Plastid-Based Production of Recombinant Proteins: Advancing Toward Global Health Applications.

Plastid-based production of recombinant proteins has emerged as a transformative platform for global health applications, offering high-yield, low-cost, and scalable alternatives to conventional microbial and mammalian systems. Chloroplasts facilitate exceptional transgene expression (often exceeding 40% of total soluble protein (TSP)), due to leveraging high genome copy numbers per cell, precise multi-gene stacking, minimal position effects, and maternal inheritance for biocontainment. Critically, recent advances have progressed beyond proof-of-concept. 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-term stability, and batch-to-batch consistency, with multiple candidates having received FDA approval to enter human clinical trials. Furthermore, marker-free engineering strategies have effectively addressed longstanding biosafety concerns, enabling the development of commercial-grade lines. This review synthesizes these breakthroughs and highlights how plastid technology is being strategically advanced toward equitable, oral-delivery solutions for vaccines, enzyme replacement therapies, and chronic disease management globally.