Recent Developments of Recombinant Protein Expression for Therapeutic Purposes
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In the past few years, the use of therapeutic recombinant proteins has rapidly expanded in the field of biotechnology. There has been a significant development in the application of the mammalian expression system for recombinant protein production which allows high gene expression, resulting in the better quality and quantity of the expressed product [1]. Chinese hamster ovary cells, murine myeloma lymphoblstoid like cells, human embryonic kidney cells, and baby hamster kidney cells have been used successfully to produce multiple pharmaceutical products [2]. Mammalian expression system improves the proper glycosylation of recombinant proteins which are very helpful in product folding, post-translational modifications, assembly and increasing solubility [3-6].
Meanwhile, in prokaryotic expression system, E. coli is widely used because it is easy to handle, multiplies rapidly, produces clones, and remains cost effective in large scale production [7]. Recently, these expression systems have been used for antibody fragment productions and their proper folding with co-expression of chaperones [8]. Moreover, E. coli has been used for the production of cancer cell penetrating peptides which warrant the targeted delivery of drugs to specific effector cells only (add reference).
Yeast systems are also currently used for antibody fragment production and the large scale production of insulin. The application of cell free expression systems allows the production of toxic proteins as there is no need to maintain cell viability [9, 10].
The purification and optimization of recombinant proteins has always been challenging for scientists who strive to increase the overall yield of the product. Many affinity chromatography techniques have been introduced for the efficient purification of the protein of interest [11].
Despite extensive research and the development of new methodologies to produce and purify the recombinant therapeutic proteins, there are still hurdles and challenges with all expression systems. E. coli produces inclusion bodies and many mammalian cell types do not show the same results with the same recombinant protein [12]. So, appropriate features should be added to the expression systems to better improvise the recovery, production and purification of recombinant proteins.
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References
Khan KH. Gene expression in Mammalian cells and its applications. Adv Pharm Bull. 2013;3(2):257-263. https://doi.org/10.5681/apb.2013.042
Zhu J. Mammalian cell protein expression for biopharmaceutical production. Biotechnol Adv. 2012;30(5):1158-1170. https://doi.org/10.1016/j.biotechadv.2011.08.022
Missoum A. Recombinant Protein Production and Purification Using Eukaryotic Cell Factories. Methods Mol Biol. 2021;2290:215-228. https://doi.org/10.1007/978-1-0716-1323-8_15
Pu H, Cashion LM, Kretschmer PJ, Liu Z. Rapid establishment of high-producing cell lines using dicistronic vectors with glutamine synthetase as the selection marker. Mol Biotechnol. 1998;10(1):17-25. https://doi.org/10.1007/BF02745860
Mielke C, Tümmler M, Schübeler D, von Hoegen I, Hauser H. Stabilized, long-term expression of heterodimeric proteins from tricistronic mRNA. Gene. 2000;254(1-2):1-8.
Hennecke M, Kwissa M, Metzger K, et al. Composition and arrangement of genes define the strength of IRES-driven translation in bicistronic mRNAs. Nucleic Acids Res. 2001;29(16):3327-3334. https://doi.org/10.1093/nar/29.16.3327
Swartz JR. Advances in Escherichia coli production of therapeutic proteins. Curr Opin Biotechnol. 2001;12(2):195-201. https://doi.org/10.1016/s0958-1669(00)00199
Huang J, Zhao Q, Chen L, et al. Improved production of recombinant Rhizomucor miehei lipase by coexpressing protein folding chaperones in Pichia pastoris, which triggered ER stress. Bioengineered. 2020;11(1):375-385. https://doi.org/10.1080/21655979.2020
Tripathi NK, Shrivastava A. Recent Developments in Bioprocessing of Recombinant Proteins: Expression Hosts and Process Development. Front Bioeng Biotechnol. 2019;7:420. Published 2019. https://doi.org/10.3389/fbioe.2019.00420
Huang J, Yang Z, Zhu R, et al. Efficient heterologous expression of an alkaline lipase and its application in hydrolytic production of free astaxanthin. Biotechnol Biofuels. 2018;11:181. Published 2018. https://doi.org/10.1186/s13068-018-1180-2
Huang J, Wang Q, Bu W, et al. Different construction strategies affected on the physiology of Pichia pastoris strains highly expressed lipase by transcriptional analysis of key genes. Bioengineered. 2019;10(1):150-161. https://doi.org/10.1080/21655979.2019.1614422
Kim K, Choe D, Lee DH, Cho BK. Engineering Biology to Construct Microbial Chassis for the Production of Difficult-to-Express Proteins. Int J Mol Sci. 2020;21(3):990. Published 2020. https://doi.org/10.3390/ijms21030990
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