Gene therapy has
progressed significantly in recent years. However, issues surrounding its use
are controversial. Present and evaluate the arguments for and against the use
of gene therapy in humans.

Nowadays, gene therapy has a significant impact on our life. It is widely used, even if we do not realize it. This field of science is currently growing, so it is worth it is worth to know something about it. Gene therapy is a method of treatment of diseases with a genetic basis. Its aim is to eliminate abnormal cells, introduce changes in the phenotype and physiology of cells, as well as, among other things, introduce into the cell the correct copy of the gene. According to U.S National Library of Medicine (2018), gene therapy is a therapy in which genes are used to treat or prevent the different diseases. Thanks to this technique, it is possible that in the future doctors instead of administering drugs to patients or surgeries, will heal people by inserting appropriate genes into their cells. There are different methods in gene therapy, such as: “replacing a mutated gene that causes disease with a healthy copy of the gene; inactivating, or “knocking out,” a mutated gene that is functioning improperly; introducing a new gene into the body to help fight a disease”. Gene therapy is quite new, it is constantly being researched in terms of whether it is safe and what it can have in the future. Although it is not fully researched, it seems to be a very promising technique, it can be a huge opportunity to discover ways to treat various diseases, including hereditary diseases, certain types of cancer and some viral infections). In this work, arguments for and against the use of gene therapy in humans will be discussed. Introducing therapeutic nucleic acids into the cells of the human body, i.e. gene therapy, has the potential to revolutionize modern medicine but recent years have brought this field both many successes and failures.

The removal of undesirable effects on the organism caused
by erroneous gene mutations by introducing foreign, but correct DNA or RNA
sequences into the body cells, is gene therapy. This is a very modern method of
treatment that can be performed by administering a preparation containing a
complete gene or only selected DNA or RNA fragments. We can divide gene therapy
into two categories: germ line gene therapy and somatic gene therapy. In
somatic gene therapy genetic the change is not passed along to the next
generation, although the gene material is inserted into a cell. In germ line
therapy gene the change is heritable so gene will be passed on to the next
generation. (Wirth, Parker and Ylä-Herttuala, 2013) British law prohibits editing of germ-cells or embryos in a clinical
context. At present it is unlikely to this process be allowed in any European
jurisdiction. (Wellcome.ac.uk, 2018)

There has been considerable success using gene therapy in the treatment of genetic diseases associated with immunodeficiency. Very good results are also obtained in the treatment of hemophilia, where a significant improvement in patients’ condition is achieved. In the case of Parkinson’s disease, the use of therapy contributes to the improvement of motor function, but does not completely relieve the disease symptoms.
There is great hope in cancer gene therapy because it does not require a long-lasting process of reading and copying the correct genetic information to the cells. The challenge is to fight congenital genetic diseases, which, as in the case of cancer, require a longer process of reading and copying the therapeutic genetic code, which often causes side effects that threaten the patient’s life.

In recent years, there have been many studies testing gene therapy in other
disease entities. According to Nathwani et al., (2014) an
example is hemophilia B – a genetic disorder that is deficient in blood
coagulation factor IX. It manifests itself in numerous, frequent bleeding and
requires constant exogenous supply of missing protein to the blood of patients.
Monogenic diseases such as hemophilia are an ideal target for gene therapy,
which is why scholars sought to heal patients by providing the correct form of
the gene encoding factor IX using a specially crafted adenoviral vector. The
results of this study were very encouraging. Stable expression of factor IX at
the level of 3 to 11% of the norm was obtained, which was enough to alleviate
the symptoms of the disease. Over a few to over a dozen months of follow-up, 4
of 6 patients did not observe any bleeding, while the other two reduced the
need for frequent prophylactic injections. Side effects were very light. They
mainly concerned the increase in the level of liver enzymes.

According to Coune, Schneider and Aebischer (2012)
another example of recent advances in gene therapy is the attempt to improve
the status of patients with advanced stage of Parkinson’s disease. The recently
completed clinical trial using the lentiviral vector attempted to restore the
proper production of dopamine in certain brain centers (the deficiency of this
neurotransmitter underlies the disease). The vector contained three genes
encoding key enzymes for dopamine synthesis, which, expressed in the
corresponding neurons, were able to repair the biochemical defect present in
patients with Parkinson’s syndrome. As a result of the innovative therapy, 15
patients experienced significant improvement in motor function with minimal
side effects. Although scientists have not observed complete remission of the
disease, this trial provides a solid basis for further research.

According to Medicalnewstoday.com, (2018) Cellular Networking, Integration
and Processing – is a gene transfer technique, which “involves introducing
specific genes into the pancreas using a virus as a vector”.” The team notes
that beta cells are rejected in patients with type 1 diabetes. With the gene
transfer method, the newly introduced genes encourage non-beta cells to produce
insulin, without any side effects.”

However, many failures put a shadow on successful gene therapy. According to Wong, Hawthorne and Manolios (2010) gene therapy can be very helpful in the fight against diabetes but also carries a lot of risks. Gene therapy must be refined, because uncontrolled distribution of genes and cells in the body can be very dangerous. It could lead to a situation in which all cells would start to produce insulin, and then our body would be flooded with it. Only pancreatic cells are now created for the production of insulin. A well-functioning pancreas controls the level of this hormone. Too high a level of insulin would lead to hypoglycemic shock, which is life-threatening. They are especially frequent when adenoviral vectors are used because a significant part of the population has antibodies directed against them (adenoviruses are known human pathogens, they cause colds, among others).

According to (Sibbald, 2018)  and NATURE International weekly journal of science (2016) in
september 1999, 18-year-old Jesse Gelsinger took part in a clinical trial
testing gene therapy in a genetic condition called ornithine
carbamyltransferase deficiency. This enzyme is indispensable for a man to
properly metabolize and excrete nitrogen from the breakdown of proteins. The
accumulating toxic ammonia causes progressive damage to the central nervous
system ending in a coma. The case of Jesse was so light that the symptoms of
the disease could be controlled by diet and medications. As part of the study,
he received the highest dose of the viral vector. The next morning, Jesse
showed symptoms of severe liver damage and disseminated intravascular coagulation.
In the fourth day after receiving the new drug, despite the professional
medical care, the young patient died. His death was the direct result of a
massive immune response to an adenoviral vector that circulated through most
internal organs.

In conclusion, gene therapy in recent years has made a
huge step forward thanks to the continuous improvement of techniques for
introducing genetic material. Gene editing is becoming a tool that is
increasingly used to develop new therapies for onerous diseases. Unfortunately,
the reaction of the immune system to the introduction of modified genes is
still unknown. Gene therapy methods may in the future become a basic tool in
the fight and treatment of genetic diseases. At the moment, the greatest hope
is associated with the treatment of cancer and lifestyle diseases of the
circulatory system. In addition, better methods for delivering therapeutic
genes to cells are also needed because it is difficult to control and eliminate
the integration of viral genes into host cells over widely used viruses. The
development of genetic engineering, research on new nucleic acid vectors,
improving their efficiency and safety allow us to believe that perhaps in the
coming years gene therapy will become a widely available, safe and effective
form of treatment for at least some diseases, complementing conventional
methods. Gene therapy also raises ethical problems – research is conducted on
cell cultures, then on mice and then results from human experiments are
necessary. Such persons must be informed about possible risks, which are often
difficult to assess. However, the potential of research on gene therapy is
considerable and this field may become widely available and effective. Then it
will be a complement to surgical, radiological and conventional methods.

Gene therapy is a very modern and promising treatment technique that can
bring many positive solutions to medicine. However, attention should be paid to
the fact that genetic therapy is still under development, clinical trials are
being carried out and it is not yet widely used.

References

• Coune, P., Schneider, B. and Aebischer, P. (2012). Parkinson’s Disease: Gene Therapies.
• Dalgleish, A. (1997). Why: Gene Therapy?. Gene Therapy, 4(7), pp.629-630.
• Fda.gov. (2018). U S Food and Drug Administration Home Page. [online] Available at: https://www.fda.gov/ [Accessed 9 May 2018].
• Fischer, A. (2016). Gene therapy: Myth or reality?. Comptes Rendus Biologies, 339(7-8), pp.314-318.
• Mavilio, F. and Ferrari, G. (2008). Genetic modification of somatic stem cells. The progress, problems and prospects of a new therapeutic technology. EMBO reports, 9, pp.S64-S69.
• Medicalnewstoday.com. (2018). GDPR consent required. [online] Available at: https://www.medicalnewstoday.com/articles/317343.php [Accessed 28 May 2018].
• Nathwani, A., Reiss, U., Tuddenham, E., Rosales, C., Chowdary, P., McIntosh, J., Della Peruta, M., Lheriteau, E., Patel, N., Raj, D., Riddell, A., Pie, J., Rangarajan, S., Bevan, D., Recht, M., Shen, Y., Halka, K., Basner-Tschakarjan, E., Mingozzi, F., High, K., Allay, J., Kay, M., Ng, C., Zhou, J., Cancio, M., Morton, C., Gray, J., Srivastava, D., Nienhuis, A. and Davidoff, A. (2014). Long-Term Safety and Efficacy of Factor IX. The New England Journal of Medicine.
• NATURE International weekly journal of science. (2016). Gene-therapy trials must proceed with caution. [online] Available at: https://www.nature.com/news/gene-therapy-trials-must-proceed-with-caution-1.20186 [Accessed 28 May 2018].
• U.S National Library of Medicine (2018). What is gene therapy?. [online] Genetics Home Reference. Available at: https://ghr.nlm.nih.gov/primer/therapy/genetherapy [Accessed 28 May 2018].
• Wellcome.ac.uk. (2018). UK legislation and regulation governing the use of gene editing | Wellcome. [online] Available at: https://wellcome.ac.uk/what-we-do/our-work/uk-legislation-and-regulation-governing-use-gene-editing [Accessed 9 May 2018].
• Wirth, T., Parker, N. and Ylä-Herttuala, S. (2013). History of gene therapy. Elsevier.
• Wong, M., Hawthorne, W. and Manolios, N. (2010). Gene therapy in diabetes. pp.165–175.