Seed Expression Systems for Molecular Farming

Abstract

Plant seeds are potentially one of the most economical systems for large-scale production of recombinant proteins for industrial and pharmaceutical uses. Plant-based systems in general have several advantages over the current production systems for biopharmaceuticals, such as yeasts, fungi, insect cells, mammalian cell cultures and transgenic animals. These advantages include the ability to post-translationally modify recombinant proteins, cost-effective production of recombinant proteins, due to the ease of scale-up and the availability of established protocols for harvesting, transport, storage and processing, and a minimal possibility of product contamination by animal/human pathogens. Plant seeds have a further significant advantage, that of providing a stable repository for recombinant proteins. Despite significant progress in the use of transgenic plants and seeds for therapeutic protein production, there are still technical challenges that must be surmounted before these systems can be fully embraced as suitable, viable alternatives for large-scale ­production of biopharmaceuticals and other products. These challenges include: (1) Enhancing the yields of recombinant proteins to maximize economic feasibility; (2) Manipulating the post-translational machinery of the plant or seed so that the recombinant protein is structurally and functionally similar to the native protein; (3) Developing efficient methods for downstream processing of recombinant proteins, including the removal of any foreign amino acid motifs, in vitro post-translational processing and protein purification, and (4) Addressing regulatory issues, such as suitable mechanisms for containment of the transgenic materials to prevent inadvertent transgene flow. Considerable strides have been made toward addressing these challenges particularly in the past 5 years. This has culminated in some plant-derived pharmaceutical proteins including antibodies, vaccines, human blood products and growth regulators reaching the stage of preclinical studies or commercial development, and the promise of the first plant-made pharmaceutical glycoprotein intended for human parenteral administration. Below this progress is reviewed, with an emphasis on enhancing protein yields in seeds and controlling the N-glycan status of seed-produced recombinant proteins.