Molecular Strategies to Engineer Transgenic Rice Seed Compartments for Large-Scale Production of Plant-Made Pharmaceuticals

Abstract

The use of plants as bioreactors for the large-scale production of recombinant proteins has emerged as an exciting area of research. The current shortages in protein therapeutics due to the capacity and economic bottlenecks faced with modern protein production platforms (microbial, yeast, mammalian) has driven considerable attention towards molecular pharming. Utilizing plants for the large-scale production of recombinant proteins is estimated to be 2-10% the cost of microbial platforms, and up to 1,000-fold more cost effective than mammalian platforms (Twyman et al. Trends Biotechnol 21:570-578, 2003; Sharma and Sharma, Biotechnol Adv 27:811-832, 2009). In order to achieve an economically feasible plant production host, protein expression and accumulation must be optimized. The seed, and more specifically the rice seed has emerged as an ideal candidate in molecular pharming due to its low protease activity, low water content, stable protein storage environment, relatively high biomass, and the molecular tools available for manipulation (Lau and Sun, Biotechnol Adv 27:1015-1022, 2009).

Therapeutic properties of rice constituents and derivatives (Oryza sativa L.): A review update

“…Rice has already been used to produce such proteins as human serum albumin, antibodies, and cytokines, while some of these products have been adopted in clinical use (Greenham and Altosaar 2013). Transgenic rice expressing the neutralizing variable domain of a rotavirus-specific heavychain antibody fragment has been employed in antibody prophylaxis against rotavirus infection (Tokuhara, Alvarez et al 2013).…”

Strategies to Increase Heterologous Protein Expression in Rice Grains

“…Plant seed, and more specifically rice seed, has emerged as an ideal candidate for the large-scale production of protein therapeutics (Boothe et al 2010;Broz et al 2013;Greenham and Altosaar 2013;Kuo et al 2013;Maxmen 2012) due to its high expression capability, low protease activity, low water content, stable protein storage in ambient conditions, greater biomass, open-field production, and molecular tools available for manipulation. Because of the longer storability of rice seeds, recombinant seed banks could be generated, providing an economically feasible, timely scale-up of therapeutics in response to changing market demands.…”

Improving Pharmaceutical Protein Production in Oryza sativa

“…In addition, by utilizing a signal peptide, recombinant proteins produced will be secreted out of the cell into the culture medium, removing the need to extract the protein through cell lysis [25]. Rice has been successfully used to produce human serum albumin, vaccine, antibodies, cytokines, and other pharmaceutical proteins [26]. The characteristics, functions, and yields of protein successfully produced using rice expression systems are summarized (Table 1).…”