Modulating Transcription with Artificial Regulators

Many human diseases are characterized by altered gene expression patterns caused by malfunctioning transcriptional regulators. This has inspired intense interest in the development of artificial transcription factors that regulate the expression of specific genes either positively or negatively. Particular success has been achieved through the use of DNA-binding molecules such as triplex-forming oligonucleotides, peptide nucleic acids, and polyamides that upregulate transcription in vitro and, in some cases, in cell culture. Despite impressive advances in the last decade, however, artificial transcription factors that reconstitute all of the functions of natural regulators are not yet a reality. In particular, it has proven difficult to design artificial transcription factors composed entirely of non-natural components. Such factors will be powerful chemical tools for unraveling the mechanisms of transcriptional regulation and in the long term offer considerable therapeutic potential.