GM Plants as biofactories of pharmacutical proteins: present state and future developments

Abstract

[EN] The use of genetically modified organisms (GMOs) as biofactories for the production of recombinant proteins of commercial interest is at present one of the major applications of `molecular¿ biotechnology, and the business basis of many modern biotech companies. Since marketing in the early 1980s of recombinant human insulin, synthesised in Escherichia coli, hundreds of proteins with pharmacological activity, used for the diagnosis, treatment of prevention of human (and animal) diseases, have been produced in different platforms. The intrinsic limitations of bacterial cell cultures ¿ especially the lack of the machinery for post-translanslational modifications of proteins, which are required for the synthesis of pharmacologically active proteins ¿ have made mammalian cell cultures the system of choice for the industrial production of biopharmaceuticals. These are robust, reliable and highly controlled production systems, optimised over the years and for which GMP (`good manufacturing practice¿) procedures have been established and approved by the competent authorities. Mammalian cell cultures, however, have also important limitations and drawbacks, mostly regarding their high costs, relatively low productivity and lack of flexibility to scale-up or -down the production, in response to market demands. Many of these limitations could be overcome with the use of plant biofactories, the so-called `3rd generation¿ of genetically modified plants used for the commercial production of recombinant proteins including, more specifically, pharmaceutical proteins: `molecular pharming¿ or `pharma crops. However, despite the important advantages ¿ at least theoretically ¿ of GM plants, development of this kind of production platforms has been slow and the first plant-made biopharmaceuticals have been approved for human use only recently. This has been due mostly to regulatory issues rather than to scientific or technical problems, but recent developments indicate a rapid growth of this technology, even if it is limited to niche markets for specific plant-made protein drugs.