Optimization of inside and outside factors to improve recombinant protein yield in plant

Abstract

an improvement of critical features, including transcription, translation and post-translational modifications, in plant cells could make plant systems a safe and economical alternative for biopharmaceutical production. Hence, in this review, the most recent advances influencing the upstream and downstream processes involved in recombinant protein accumulation in plant cells are described. We also discuss how plant systems are becoming the benchmark for the production of several biopharmaceuticals.Keywords Heterologous expression · Host systems · Post-translational modifications · Plant-based pharmaceuticals · Recombinant protein identification and characterization of a promising regulatory pathway for the large-scale production of biopharmaceuticals could strongly contribute to the benefits of this system (Fischer et al. 2012). Molecular pharming technology presents several advantages, including (a) the production of low-cost biomass; (b) end-products lacking human toxicity; (c) the accumulation of complex proteins with correct and proper folding; and (d) straightforward methods for protein purification (Moustafa et al. 2015). Furthermore, molecular pharming offers a flexible, scalable and diverse alternative method for producing new, Abstract The use of plant systems as factories for recombinant protein production became a prominent alternative for pharmaceutical industries due to their high potential for protein accumulation. In the last decades, the application of plants for protein production has gained more attention, as plants represent an economic strategy that leads to high levels of purified and active proteins for the pharmaceutical sector. Currently, FDA approval of the first generation of recombinant proteins produced in carrot cells, taliglucerase alfa, demonstrated that plant cells have a significant capacity to express complex proteins for therapeutic use. Although plant systems still have technical and economic barriers that require improvements in future years, the optimization of upstream and downstream components affecting protein accumulation is considered a key feature in the development of new pharmaceutical proteins. Therefore,

Gene-silencing suppressors for high-level production of the HIV-1 entry inhibitor griffithsin in Nicotiana benthamiana

“…Transient gene expression based on agroinfiltration is an efficient, cost-effective and time-saving strategy for obtaining high amounts of recombinant proteins, as stable genetic transformation is a slow process and requires months or years to generate transgenic plants due to regeneration protocols. In addition, transient expression is genome integration-independent strategy, which will not be affected by position effects existing in stable transformation, once that the expression vector remains an episomal DNA molecule [22]. Our result is in accordance with previous works, which indicated that agroinfiltration could efficiently resulted in transferring of Agrobacterium into the plant leaves and robust expression of recombinant proteins [24,[52][53][54].…”

“…Using this system, the need for plasmid delivery based on complicated methods of generating RNA is eliminated. The MagnICON system provides an efficient system without functional infectious proteins because of the deletion of the CP gene, whereas the yield and speed of viral system are maintained [22].…”

Efficient Plant Production of Recombinant NS1 Protein for Diagnosis of Dengue

“…The yield obtained in this work, 203 mg of NS1DENV2 per kilogram of fresh leaf, showed that the plant expression system used was efficient and consistent with other systems aimed at optimizing the production of recombinant protein, which obtained, respectively, 70 mg/kg and 24.5 mg/kg (Fedosov et al, 2003;Rigano et al, 2004;Yang et al, 2015;Habibi et al, 2017;Okay and Sezgin, 2018). In their work, Jeong et al (2018) demonstrated that it is possible to achieve overexpression of the mCherry protein (0.4 mg) per g of Arabidopsis callus.…”

The potential of plant systems to break the HIV‐TB link

“…Plant secondary metabolites are involved in the adaptation of plants to their environment, and most of these metabolites are involved in plant defence mechanisms against pathogen invasion and abiotic stress (Habibi et al ., 2017b). These valuable compounds could be extracted from different parts of plants, such as leaves, shoots, roots and flowers, and investigated for their potential as anti‐HIV and anti‐TB drugs.…”

“…Expression systems also have been developed based on other plants such as rice, carrot, maize, Spinach, lettuce (Chan and Daniell, 2015;Lakshmi et al,2013), cowpea, potato, Arabidopsis (Scotti et al, 2010) and moss (Orellana-Escobedo et al, 2015) for the production of recombinant HIV and TB antigens. Advantages and disadvantages of these systems are reviewed elsewhere by Habibi et al (2017b).…”