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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. A possible method for changing natural cell production includes boosting or repressing genes that are involved in the
metabolism Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run c ...
of the product. For example, researchers were able to overexpress transporter genes in hamster ovary cells to increase
monoclonal antibody A monoclonal antibody (mAb, more rarely called moAb) is an antibody produced from a cell Lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell. Monoclonal antibodies ...
yield. Another approach could involve incorporating biologically foreign genes into an existing cell line. For example, ''
E.Coli ''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus ''Esche ...
'', which synthesizes ethanol, can be modified using genes from '' Zymomonas mobilis'' to make
ethanol fermentation Ethanol fermentation, also called alcoholic fermentation, is a biological process which converts sugars such as glucose, fructose, and sucrose into cellular energy, producing ethanol and carbon dioxide as by-products. Because yeasts perform this ...
the primary cell fermentation product.


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 Yeasts are eukaryotic, single-celled microorganisms classified as members of the fungus kingdom. The first yeast originated hundreds of millions of years ago, and at least 1,500 species are currently recognized. They are estimated to constit ...
strain which allows the cells to grow on substrate cheaper than the traditional
glucose Glucose is a simple sugar with the molecular formula . Glucose is overall the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, u ...
. 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.


Augmenting cells to produce new products

Closely tied with the field of
biotechnology Biotechnology is the integration of natural sciences and engineering sciences in order to achieve the application of organisms, cells, parts thereof and molecular analogues for products and services. The term ''biotechnology'' was first used ...
, this subject of cell engineering employs
recombinant DNA Recombinant DNA (rDNA) molecules are DNA molecules formed by laboratory methods of genetic recombination (such as molecular cloning) that bring together genetic material from multiple sources, creating sequences that would not otherwise be fo ...
methods to induce cells to construct a desired product such as a
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
,
antibody An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...
, or
enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...
. One of the most notable examples of this subset of cellular engineering is the
transformation Transformation may refer to: Science and mathematics In biology and medicine * Metamorphosis, the biological process of changing physical form after birth or hatching * Malignant transformation, the process of cells becoming cancerous * Tran ...
of '' E. Coli'' to transcript and
translate Translation is the communication of the meaning of a source-language text by means of an equivalent target-language text. The English language draws a terminological distinction (which does not exist in every language) between ''transl ...
a precursor to insulin which drastically reduced the cost of production. 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. Finally, much progress has been made in engineering cells to produce antigens for the purpose of creating
vaccines A vaccine is a biological preparation that provides active acquired immunity to a particular infectious or malignant disease. The safety and effectiveness of vaccines has been widely studied and verified.< ...
.


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. For example, in 1988 one group of researchers from the Illinois Institute of Technology successfully expressed a ''
Vitreoscilla ''Vitreoscilla'' is a genus of Gram-negative aerobic bacterium. The bacterial haemoglobin ( VHb) was first discovered from ''Vitreoscilla'', and VHb is found to have a wide range of biological and biotechnological applications including promoti ...
'' 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.


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. One example of directed stem cell engineering includes partially differentiating stem cells into
myocytes A muscle cell is also known as a myocyte when referring to either a cardiac muscle cell (cardiomyocyte), or a smooth muscle cell as these are both small cells. A skeletal muscle cell is long and threadlike with many nuclei and is called a muscl ...
to enable production of pro-myogenic factors for the treatment of
sarcopenia Sarcopenia is a type of muscle loss ( muscle atrophy) that occurs with aging and/or immobility. It is characterized by the degenerative loss of skeletal muscle mass, quality, and strength. The rate of muscle loss is dependent on exercise level, ...
or muscle disuse atrophy.


History

The phrase "cell engineering" was first used in a published paper in 1968 to describe the process of improving fuel cells. 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. Despite the rising popularity of the phrase, there remains unclear boundaries between cell engineering and other forms of biological engineering.


Examples

* Therapeutic
T cell A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell r ...
engineering: altering T cells to target cancer-related antigens for treatment *
Monoclonal antibody A monoclonal antibody (mAb, more rarely called moAb) is an antibody produced from a cell Lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell. Monoclonal antibodies ...
production: improving monoclonal antibody production using engineered cells * ''In vivo'' cell factories: engineering cells to produce therapeutics within the patient's body * Directed stem cell differentiation: using external factors to direct stem cell differentiation


References

{{reflist


External Links


Institute for Cell Engineering
at Johns Hopkins University School of Medicine
Cell & Tissue Engineering
at University of California, Berkeley Bioengineering Department Cells Cell lines Molecular biology