Chip-Based Synthetic Biology to Track Anticancer Drug Activity$\backslash $fs20

It is advantageous to develop systems that represent significant complexity of biological systems, while maintaining control over specific factors involved in a particular process. We have established a chip-based electrochemical platform for following the repair of DNA damage produced by a redox-cycling anticancer drug, beta-lapachone($\beta $-lap). These chips, which possess key features to reproduce the cellular environment, drug cofactors, and base-excision repair (BER) enzymes tracked DNA damage repair activity with redox probe-modified DNA monolayers on gold. We were able to observe drug-specific changes in the square wave voltammetry at therapeutic drug concentrations with high statistical significance over drug-free control. We also demonstrate high correlation of this change with the specific drug cycle through rational controls. Thus, this chip-based platform enabled tracking of drug-induced damage repair processes when biological criteria were met, providing a unique synthetic platform for uncovering activity normally restricted to inside cells.