targeting oncogenic transcription
 with synthetic biologics

Transcription factors (TFs) regulate cell state by binding specific DNA sequences, thereby recruiting transcriptional machinery that either activate or repress gene expression. Due to the ubiquitous activity of TFs in all aspects of cellular function, aberrant TF activity is widely and unambiguously implicated in human disease. Modulation of TF activity therefore provides opportunities for the treatment of cancer and other forms of human disease, but, paradoxically, this class of proteins has proven resistant to the development of traditional small molecule therapies. Therefore, new classes of molecules capable of blocking the oncogenic TF activity are urgently needed. The research proposed herein will launch a novel class of synthetic inhibitors that are capable of mimicking the functional properties of a validated and so far “undruggable” oncogenic transcription factor, MYC, thus enabling targeted inhibition of MYC signaling in cancer cells dependent upon it for survival.