Sun Yang, Huang Yichen, Chen Daiquan, Hu Shangjiu, Pan Tao, Liu Yuanding, Wang Ruowen, Tan Weihong
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.
Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), The Chinese Academy of Sciences, Hangzhou 310022, China.
Pharmaceutics. 2025 Jun 17;17(6):785. doi: 10.3390/pharmaceutics17060785.
: 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. : 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. : Lysis was verified in different tumor cell lines and the antitumor activity was confirmed in zebrafish. : 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.
细胞膜蛋白在信号转导和营养物质运输中发挥着关键作用。据报道，许多膜蛋白在癌细胞中过度表达，这与癌症进展密切相关。这些膜蛋白的靶向降解已被证明是一种有前景的肿瘤治疗策略。已经报道了几种使用适配体介导膜蛋白裂解的策略，如溶酶体介导的裂解和蛋白酶体介导的裂解，但它们的效率受到适配体与单一靶点结合亲和力的限制。我们构建了具有可替换夹子的DNA镊子，其在夹子替换后可裂解不同的蛋白质。此外，夹子通过增强特异性和提高结合亲和力提高了靶蛋白的降解效率。在不同的肿瘤细胞系中验证了裂解，并在斑马鱼中证实了其抗肿瘤活性。总体而言，这些DNA镊子提高了功能性核酸靶向递送的效率，为致病蛋白的降解提供了一种高效且通用的策略，并扩展了抗肿瘤治疗的方法。
