Molecular pharming in cereal crops

Abstract

There are many different agricultural expression systems that can be used for the largescale production of recombinant proteins, but fieldgrown cereal crops are among the most attractive because recombinant proteins can be targeted to accumulate in the seed, and specifically in the endosperm, which has evolved naturally as a protein storage tissue. Within the developing endosperm, proteins are supplied with molecular chaperones and disulfide isomerases to facilitate folding and assembly, while the mature tissue is desiccated to prevent proteolytic degradation. Proteins expressed in cereal seeds can therefore remain stable for years in ambient conditions. Recent basic research has revealed a surprising diversity of protein targeting mechanisms in the endosperm, which can help to control posttranslational modification and accumulation. Applied research and commercial development has seen several pharmaceutical proteins produced in cereals reach late stage preclinical development and the first clinical trials, with a number of companies now dedicated to developing cereal-based production platforms. In this review we discuss the basic science of molecular pharming in cereals, some of the lead product candidates, and challenges that remain to be addressed including the emerging regulatory framework for plant-made pharmaceuticals.

Expression of a Functional Recombinant Human Basic Fibroblast Growth Factor from Transgenic Rice Seeds

“…Therefore, rice endosperm is considered to be a favorable expression platform for large-scale production of pharmaceutical proteins. The advantages are attractive for both research and industrial applications [16]. …”

Transgenic crops for the production of recombinant vaccines and anti-microbial antibodies

“…78 The US biotechnology company Ventria Bioscience, which uses rice to produce the antibacterial, antiviral and antifungal proteins lactoferrin and lysozyme, as well as human serum albumin for medical use, have gained regulatory approval for these products from the USDA. 79 Edible seeds have GRAS status (meaning they are 'generally regarded as safe' for human consumption and do not need further safety testing) making them particularly suitable for the development of oral vaccines that can be administered as flakes or flour with minimal purification. Clinical studies involving ETEC antigens produced in maize seeds have been successful, and Tokuhara et al have developed a cost-effective CTB vaccine produced in the protein storage organelles of rice seeds (MucoRice-CTB) which provided specific long-term protection against cholera in mice and macaques.…”

Comparison of expression systems for the production of human interferon-α2b

“…The prime decision criteria for the choice of an expression system in pharmaceutical production are the safety of the yielded protein in context with the post-translational modification pattern, followed by overall cost, production timescale, scale up capacity, product quality and storage cost [10,12,[27][28][29]. All plant expression platforms, including whole plants systems, have safety benefits over expression platforms based on microbial cells.…”