The historical evolution of CHO cell line development for biologics production: 60 years and still counting.

Abstract

Chinese Hamster Ovary (CHO) cells have played a central role in the production of therapeutic proteins since their initial isolation in the 1950s. Over the decades, scientific innovations have transformed CHO cells into the powerhouse of the biopharmaceutical industry. From rudimentary culture conditions and random integration of transgenes into the host genome, to synthetic biology, genetic engineering, high-performing chemically defined media, targeted transgene integration and AI-driven cell line development strategies, each decade has introduced transformative tools, knowledge, and insights to improve CHO cell line development and characterization processes. This review outlines the chronological history of the CHO cell line development process, decade by decade, highlighting central milestones and innovations, technological breakthroughs, and the role of key innovative steps that have enabled modern cell line development workflows and ultimately the industrial-scale manufacturing of biologics.