DNA Tweezers with Replaceable Clamps for the Targeted Degradation of Cell Membrane Proteins
Yang Sun,
Yichen Huang,
Daiquan Chen,
Shangjiu Hu,
Tao Pan,
Yuanding Liu,
Ruowen Wang,
Weihong Tan
Affiliations
Yang Sun
Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Institute of Molecular Medicine (IMM), Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
Yichen Huang
Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Institute of Molecular Medicine (IMM), Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
Daiquan Chen
Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Institute of Molecular Medicine (IMM), Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
Shangjiu Hu
Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Institute of Molecular Medicine (IMM), Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
Tao Pan
Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Institute of Molecular Medicine (IMM), Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
Yuanding Liu
Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Institute of Molecular Medicine (IMM), Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
Ruowen Wang
Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Institute of Molecular Medicine (IMM), Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
Weihong Tan
Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Institute of Molecular Medicine (IMM), Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
Background: Cell membrane proteins play crucial roles in signal transduction and nutrient transport. Many membrane proteins are reportedly overexpressed in cancer cells, which is closely related to cancer progression. The targeted degradation of these membrane proteins has been demonstrated to be a promising strategy for tumor treatment. Several strategies using aptamers to mediate membrane protein lysis, such as lysosomal-mediated lysis and proteasome-mediated lysis, have been reported, but their efficiency is limited by the binding affinity of the aptamer to a single target. Methods: We constructed DNA tweezers with replaceable clamps, which can lyse different proteins upon clamp replacement. Moreover, the clamp improved the degradation efficiency of the target proteins by enhancing the specificity and improving the binding affinity. Results: Lysis was verified in different tumor cell lines and the antitumor activity was confirmed in zebrafish. Conclusions: Overall, these DNA tweezers improve the efficiency of the targeted delivery of functional nucleic acids, provide an efficient and versatile strategy for the degradation of disease-causing proteins, and expand the approach to antitumor therapy.
