern medicine is the development of effective yet highly specific drugs. To this end, we are developing artificial zinc finger protein transcription factors (ZFP TFs) as direct therapeutic agents for the treatment of disease. Here we show that ZFP TFs can be designed to activate or repress a wide range of clinically relevant genes, including Phospholamban, a regulator of heart contractivity, Chk2, a kinase with a role in DNA damage pathway and P2X7, a ligand-gated channel. Moreover, using these examples and the Affymetrix GeneChipR platform we show that these ZFP TFs regulate the targeted gene with exceptional and often singular specificity genome wide, despite the complexity of mammalian genome. This exquisite specificity is independent of both gene target and species, while occurring in the context of maximal efficacy. This combination of potency and specificity supports the clinical potential of ZFP TF technology.