such as vaccines, antibodies and other therapeutic or prophylactic entities can be
listed. For this technology, the term plant molecular farming has been coined with
reference to agricultural applications due to the use of crops as biofactories for
the production of high-added value molecules. In this perspective, edible plants
have also been thought as a tool to deliver by the oral route recombinant compounds of medical significance for new therapeutic strategies. Despite many hurdles
in establishing regulatory paths for this “novel” biotechnology, plants as bioreactors deserve more attention when considering their intrinsic advantages, such as
the quality and safety of the recombinant molecules that can be produced and
their potential for large-scale and low-cost production, despite worrying issues
(e.g. amplification and diffusion of transgenes) that are mainly addressed by regulations, if not already tackled by the plant-made products already commercialized.
The huge benefits generated by these valuable products, synthesized through one
of the safest, cheapest and most efficient method, speak for themselves.
Milestone for plant-based recombinant protein production for human health use
was the approval in 2012 by the US Food and Drug Administration of plant-made
taliglucerase alfa, a therapeutic enzyme for the treatment of Gaucher’s disease,
synthesized in carrot suspension cultures by Protalix BioTherapeutics.
In this review, we will go through the various approaches and results for plantbased production of proteins and recent progress in the development of plant-made
pharmaceuticals (PMPs) for the prevention and treatment of human diseases. An
analysis on acceptance of these products by public opinion is also tempted.
Keywords Plant molecular farming, Plant-derived antibodies, Plant-derived
vaccines, Responsible research and innovation
1 Introduction
Plants have provided mankind with useful molecules for centuries. The idea to
produce heterologous (exogenous, non-plant) protein in plants to get plant-made
pharmaceuticals (PMPs) has been available and rapidly advanced, for just over
30 years (Ma et al. 2003). The first plant-made pharmaceutically relevant protein
was the human growth hormone, expressed in transgenic tobacco in 1986 (Barta et al.
1986). Other human proteins have been produced in an increasing variety of plant
species and of techniques. In 1989, the expression of the first antibody in tobacco
(Hiatt et al. 1989) and, subsequently, the production of the first experimental plantmade vaccine (e.g. hepatitis B virus surface antigen) (Mason et al. 1992) clearly
showed that plants had the capability to assemble functional glycoproteins with
complex structure. The structural authenticity and preservation of function of plantproduced recombinant proteins was confirmed by the production of more complex
antibody derivatives such as the secretory immunoglobulin A (Ma et al. 1995) and
new immunogenic proteins (Haq et al. 1995). Also antigenic peptides, expressed as
fusions to plant viral coat proteins, were made, and, in many cases, the assembled
viral-like particles were demonstrated able to protect animals from the challenge
66
S. Massa et al.
listed. For this technology, the term plant molecular farming has been coined with
reference to agricultural applications due to the use of crops as biofactories for
the production of high-added value molecules. In this perspective, edible plants
have also been thought as a tool to deliver by the oral route recombinant compounds of medical significance for new therapeutic strategies. Despite many hurdles
in establishing regulatory paths for this “novel” biotechnology, plants as bioreactors deserve more attention when considering their intrinsic advantages, such as
the quality and safety of the recombinant molecules that can be produced and
their potential for large-scale and low-cost production, despite worrying issues
(e.g. amplification and diffusion of transgenes) that are mainly addressed by regulations, if not already tackled by the plant-made products already commercialized.
The huge benefits generated by these valuable products, synthesized through one
of the safest, cheapest and most efficient method, speak for themselves.
Milestone for plant-based recombinant protein production for human health use
was the approval in 2012 by the US Food and Drug Administration of plant-made
taliglucerase alfa, a therapeutic enzyme for the treatment of Gaucher’s disease,
synthesized in carrot suspension cultures by Protalix BioTherapeutics.
In this review, we will go through the various approaches and results for plantbased production of proteins and recent progress in the development of plant-made
pharmaceuticals (PMPs) for the prevention and treatment of human diseases. An
analysis on acceptance of these products by public opinion is also tempted.
Keywords Plant molecular farming, Plant-derived antibodies, Plant-derived
vaccines, Responsible research and innovation
1 Introduction
Plants have provided mankind with useful molecules for centuries. The idea to
produce heterologous (exogenous, non-plant) protein in plants to get plant-made
pharmaceuticals (PMPs) has been available and rapidly advanced, for just over
30 years (Ma et al. 2003). The first plant-made pharmaceutically relevant protein
was the human growth hormone, expressed in transgenic tobacco in 1986 (Barta et al.
1986). Other human proteins have been produced in an increasing variety of plant
species and of techniques. In 1989, the expression of the first antibody in tobacco
(Hiatt et al. 1989) and, subsequently, the production of the first experimental plantmade vaccine (e.g. hepatitis B virus surface antigen) (Mason et al. 1992) clearly
showed that plants had the capability to assemble functional glycoproteins with
complex structure. The structural authenticity and preservation of function of plantproduced recombinant proteins was confirmed by the production of more complex
antibody derivatives such as the secretory immunoglobulin A (Ma et al. 1995) and
new immunogenic proteins (Haq et al. 1995). Also antigenic peptides, expressed as
fusions to plant viral coat proteins, were made, and, in many cases, the assembled
viral-like particles were demonstrated able to protect animals from the challenge
66
S. Massa et al.