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Chloroplasts facilitate exceptional transgene expression (often exceeding 40% of total soluble protein (TSP)), due to leveraging high genome copy numbers per cell, precise multi\u2010gene stacking, minimal position effects, and maternal inheritance for biocontainment. Critically, recent advances have progressed beyond proof\u2010of\u2010concept. Edible crops, such as lettuce, have been successfully producing complex human therapeutics, including fully assembled and functional blood coagulation factors, insulin precursors, and antiviral proteins, all of which remain stable and efficacious without the need for purification or cold chain storage. These products meet regulatory standards for bioburden, moisture content, long\u2010term stability, and batch\u2010to\u2010batch consistency, with multiple candidates having received FDA approval to enter human clinical trials. Furthermore, marker\u2010free engineering strategies have effectively addressed longstanding biosafety concerns, enabling the development of commercial\u2010grade lines. This review synthesizes these breakthroughs and highlights how plastid technology is being strategically advanced toward equitable, oral\u2010delivery solutions for vaccines, enzyme replacement therapies, and chronic disease management globally.<\/jats:p>","DOI":"10.1002\/biot.70212","type":"journal-article","created":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T13:50:36Z","timestamp":1773323436000},"source":"Crossref","is-referenced-by-count":2,"title":["Plastid\u2010Based Production of Recombinant Proteins: Advancing Toward Global Health Applications"],"prefix":"10.1002","volume":"21","author":[{"given":"Xuan","family":"Zhao","sequence":"first","affiliation":[{"name":"Joint International Research Laboratory of Agriculture and Agri\u2010Product Safety of the Ministry of Education of China Yangzhou University  Yangzhou China"},{"name":"College of Bioscience and Biotechnology Yangzhou University  Yangzhou 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