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The aptamer-based RNA-PROTAC
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DOI：10.1016/j.bmc.2023.117299.png)
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Abstract
En 中文
RNA-binding proteins (RBPs) dysfunction has been implicated in a number of diseases, and RBPs have tradi-tionally 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 hetero-bifunctional 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.
Keywords:
Targeted degradation
RNA-binding proteins
Aptamer-based RNA-PROTAC
Heterobifunctional molecule
Journal
B
IF:
3
Papers:
1.7W
Citations:
2.7W