Click-constructed modular signal aptamer chimeras enable receptor-independent degradation of membrane proteins.

ABSTRACT: Cell-membrane proteins are critical mediators of signal transduction, playing essential roles in disease occurrence and progression. The emerging LYTACs (Lysosome-targeting chimeras) technology combines drug-targeting strategies with lysosomal degradation, providing a novel approach to drug development and offering new possibilities for disease therapy. However, the clinical applicability of current LYTAC degraders is limited by the variable expression of lysosome-targeting receptors (LTRs) in tissues. To overcome this limitation, we herein hijacked a YXXØ sorting signal that derived from lysosome-associated membrane protein 2a (LAMP-2a) to develop a signal aptamer platform (SApt), which exhibits high specificity for targeting membrane proteins and inducing efficient lysosomal degradation.

SUBMITTER: Xie W 

PROVIDER: S-EPMC12130886 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature