Spatiotemporally controlled lysosome-targeted protein degradation platforms

Lysosome-targeted protein degradation expands the druggable proteome, yet the translation of its chimeras is hindered by delivery barriers that render their in vivo performance spatiotemporally uncontrolled. 

Lysosome-targeted protein degradation platforms, which include chimeric-bifunctional and lysosome targeting receptor-independent monofunctional ones, spatiotemporally control lysosome-targeted protein degradation through various strategies.

Monofunctional lysosome-targeted protein degradation platforms feature lysosome-targeting receptor independence, simple architecture, and modularity and have recently gained widespread attention.

Given stricter spatiotemporal control requirements, lysosome-targeted protein degradation platforms operate according to unique principles: extracellularly, ensuring efficient protein of interest/lysosome targeting receptor engagement and timely degrader activation; intracellularly, preventing protein of interest recycling and lysosomal escape.

Lysosome-targeted protein degradation platforms are evolving from passive vehicles into active controllers of synergistic therapy through the integration of lysosome targeted protein degradation with immunoactivation, metabolic intervention, and gene silencing for precision medicine.

https://www.cell.com/trends/pharmacological-sciences/fulltext/S0165-6147(26)00176-8

https://sciencemission.com/Lysosome-targeted-protein-degradation