Directed evolution of drug-like Aβ conformation-specific antibodies.

ABSTRACT: Monoclonal antibodies that recognize conformational epitopes in protein aggregates are important for research, diagnostic, and therapeutic applications related to neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. Unfortunately, it remains challenging to discover and engineer high-quality conformational antibodies that are specific for protein aggregates and possess optimal combinations of three key binding properties, namely high affinity, high conformational specificity, and low off-target binding. Here we report a directed evolution approach for generating high-quality conformational antibodies against Alzheimer's Aβ fibrils in the native IgG format. Our directed evolution approach uses targeted mutagenesis, yeast surface display, cell sorting, and deep sequencing

SUBMITTER: Desai AA 

PROVIDER: S-EPMC12554751 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature