Article Summary 25/11/22
Article title
Development of a targeted BioPROTAC degrader selective for misfolded SOD1
Journal
Nature communications
Tags
Gene therapy; BioPROTAC; Degenerative disease
Introduction
ALS, a critical neurodegenerative disease, is relevant with protein misfolding and aggregation. SOD1 gene is related to over 200 ALS-correlated mutation, thus targeting SOD1 might be an applicable strategy to treat ALS. Target protein degradation is an attractive therapy to target undruggable targets. Recently, a gene therapy called BioPROTAC, fusing E3 catalytic domain and target binder, has emerged as a potential TPD approach. This work aimed to screen a BioPROTAC to target SOD1.
This work
This work designed a BioPROTAC to fuse misfolded SOD1 antibody ScFv and E3 catalytic domain to mediate target protein degradation. They first proved BioPROTAC bound misfolded SOD1 but not correctly folded SOD1. Subsequently, they explored the pathway of BioPROTAC-mediated SOD1 degradation. Finally, they found the BioPROTAC they designed could alleviate the symptom of xenograft mice with ALS disease and decrease the SOD1 aggregation of mouse brain.
doi
10.1038/s41467-025-65481-w