Recent progress in targeted membrane protein degradation technology based on aptamers for disease treatment

Abstract

Targeted protein degradation (TPD), a strategy currently used for treating diseases, can selectively degrade specific proteins, thereby circumventing drug resistance. Nevertheless, over 80% of the pathogenic proteins linked to human diseases, including membrane proteins, are not accessible to conventional methods. Aptamers, which are nucleic acid molecules with high affinity and specificity, are chosen from vast libraries of random sequences through in vitro screening techniques. These aptamers can effectively recognize and bind to disease-related membrane proteins, such as those associated with cancer, cardiovascular diseases, and inflammation. Consequently, aptamer-based TPD technology uses these aptamers to deliver target membrane proteins into cells, promoting their degradation and allowing for the specific elimination of pathogenic proteins. This technology showcases significant progress in overcoming the limitations of traditional small molecule inhibitors and in targeting proteins previously considered “undruggable”. In this review, we provide an overview of the latest advancements in aptamer-based TPD technology research.