Destruction of DNA‐Binding Proteins by Programmable Oligonucleotide PROTAC (O'PROTAC): Effective Targeting of LEF1 and ERG (Adv. Sci. 20/2021)

Proteolysis‐Targeting Chimera Technology In article number 2102555, Hong‐yu Li, Haojie Huang, and co‐workers demonstrate a new approach, oligonucleotide‐based proteolysis‐targeting chimera (O'PROTAC), to degrade “undruggable” transcriptional factors (TFs) via the ubiquitin‐proteasome system. O'PROTAC is designed by employing the TF‐uniquely‐recognized DNA sequence as natural “ligand”. The programmability of O'PROTAC makes it an attractive arsenal to target TFs for treatment of diseases including cancer. [Image: see text]