Oral delivery of therapeutic proteins bioencapsulated in plant cells: preclinical and clinical advances.

Oral delivery of protein drugs (PDs) made in plant cells could revolutionize current approaches of their production and delivery. Expression of PDs reduces their production cost by elimination of prohibitively expensive fermentation, purification, cold transportation/storage, and sterile injections and increases their shelf life for several years. Ability of plant cell wall to protect PDs from digestive acids/enzymes, commensal bacteria to release PDs in gut lumen after lysis of plant cell wall and role of GALT in inducing tolerance facilitate prevention or treatment allergic, autoimmune diseases or anti-drug antibody responses. Delivery of functional proteins facilitate treatment of inherited or metabolic disorders. Recent advances in making PDs free of antibiotic resistance genes in edible plant cells, long-term storage at ambient temperature maintaining their efficacy, production in cGMP facilities, IND enabling studies for clinical advancement and FDA approval of orally delivered PDs augur well for advancing this novel drug delivery platform technology.