The application of recombinant proteins has saved millions of patients’ lives – and still counting. Entire industries have been built around the research and production of recombinant proteins in the past few decades. Since the COVID-19 pandemic everybody knows that they are ubiquitous in diagnostic medicine in the form of test kits and assays. Moreover, they constitute essential pharmaceutical therapies.
In this article we want to give answers to these questions: What are recombinant proteins and how are they used?
Recombinant proteins and their encoding recombinant DNA were at first an idea brought up by graduate student Peter Lobban who studied under Prof. Kaiser at Stanford University Medical School. In 1972, the first reports of successful experiments appeared, and in 1980, Paul Berg received a Nobel Prize for work being done on recombinant biomolecules.
The key concept is the introduction of foreign genetic material into the biochemical machinery of host organisms (recombination of genetic fragments) such as Escherichia coli (E. coli) to reprogram their protein expression to produce a desired (recombinant) peptide or protein of interest.
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Soon thereafter, recombinant technology was used to produce recombinant proteins as recombinant human insulin, thus proving the major impact and economic potential of these developments.
Nowadays, a multi-billion dollar market for biopharmaceuticals surrounds the biotechnology of recombinant protein expression that was built around recombinant technology.
After establishing the origins of recombinant proteins, we want to dive deeper into the topic and highlight three major fields of applications for recombinant human proteins.
Recombinant proteins are indispensable tools in research. Typical fields range from cell biology, pharmacology, medicine and biochemistry, to molecular biology and many more. They are used for in vitro, as well as in vivo study designs. They are used in popular techniques like Western Blots or ELISA which are essential in the life sciences. Another example is the directed mutation of receptor proteins to study mechanisms of action of inhibitors in drug discovery.1
Aside from research applications, recombinant proteins are commonly used in the diagnostic branch of medicine in assays and as therapeutic proteins, especially monoclonal antibodies with pathogenic antigens, as replacement therapies for hormonally active substances such as growth factors and insulin, and as adjuvant therapies for infectious diseases, e.g. interferons to treat hepatitis.
In all applications which involve the administration of recombinant proteins into patients, great care has to be taken to ensure high-quality target proteins from mammalian cells such as CHO cells. Prokaryotic expression systems or unsuitable cell lines lead to faulty post-translational modifications such as glycosylation patterns and cause immunogenicity and severe side effects, even though the DNA sequence itself underwent optimization. The FDA ensures the use of appropriate eukaryotic cell culture, suitable expression vectors, sufficient protein purification and calls for in depth characterization of the products.
The onset of recombinant technology was game-changing for biotechnology. Prior to the development of cloning plasmids and engineering the genome of host cells, biotechnology had to rely on the search and isolation of microorganisms from the environment capable of producing desirable small molecules (e.g. penicillins). Most of these findings were due to sheer luck.
The directed production of recombinant proteins really changed the entire field, because now it was possible to develop and optimize synthetic fusion proteins at the nucleic acid level using novel reagents and enzymes, incorporate promoter regions into the DNA to ensure high levels of RNA transcription and resulting in high yields of protein synthesis from amino acids.
There are manifolds of studies going on that are expected to yield ground-breaking results and novel applications for recombinant proteins:
Recombinant proteins offer so many opportunities to further medicine and help mankind become healthier. It will be exciting to witness how these and the following applications of recombinant proteins will unfold in the future.
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