RNA-binding proteins (RBPs) dysfunction has been implicated in a number of diseases, and RBPs have traditionally been considered to be undruggable targets. Here, targeted degradation of RBPs is achieved based on the aptamer-based RNA-PROTAC, which consists of a genetically encoded RNA scaffold and a synthetic heterobifunctional molecule. The target RBPs can bind to their RNA consensus binding element (RCBE) on the RNA scaffold, while the small molecule can recruit E3 ubiquitin ligase to the RNA scaffold in a non-covalent manner, thereby inducing proximity-dependent ubiquitination and subsequent proteasome-mediated degradation of the target protein. Different RBPs targets, including LIN28A and RBFOX1, have been successfully degraded by simply replacing the RCBE module on the RNA scaffold. In addition, the simultaneous degradation of multiple target proteins has been realized by inserting more functional RNA oligonucleotides into the RNA scaffold.

RNA 结合蛋白 (RBPs) 功能障碍与许多疾病有关，传统上认为 RBPs 是不可药用的靶点。在这里，基于适体的 RNA-PROTAC 实现了 RBP 的靶向降解，它由遗传编码的 RNA 支架和合成的异双功能分子组成。目标 RBP 可以结合到 RNA 支架上的 RNA 共有结合元件 (RCBE)，而小分子可以以非共价方式将 E3 泛素连接酶募集到 RNA 支架，从而诱导接近依赖性泛素化和随后的蛋白酶体介导目标蛋白的降解。不同的 RBP 目标，包括 LIN28A 和RBFOX1, 已经通过简单地更换 RNA 支架上的 RCBE 模块而成功降解。此外，通过将更多功能性 RNA 寡核苷酸插入 RNA 支架，实现了多个靶蛋白的同时降解。