# DNA Tweezers with Replaceable Clamps for the Targeted Degradation of Cell Membrane Proteins

## TL;DR

This paper introduces DNA tweezers with replaceable clamps that can efficiently target and degrade specific cell membrane proteins in cancer cells.

## Contribution

The novel DNA tweezers with replaceable clamps enhance the specificity and efficiency of membrane protein degradation.

## Key findings

- Lysis was verified in multiple tumor cell lines.
- Antitumor activity was confirmed in zebrafish models.
- The tweezers offer a versatile strategy for degrading disease-causing proteins.

## Abstract

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.