Transgenesis and medicine

The process of obtaining animals with modified genotypes (transgenic animals) for the needs of modern medicine is used in many aspects.

People's life expectancy is increasing, which is why the number of patients with chronic diseases is increasing. Civilization diseases, such as diabetes, arterial hypertension, coronary artery disease, obesity or cancer cause dysfunction of vital organs - the heart, kidneys, lungs, pancreas and liver. Pharmacological treatment of the effects of civilization diseases, despite enormous progress in the development of new, more effective pharmaceuticals, is in many cases insufficient. The only salvation in such situations is to carry out a transplant of the appropriate organ. Transplantology allows transplantation of virtually any organ. The main limitation of its use is the availability of human organs suitable for transplantation. The growing demand for human organs useful for transplants means that alternative sources are sought that will be able to meet the growing needs. Xenotransplantation - a procedure for transplanting, implanting or infusing cells, tissues, organs or fluids from other organisms (usually animals) into the human body. The first attempts at xenotransplantation were carried out in the 1th century [60]. In the 80s, many attempts were made to transplant tissues and organs from animals, but they were unsuccessful. The development of the basics of genetic engineering in the 2s, enabling genetic modification of genotypes, opened up virtually unlimited possibilities for the use of xenotransplantation. A number of studies have shown that the organism that best meets the criteria for organ usefulness for xenotransplantation is the domestic pig. The size of pig's organs, their physiological efficiency is almost identical to that of humans. Moreover, the pig is a fertile and fertile species, and easy and cheap to maintain. It grows quickly, thanks to which its organs reach full efficiency very quickly. It is also a species with a complete genome map. This makes the domestic pig a prime focus of work to modify its genome to obtain organs for xenotransplantation. The most spectacular example is keeping a baboon alive, which has survived several months with a heart transplanted from a transgenic pig [3]. Until now, this period had not exceeded one month. This achievement allows for the conclusion that in the near future, transgenic pigs will be tissue and organ banks for xenotransplantation. It should be noted that transgenic pigs are already used as donors of valves, modified Langerhans islets or skin used as bio-dressings in the treatment of extensive burns in humans [XNUMX].

In order to meet the challenges faced by modern medicine, it is necessary to conduct research that will allow us to understand the etiology of specific disease entities, to trace the process of its course and on this basis to develop an effective therapy or prophylaxis. For ethical reasons, research of this type on the human body is unacceptable and impossible. Progress in biological sciences, especially in genetic engineering, which now allows any modification of DNA or RNA and the study of many processes taking place in cells at the molecular and sub-molecular level, has allowed modern medicine to use a number of tools that allow for in-depth and precise tracking of disease processes and and developing effective therapies. Experimental animals play an invaluable role in research in regenerative and translational medicine. Currently, experimental model animals can be obtained by modifying genotypes directed towards a specific research goal (e.g. induction of a specific human disease entity - diabetes, ischemic coronary disease, skin cancer, Alzheimer's disease). Understanding the human genome and creating its maps, understanding the genomes of laboratory animals (mice, rats) and farm animals - pig, sheep, rabbit, made it possible to determine phylogenetic similarities and differences in the expression of specific genes. This enables the selection and creation of transgenic animal models that most adequately reflect the etiology and course of a specific human disease [4].

Modifications of the genomes of animals (transgenesis) are also carried out in order to obtain proteins of therapeutic importance. The comparison of various bioreactor systems currently used to produce proteins of therapeutic importance (systems based on genetically modified bacteria, insect cells, plants or animals) clearly showed that transgenic animals whose genotype was modified so that they produced specific therapeutic proteins in their mammary glands or body fluids , are the most efficient bioreactors. Transgenic live bioreactors produce proteins in large amounts, the synthetic analogs of which are ineffective, expensive or impossible to synthesize. Examples of such live bioreactors are animals that, for example, in milk produce blood coagulation factors, plasminogen activator, growth hormone, lactoferrin, insulin and many other biologically active proteins [5].

Advances in genetic engineering and the challenges faced by medicine are intertwining and driving each other. Both areas have a stimulating effect on each other - one of them offers newer, more sophisticated tools enabling work on genomes (transgenesis), the other one uses these possibilities in creating models, therapies and processes saving human life.


Źródła:

  • [1] - Smorąg, R. Słomski, L. Cierpka - Biotechnological and medical basis of xenotransplantation. Ed. II. Poznań Publishing House. ISBN 83-7712-1122.
  • [2] - Listen: Pig-heart transplants in baboons work for longer than ever before, www.nature.com.
  • [3] - Bottino and M. Trucco - Use of genetically-engineered pig donors in islet transplantation, World J Transplant. 2015 Dec 24; 5 (4): 243 – 250.
  • [4] - Dziegiel, P. Szczurek, J. Jura, M. Pieszka - Pig as a model animal in biomedical translational research. Progress Hig Med Dosw 2018; 72: 1032-1042.
  • [5] - Wang, S Zhao, L Bai, J. Fan, E. Liu - Review Article. Expression Systems and Species Used for Transgenic Animal Bioreactors. BioMed Research International Volume 2013, Article ID 580463, 9 pages http://dx.doi.org/10.1155/2013/580463

Author: Jacek Jura

The article was prepared as part of the ProBio Małopolska project

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