Controllable multivalent LYTACs enhance targeted protein degradation

We present a versatile DNA-based LYTAC framework that allows control over the valency of chimeras and the distance between ligands through DNA self-assembly. By evaluating the degradation capabilities of LYTACs with 1, 3, and 9 valences, we confirm the broad applicability of the multivalent enhancement effect across different lysosome-targeting receptor-mediated degradation pathways. Our findings provide valuable insights into improving the degradation efficiency of LYTACs.