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2025. 03Oligo Pools

A new strategy to HER2-specific antibody discovery through artificial intelligence-powered phage display screening based on the Trastuzumab framework

Mancang Zhang, Qiangzhen Yang, Jiangrong Lou, Yang Hu, Yongyong Shi

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ABSTRACT

Human epidermal growth factor receptor 2 (HER2) is a recognized drug target, and it serves as a critical target for various cancer treatments, necessitating the discovery of more antibodies for therapeutic and detection purposes. Here, we have developed an innovative workflow for antibody generation through Artificial Intelligence-powered Phage Display Screening (AIPDS). This workflow integrates artificial intelligence-driven antibody CDRH3 sequence design, high-throughput DNA synthesis and phage display screening. We applied AIPDS workflow to generate promising antibodies against the human epidermal growth factor receptor 2 (HER2), offering a template for streamlined antibody generation. Seven novel antibodies stood out, demonstrating promising efficacy in various functional assays. Notably, DYHER2–02 demonstrates strong performance across all experimental tests. In summary, our study introduces a novel methodology to generate new antibody variants of an existing antibody using an AI-assisted phage display approach. These new antibody variants hold potential applications in research, diagnosis, and therapeutic applications.

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