Biology:Cell engineering

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Cells engineered to fluoresce under UV light.

Cell engineering is the purposeful process of adding, deleting, or modifying genetic sequences in living cells to achieve biological engineering goals such as altering cell production, changing cell growth and proliferation requirements, adding or removing cell functions, and many more. Cell engineering often makes use of DNA technology to achieve these modifications as well as closely related tissue engineering methods. Cell engineering can be characterized as an intermediary level in the increasingly specific disciplines of biological engineering which includes organ engineering, tissue engineering, protein engineering, and genetic engineering.

The field of cellular engineering is gaining more traction as biomedical research advances in tissue engineering and becomes more specific. Publications in the field have gone from several thousand in the early 2000s to nearly 40,000 in 2020.

Overview

Improving production of natural cellular products

One general form of cell engineering involves altering natural cell production to achieve a more desirable yield or shorter production time.[1] A possible method for changing natural cell production includes boosting or repressing genes that are involved in the metabolism of the product. For example, researchers were able to overexpress transporter genes in hamster ovary cells to increase monoclonal antibody yield.[2] Another approach could involve incorporating biologically foreign genes into an existing cell line. For example, E.Coli, which synthesizes ethanol, can be modified using genes from Zymomonas mobilis to make ethanol fermentation the primary cell fermentation product.[3]

Altering cell requirements

Another beneficial cell modification is the adjustment of substrate and growth requirements of a cell. By changing cell needs, the raw material cost, equipment expenses, and skill required to grow and maintain cell cultures can be significantly reduced. For example, scientists have used foreign enzymes to engineer a common industrial yeast strain which allows the cells to grow on substrate cheaper than the traditional glucose.[4] Because of the biological engineering focus on improving scale-up costs, research in this area is largely focused on the ability of various enzymes to metabolize low-cost substrates.[5]

Augmenting cells to produce new products

Closely tied with the field of biotechnology, this subject of cell engineering employs recombinant DNA methods to induce cells to construct a desired product such as a protein, antibody, or enzyme. One of the most notable examples of this subset of cellular engineering is the transformation of E. Coli to transcript and translate a precursor to insulin which drastically reduced the cost of production.[6] Similar research was conducted shortly after in 1979 in which E. Coli was transformed to express human growth hormone for use in treatment of pituitary dwarfism.[7] Finally, much progress has been made in engineering cells to produce antigens for the purpose of creating vaccines.[8]

Adjustment of cell properties

Within the focus of bioengineering, various cell modification methods are utilized to alter inherent properties of cells such as growth density, growth rate, growth yield, temperature resistance, freezing tolerance, chemical sensitivity, and vulnerability to pathogens.[1] For example, in 1988 one group of researchers from the Illinois Institute of Technology successfully expressed a Vitreoscilla hemoglobin gene in E. Coli to create a strain that was more tolerant to low-oxygen conditions such as those found in high density industrial bioreactors.[9]

Stem cell engineering

One distinct section of cell engineering involves the alteration and tuning of stem cells. Much of the recent research on stem cell therapies and treatments falls under the aforementioned cell engineering methods. Stem cells are unique in that they may differentiate into various other types of cells which may then be altered to produce novel therapeutics or provide a foundation for further cell engineering efforts.[10] One example of directed stem cell engineering includes partially differentiating stem cells into myocytes to enable production of pro-myogenic factors for the treatment of sarcopenia or muscle disuse atrophy.[11]

History

The phrase "cell engineering" was first used in a published paper in 1968 to describe the process of improving fuel cells.[12] The term was then adopted by other papers until the more specific "fuel-cell engineering" was used.

The first use of the term in a biological context was in 1971 in a paper which describes methods to graft reproductive caps between algae cells.[13] Despite the rising popularity of the phrase, there remains unclear boundaries between cell engineering and other forms of biological engineering.[1]

Examples

  • Therapeutic T cell engineering:[14] altering T cells to target cancer-related antigens for treatment
  • Monoclonal antibody production:[15] improving monoclonal antibody production using engineered cells
  • In vivo cell factories:[16] engineering cells to produce therapeutics within the patient's body
  • Directed stem cell differentiation:[17] using external factors to direct stem cell differentiation
  • Antibody Drug Conjugates[18]: engineering antibody and cytotoxic drug linkages for disease treatment

References

  1. ↑ 1.0 1.1 1.2 Cameron, Douglas C.; Tong, I-Teh (1993-01-01). "Cellular and metabolic engineering" (in en). Applied Biochemistry and Biotechnology 38 (1): 105–140. doi:10.1007/BF02916416. ISSN 1559-0291. PMID 8346901. https://doi.org/10.1007/BF02916416. 
  2. ↑ Tabuchi, Hisahiro; Sugiyama, Tomoya; Tanaka, Saeko; Tainaka, Satoshi (2010). "Overexpression of taurine transporter in Chinese hamster ovary cells can enhance cell viability and product yield, while promoting glutamine consumption" (in en). Biotechnology and Bioengineering 107 (6): 998–1003. doi:10.1002/bit.22880. ISSN 1097-0290. PMID 20661907. https://onlinelibrary.wiley.com/doi/abs/10.1002/bit.22880. 
  3. ↑ Ingram, L O; Conway, T; Clark, D P; Sewell, G W; Preston, J F (1987-10-01). "Genetic engineering of ethanol production in Escherichia coli". Applied and Environmental Microbiology 53 (10): 2420–2425. doi:10.1128/aem.53.10.2420-2425.1987. PMID 3322191. Bibcode: 1987ApEnM..53.2420I. 
  4. ↑ Ledesma-Amaro, Rodrigo; Nicaud, Jean-Marc (October 2016). "Metabolic Engineering for Expanding the Substrate Range of Yarrowia lipolytica". Trends in Biotechnology 34 (10): 798–809. doi:10.1016/j.tibtech.2016.04.010. ISSN 0167-7799. PMID 27207225. https://doi.org/10.1016/j.tibtech.2016.04.010. 
  5. ↑ Prieto, M A; Perez-Aranda, A; Garcia, J L (1993-04-01). "Characterization of an Escherichia coli aromatic hydroxylase with a broad substrate range". Journal of Bacteriology 175 (7): 2162–2167. doi:10.1128/jb.175.7.2162-2167.1993. PMID 8458860. 
  6. ↑ Goeddel, D. V.; Kleid, D. G.; Bolivar, F.; Heyneker, H. L.; Yansura, D. G.; Crea, R.; Hirose, T.; Kraszewski, A. et al. (1979-01-01). "Expression in Escherichia coli of chemically synthesized genes for human insulin" (in en). Proceedings of the National Academy of Sciences 76 (1): 106–110. doi:10.1073/pnas.76.1.106. ISSN 0027-8424. PMID 85300. Bibcode: 1979PNAS...76..106G. 
  7. ↑ Goeddel, David V.; Heyneker, Herbert L.; Hozumi, Toyohara; Arentzen, Rene; Itakura, Keiichi; Yansura, Daniel G.; Ross, Michael J.; Miozzari, Giuseppe et al. (October 1979). "Direct expression in Escherichia coli of a DNA sequence coding for human growth hormone" (in en). Nature 281 (5732): 544–548. doi:10.1038/281544a0. ISSN 1476-4687. PMID 386136. Bibcode: 1979Natur.281..544G. https://www.nature.com/articles/281544a0. 
  8. ↑ Nascimento, I. P.; Leite, L. C. C. (December 2012). "Recombinant vaccines and the development of new vaccine strategies" (in en). Brazilian Journal of Medical and Biological Research 45 (12): 1102–1111. doi:10.1590/S0100-879X2012007500142. ISSN 0100-879X. PMID 22948379. 
  9. ↑ Dikshit, Kanak L.; Webster, Dale A. (1988-10-30). "Cloning, characterization and expression of the bacterial globin gene from Vitreoscilla in Escherichia coli" (in en). Gene 70 (2): 377–386. doi:10.1016/0378-1119(88)90209-0. ISSN 0378-1119. PMID 2850971. https://dx.doi.org/10.1016/0378-1119%2888%2990209-0. 
  10. ↑ Li, Shengwen Calvin; Wang, Lang; Jiang, Hong; Acevedo, Julyana; Chang, Anthony Christopher; Loudon, William Gunter (2009-03-01). "Stem cell engineering for treatment of heart diseases: Potentials and challenges" (in en). Cell Biology International 33 (3): 255–267. doi:10.1016/j.cellbi.2008.11.009. ISSN 1065-6995. PMID 19084605. 
  11. ↑ Fix, Dennis K.; Mahmassani, Ziad S.; Petrocelli, Jonathan J.; de Hart, Naomi M.M.P.; Ferrara, Patrick J.; Painter, Jessie S.; Nistor, Gabriel; Lane, Thomas E. et al. (2021-12-01). "Reversal of deficits in aged skeletal muscle during disuse and recovery in response to treatment with a secrotome product derived from partially differentiated human pluripotent stem cells" (in en). GeroScience 43 (6): 2635–2652. doi:10.1007/s11357-021-00423-0. ISSN 2509-2723. PMID 34427856. PMC 8602548. https://doi.org/10.1007/s11357-021-00423-0. 
  12. ↑ Thurber, W. C. (1968-05-01). "Closure to "Discussions of 'A Fuel Cell Power Plant for a Deep Diving Submarine'" (1968, ASME J. Eng. Ind., 90, pp. 266–267)". Journal of Engineering for Industry 90 (2): 267. doi:10.1115/1.3604626. ISSN 0022-0817. 
  13. ↑ Bonotto, S.; Kirchmann, R.; Manil, P. (1971-01-01). "Cell Engineering in Acetabularia: A Graft Method for Obtaining Large Cells with Two or More Reproductive Caps". Giornale Botanico Italiano 105 (1): 1–9. doi:10.1080/11263507109431460. ISSN 0017-0070. https://doi.org/10.1080/11263507109431460. 
  14. ↑ Sadelain, Michel; Rivière, Isabelle; Riddell, Stanley (May 2017). "Therapeutic T cell engineering" (in en). Nature 545 (7655): 423–431. doi:10.1038/nature22395. ISSN 1476-4687. PMID 28541315. Bibcode: 2017Natur.545..423S. 
  15. ↑ Rita Costa, A.; Elisa Rodrigues, M.; Henriques, Mariana; Azeredo, Joana; Oliveira, Rosário (2010-02-01). "Guidelines to cell engineering for monoclonal antibody production" (in en). European Journal of Pharmaceutics and Biopharmaceutics 74 (2): 127–138. doi:10.1016/j.ejpb.2009.10.002. ISSN 0939-6411. PMID 19853660. https://www.sciencedirect.com/science/article/pii/S0939641109003166. 
  16. ↑ Mansouri, Maysam; Fussenegger, Martin (2021-09-29). "Therapeutic cell engineering: designing programmable synthetic genetic circuits in mammalian cells" (in en). Protein & Cell 13 (7): 476–489. doi:10.1007/s13238-021-00876-1. ISSN 1674-8018. PMID 34586617. 
  17. ↑ Clause, Kelly C.; Liu, Li J.; Tobita, Kimimasa (April 2010). "Directed Stem Cell Differentiation: The Role of Physical Forces" (in en). Cell Communication & Adhesion 17 (2): 48–54. doi:10.3109/15419061.2010.492535. ISSN 1541-9061. PMID 20560867. 
  18. ↑ Pettinato, Mark C. (2021-10-27). "Introduction to Antibody-Drug Conjugates". Antibodies 10 (4): 42. doi:10.3390/antib10040042. ISSN 2073-4468. PMID 34842621. 

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