The development of the cell-free system (CFS) is transforming the manufacturing landscape of biomolecules with therapeutic value by providing a flexible and convenient alternative to cell-based expression systems. Compared to cell-based systems, cell-free systems offer advantages such as better modularity, greater control, and faster production because they utilize the basic transcription and translation machinery of various organisms, including Escherichia coli, wheat germ, and mammalian cells. The performance and applicability of these platforms have significantly improved in recent years through advances in synthetic biology, metabolic engineering, lyophilized formulations, and system optimization. These developments have made them more suitable for high-throughput screening and rapid prototyping, as well as on-demand biomanufacturing, especially in low-resource or emergency settings. This chapter explores the concepts, technology, engineering, and therapeutic applications of CFS. It critically examines issues related to scalability, cost-efficiency, and post-translational modifications, along with the future prospects of the field. The emerging needs combining rapid, on-demand, and personalized medicine with modern healthcare, pandemic preparedness, and decentralized bioproduction highlight cell-free systems as a vital part of the future of therapeutic development and delivery.
Keywords: Antibodies; Biomolecules; Cell-free systems; Drug development; In vitro synthesis.
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