The Use of Microbial Genetics in the Treatment of Infectious Diseases

The discovery that microorganisms can indeed produce sexually (important for gene mixing from different organisms) by Joshua Lederberg in 1947 who demonstrated the exchange of genetic factors in Escherichia coli (a process of DNA transfer called conjugation) was a major turning point in microbial genetics and led to the use of bacteria as an archetype in genealogical analysis. Some other means in which foreign genes can be transferred into a new cell includes transfection (transformation) and transduction. These processes have proved useful in the management of infectious diseases caused by microorganisms. In this essay, transfection would be used to analyze how microbial genetics are useful in managing infectious diseases.

What is Microbial Genetics and Transfection Procedure?

It is concerned with the study of genes and the expression systems found in microorganisms. Bacterial and viral genetics are branches under microbial genetics. The center of cloning technology is bacterial genetics. Bacteria and viruses are used as agents that carry altered genetic materials into an organism in DNA technology. Genomics dominates genetic research and it involves sequencing of the DNA of genomes. Genomics is the study of the complete structure and function of the whole genome; it has uncovered some genes that can interact to produce desired biological effects in which the researcher is interested in.

Transfection is a procedure in which foreign nucleic acids are introduced into cells to produce genetically modified cells. The genetic material introduced into the cell is either DNA or RNA and can be either stable or transient depending on the nature of the genetic material. There are three methods in which transfection can be carried out and they include biological, physical and chemical methods. A good transfection method would have a high efficiency, low cell toxicity, a little effect on normal physiology, easy to use and should be reproducible. Some bacteria exhibits competence, which is a state in which cells can take up free DNA that are released by other bacteria. Transfection aids in studying gene functions and products by either enhancing or inhibiting specific gene expressions in cells and to produce recombinant proteins in mammalian cells. An example in gene therapy is when a gene of interest is delivered into cells to cure a disease or to improve symptoms as in the case of messenger RNA vaccines. The first evidence of transfection in bacteria was obtained by Fred Griffith (in the late 1920s) while he was working with Streptococcus pneumoniae. In the 1930s at the Rockefeller institute in New York, this process was later explained by Oswald Avery and his associates.

Transfection of Messenger RNAs and Its Deliver

In vitro transcribed messenger RNA is synthetic and is made to resemble natural messenger RNAs. They can be used for protein substitution and to produce vaccines for infectious diseases. In messenger RNA transfection, the messenger RNA is not required to cross the nuclear membrane because it is directly delivered to the cytoplasm and is also expressed there. Once the messenger RNA has been delivered to the cytoplasm, it is immediately translated into a protein. The advantages of messenger RNA transfection are due to the fact that it does not need to be located in a nucleus for it to be expressed thus making it perfect for the transfection of lymphoma, stem cells neurons and other cells which are usually hard to transfect. With messenger RNA transfection cells cannot be overexpressed, this is because any number of messenger RNAs can be introduced into a cell. Other advantages of messenger RNA transfection includes that; there’s no risk of insertional mutagenesis and therefore the genome of the transfected cell is not modified, it is perfect for non-dividing cells because it does not enter the nucleus, when the messenger RNA concentration is changed then the protein expression can be adjusted easily.

A very useful application of messenger RNA transfection is in the production of messenger RNA vaccines. Conventional non messenger RNA vaccines use an inactivated pathogen to protect one against a disease from the pathogen and so tend to produce an adverse reaction but this is not the case with messenger RNA vaccines since it does not involve the use of the pathogens and cannot replicate inside the body, they are not infectious and so there is usually no potential risk of infection, it is also more stable and highly translatable. Messenger RNA vaccines use in vivo transcription, this makes production easier, saves time and economic costs, as well as enabling it to avoid protein and virus derived contamination. Since messenger RNA vaccines involve the transcription of RNA which is transient in nature, it is therefore easily decomposed by physiological metabolic pathways, thus, it will not be a problem for the host to maintain its normal physiological balance.

A functional messenger RNA is one that enters the patient’s cytoplasm and expresses specific antigens. For a drug to pass the cell membrane by free diffusion , it needs to be positively charged because the cell membrane is negatively charged, but messenger RNA is negatively charged and this poses a problem, another problem that messenger RNA encounters is that it is easily degraded by ribonucleases which is found extracellularly. Messenger RNA is easily degraded by normal cellular processes and therefore it is usually encapsulated into a liposomal nanoparticle that shields it from negative charges and prevents degradation by nucleases. The first messenger RNA that was enclosed in liposomal nanoparticle during transfection occurred in 1989; this and other studies proved that transcribed messenger RNAs will take genetic information into the cell tissues to create proteins leading to the birth of messenger RNA vaccines. The core field of messenger RNA drug platform is immunotherapy which includes vaccines against infectious diseases, these vaccines has always been the best way to manage infectious diseases by preventing them; some examples include small pox virus and polio virus which has been completely eradicated and almost fully eradicated respectively.

The messenger RNA used in producing the Covid-19 vaccines contains the information that produces spike proteins which covers the surface of the virus. When the messenger RNA is injected into the body, with the aid of a lipid capsule it enters into the body and is released where it meets ribosomes and begins to produce proteins of the pathogen, these proteins are transferred to the cells surfaces where they are recognized as foreign bodies by the immune cells which then produces antibodies that fights and kills the pathogen. The immune system can remember this pathogen and if infected again by that pathogen, it will be able to fight off the disease.

Conclusion

Messenger RNA vaccine has proven useful in the production of covid-19 vaccines as seen in the Pfizer-BioNTech and Moderna who obtained approval for their messenger RNA base Covid-19 vaccines which has been useful in managing the infectious disease (Covid-19). This is evidence that microbial genetics can be used in managing infectious diseases.

References

• Reichmuth, A.M., Oberli, M.A., Jaklenec, A., Langer, R. and Blankschtein, D., 2016. mRNA vaccine delivery using lipid nanoparticles. Therapeutic delivery, 7(5), pp.319-334.
• Sahin, U., Kariko, K. and Tureci, O., 2014. mRNA-based therapeutics- developing a new class of drugs. Nature reviews Drug Discovery, 13(10), pp.759-780.
• Pardi, N., Hogan, M.J., Porter, F.W. and Weissman, D., 2018. Mrna vaccines-a new era in vaccinology. Nature reviews Drug discovery, 17(4), pp.261-279.
• Kowalski, P.S., Rudra, A, Miao L, Anderson DG. Delivering the messenger: advances in technologies for therapeutic mRNA delivery. Molecular Therapy, 27(4), pp.710-728.
• Kim, T.K. and Eberwine, j.H., 2010. Mammalian cell transfection: the present and the future. Analytical and bioanalytical chemistry, 397(8), pp. 3173-3178.