Plant-Based Protein Biomanufacturing

Strategies to Increase Heterologous Protein Expression in Rice Grains

“…For stable expression, inheritance of transformed gene(s) over the generations and original copy number might play the key role for overexpressing lines (Nandi and Huang 2009, Figs. 12.3 and 12.4;Broz et al 2013, Fig. 2B).…”

“…The protein composition of the endosperm is 60-70 % glutelins, 25-30 % prolamins, 5-10 % globulins (Glbs), and 0-5 % other proteins, depending on the rice variety. Protein yields have received considerable attention as they play a key role in the performance of the production platform (Zhang et al 2010;Broz et al 2013). The most common strategies to achieve a higher yield of the recombinant protein in rice seeds are by optimizing the promoter region, the untranslated regions, translation efficiency, subcellular localization/targeting of the target protein, codon optimization, knockdown or antisense technology, stable integration of the gene and its copy number, screening, selection, and breeding.…”

“…A scientific study using a discrete event modeling (DEM) approach reported that the projected cost of purified recombinant lactoferrin from rice seeds was US$ 5.90 per g (Nandi et al 2005). It has been reported recently that cost of goods for similar cGMP grade products can be comfortably achieved at US$ 3.75 per g (Broz et al 2013). This validated the idea that incorporating a linearly scalable protein purification methodology into the manufacturing process will have a major impact later in process economics, as long as the procedure allows for linear scalability of each step.…”

“…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.…”

“…Utilizing plants for the large-scale production of recombinant proteins is estimated to be 2-10 % the cost of using microbial platforms, and up to 1000-fold more cost-effective than mammalian platforms (Twyman et al 2003;Sharma and Sharma 2009). Production of heterologous proteins in plant cells is becoming commercially acceptable for human therapeutics (Langer 2010), vaccine antigens (Hefferon 2013), industrial enzymes (Broz et al 2013), and nutraceuticals (Maxmen 2012). The seed has emerged as one of the most prominent plant organs for the recombinant protein production.…”