Journal Article

Engineering the Plant Secretory Pathway for the Production of Next-Generation Pharmaceuticals

Meyers, Ann E., Margolin, Emmanuel A., Chapman, Ros, Strasser, Richard, Williamson, Anna-Lise, Rybicki, Edward P.

2020

Overview

Production of biologics in plants, or plant molecular pharming, is a promising protein expression technology that is receiving increasing attention from the pharmaceutical industry. Previously, low expression yields of recombinant proteins and the realization that certain post-translational modifications (PTMs) may not occur optimally limited the widespread acceptance of the technology. However, molecular engineering of the plant secretory pathway is now enabling the production of increasingly complex biomolecules using tailored protein-specific approaches to ensure their maturation. These involve the elimination of undesired processing events, and the introduction of heterologous biosynthetic machinery to support the production of specific target proteins. Here, we discuss recent advances in the production of pharmaceutical proteins in plants, which leverage the unique advantages of the technology. Plants are an alternative pharmaceutical manufacturing platform with unique advantages compared with conventional technologies.Engineering the secretory pathway in plants enables the production of biologics that would otherwise accumulate at low levels or in an improperly processed form.Host proteases can be inactivated by co-expressing broad-spectrum protease inhibitors or by manipulating the pH along the secretory pathway.Glycoengineering strategies enable the production of human-like glycoforms that can be tailored to improve their biological activity.Introducing heterologous chaperone machinery improves the production of target proteins where the endogenous machinery does not efficiently mediate folding.Furin processing and tyrosine sulfation can be achieved in planta by introducing the required biosynthetic machinery.

• Publisher: Elsevier Ltd,Elsevier Limited
• Subject: Antibodies / biologics / Biomolecules / biopharmaceuticals / biosynthesis / chaperones / cleavage / Disease / Engineering / Enzymes / folding / glycosylation / Good Manufacturing Practice / Humans / Influenza / Internal Medicine / Mammals / Manufacturing / Medical research / molecular farming / Molecular Farming - trends / Pandemics / Pharmaceutical industry / Pharmaceuticals / plant proteins / Plant Proteins - biosynthesis / Plant Proteins - genetics / Plant Proteins - therapeutic use / Plants - chemistry / Plants - genetics / Plants, Genetically Modified - genetics / Post-translation / post-translational modification / proteases / Protein Engineering - trends / Proteins / recombinant proteins / Recombinant Proteins - biosynthesis / Recombinant Proteins - genetics / Recombinant Proteins - therapeutic use / Secretory Pathway - genetics / Vaccines