Programmable DNA Origami-Based Protease Device for Precise and Direct Proteins Degradation

-glycolic acid) to limit the protease activity. By incorporating a pH-sensitive switch and a recognition module, this system enables direct protein degradation by inducing proximity between target proteins and proteases. We demonstrate that this system specifically degrades nucleolin and PD-L1 on tumor cells under acidic conditions, exerting direct cytotoxicity on tumor cells and alleviating immunosuppression in immune cells. As a proof of concept, DOPD-mediated tumor immunotherapy was validated in a xenograft mouse model, underscoring its potential as a programmable platform for precise protein degradation.