Mapping and sequencing the genetic blueprint in human, mice, yeast and other model organisms has created challenges and opportunities for chemistry, biology and human medicine. An understanding of the function of each of the approximately 25,000 genes in humans, and the biological circuitry that controls these genes will be driven in part by new technologies from the world of chemistry. Many cellular events that lead to cancer and the progression of human disease represent aberrant gene expression. Small molecules that can be programmed to mimic transcription factors and bind a large repertoire of DNA sequences in the human genome would be useful tools in biology and potentially in human medicine. Polyamides are synthetic oligomers programmed to read the DNA double helix. They are cell permeable, bind chromatin and have been shown to downregulate endogenous genes in cell culture.