Versatile Split-and-Mix Liposome PROTAC Platform for Efficient Degradation of Target Protein <i>In Vivo</i>
Chunli Song, Zijun Jiao, Zhanfeng Hou, Yun Xing, Xinrui Sha, Yuechen Wang, Jiaxin Chen, Susheng Liu, Zigang Li, Feng Yin
Abstract
High Resolution Image Download MS PowerPoint Slide PROTAC (Proteolysis TArgeting Chimeras) is a promising therapeutic approach for targeted protein degradation that recruits an E3 ubiquitin ligase to a specific protein of interest (POI), leading to its degradation by the proteasome. Recently, we developed a novel split-and-mix PROTAC system based on liposome self-assembly (LipoSM-PROTAC) which could achieve target protein degradation at comparable concentrations comparable to small molecules. In this study, we expanded protein targets based on the LipoSM-PROTAC platform and further examined its therapeutic effects in vivo . Notably, this platform could efficiently degrade the protein level of MEK1/2 in A375 cells or Alk in NCI-H2228 cells and display obvious tumor inhibition (60–70% inhibition rate) with negligible toxicity. This study further proved the LipoSM-PROTAC’s application potentials.