Germline Therapy for Cystic Fibrosis

Is germline gene therapy the answer for cystic fibrosis?

Genetics is very important in medicine today, with over 30,000 new diagnoses of genetic disorders being diagnosed in the UK each year, as reported by Genetic disorders UK (2017). The knowledge of genetics today offers the opportunity to modify, delete and insert genes to cure and relieve symptoms of certain genetic conditions. Using vectors, it has been made possible to improve the lives of a lot of people and the possibility to improve more with new techniques such as CRISPR/cas 9. In this essay I’m going to talk about what cystic fibrosis is, how it’s caused, it’s symptoms, the types of gene therapy that are possible and the benefits of these methods and also the ethics and religious viewpoints behind the different gene therapies if they were to be used in the UK now.

Cystic Fibrosis is a genetic condition caused by a faulty gene which a person is born with. However the condition can be diagnosed at any age, most commonly within the first 3 months of being born, from stats by Genetic Disorders Trust (2017). It makes the mucus in the airway thicker which can lead to many complications such as chronic infections caused by mucus blocking the airways. This condition is inherited through a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which controls the movement of chloride ions between the cell linings of the respiratory tract. It is necessary to prevent mucus from becoming too thick, as chloride controls the movement of water within tissues. Symptoms of cystic fibrosis include persistent coughing, wheezing or shortness of breath, difficulty gaining weight and difficulty with bowel movements. There are quite a few treatments that exist for cystic fibrosis that don’t involve changing genes. Firstly, there is manual chest physiotherapy which allows gravity to move the mucus from the smaller airways to the larger ones. Secondly, the active cycle of breathing technique (ACBT) has 3 phases that help to clear mucus from the lungs through breathing control, chest expansion exercises and coughing or huffing. Finally, a high-frequency chest wall oscillation is a vest that vibrates when it’s inflated, and the vibrations help to loosen the mucus from the airways.

In order for an individual to inherit cystic fibrosis, both parents must be a carrier of the CFTR gene. However, the parents won’t know they are a carrier, this is because normal cystic fibrosis genes will be dominant over the recessive CFTR gene. The child will have a 25% chance of inheriting cystic fibrosis as there is a 1 in 4 chance during genetic crosses that they will inherit two CFTR genes leading to cystic fibrosis. If only one parent is a carrier it is possible for the child to also be a carrier. Genetic testing can determine if individuals are carriers of a faulty gene such as CFTR. Cystic fibrosis carrier testing (CFCT) is a test which can test for cystic fibrosis once the baby has been born. The advantages of this test are that the parents could get some relief if they know they are carriers of this disease and their child does not have a genetic disorder. However, if the baby does have cystic fibrosis, genetic testing could cause anxiety and worry for the patients. Therefore, a good option would be for the parents to undergo genetic counselling. This would mean that they would fully understand the condition and its symptoms. It is also important that the parents understand the treatments available to treat the symptoms and that the genetic condition cannot be prevented.

Gene therapy is a technique used to place normal genes into faulty genes, as Dr. Darryl R. J. Marcer (1990) explains in the book shaping genes “It is like fixing a hole in the bucket, rather than trying to mop up the leaking water”, pg. 272. There are two types of gene therapy that can be used; somatic and germline. Somatic gene therapy treats the tissues of a person with the genetic condition in order to relieve the symptoms e.g. bone marrow cells. This type of gene therapy means that the individual is a carrier for the defective gene and could still pass it onto their children. Somatic gene therapy is successfully being used with genetic conditions today. However, this procedure doesn’t last forever as cells will get replaced, so the process will need to be performed regularly. Germline therapy changes the genes either in sex cells or in the early embryo. This means that the individual will never carry the faulty gene as it’s been replaced and will never experience the condition. This method can also be a lot easier because during in vitro fertilization the cells are more accessible than body cells in order to be changed. Therefore, gene delivery isn’t as much of a problem as it is in somatic gene therapy. However, this form of gene therapy was banned in the UK because of the risks associated with it, the unknown long-term side effects and because of the moral and religious viewpoints people may have towards it.

In order to insert new genes into the target cells vectors are needed such as viruses, plasmids or liposomes. Vectors are molecules used to carry genetic material to the desired place in a new cell in order to alter the genetic material present. Which vector is used depends on the area needed to be treated and whether the treatment is for somatic or germline gene therapy. Six common vectors include the, Adeno-associated Virus, Adenoviral vector, Retroviral vector, Herpes Simplex Virus, Liposomes and Naked DNA. Each virus has a different function and structure. Retrovirus vectors infect only dividing cells and has a max length of inserted RNA 8,000bp whereas the Adeno-associated virus infects both dividing and non-dividing cells and has a max length of inserted DNA 5,00bp. The vector responsible for altering the CFTR gene in somatic gene therapy most commonly has been the Adenoviral vector as it targets cells in the airway epithelium and targets both dividing and non-dividing cells. However, this method isn’t the most effective as the defensive system can prevent the virus entering the cells. A new method that’s been developed is the CRISPR/Cas 9 which is the simplest and most precise way to edit DNA currently. This is because the cas 9 enzyme acts as a pair of ‘molecular scissors’ which cuts the DNA at the right location nearly 100% of the time. Therefore, meaning that CRIPR enzyme can correct the faulty gene rather than having to add more genes in or take the faulty gene out.

Cystic fibrosis could be chosen as a focus for germline gene therapy because the gene that causes it is known rather than just the target tissue and also because this gene is only a single-gene hereditary disorder. Therefore, germ-line gene therapy could eliminate/repair the faulty CFTR gene. So, cystic fibrosis wouldn’t be present in the individual anymore. There has been research carried out in 2013 by cell stem cell. This research used cultured intestinal stem cells from patients with cystic fibrosis and then introduced the Crispr gene to these cells, which then replaced the faulty CFTR gene by homologous recombination (which exchanges nucleotide sequences between similar DNA). Although this is an example of somatic gene therapy it proves that Crispr could also work for germline gene therapy. Research from the 2017 registry annual data report for cystic fibrosis revealed that the average person with cystic fibrosis will live till the age of 31. This is very young compared to the average life expectancy stated by the office for national statistics in the UK which in 2017 was 79.2 years for males and 82.9 years for females. So therefore, if cystic fibrosis was considered for germline gene therapy this condition could be completely avoided and the individuals affected could live longer and would never experience the symptoms.

When considering whether germ line gene therapy should be allowed in the UK it is important to remember the different moral and religious viewpoints that some people may have. A survey conducted by the welcome trust in 2005 said 92% agreed with somatic gene therapy, 80% agreed with germ-line gene therapy. According to this survey a lot more people agreed that somatic gene therapy should be allowed because at this point it would be the individual’s decision to carry out the gene therapy and they would know the risks and also because it could make the individual live a better quality of life. However, germline is more controversial because the individual would not have a say in the therapy it would be up to scientists and the parents. On one hand some people might think that morally that germ-line gene therapy should not be allowed at all such as Robert Sparrow from the pharmaceutical journal (2015) said “There is too much at stake. Just because we have the capability to perform enhancement it does not mean we should proceed” he explained that because of the effects that could occur when carrying out germ line gene therapy and its unknown long-term effects which isn’t fair to put a child through. He also mentioned that with the capability to change genes how far it would go leading to what some people would call ‘designer babies’ for example making a child stronger and how fair this would go in the future. He also mentioned how fair it would be as not everyone could afford this type of gene therapy. On the other hand, some people might think that morally germ-line gene therapy should be allowed in certain cases such as Glenn Cohen also from the pharmaceutical journey (2015) says “Do not block a technology that could benefit people. Genetic enhancement should be looked at on a case-by case basis – a blanket ban on the technology will do us no favors” who explains that there is a difference between treatment and enhancement. Treatment to correct a genetic condition should be allowed because this allows a person to have what every other person has, such as a normal working pair of lungs. Compared to enhancement which gives someone something above everyone else which isn’t natural e.g. extra ability for strength. He believes this could then eventually lead to a competition by simply not having genetic enhancements would lead for an individual to fall behind which is morally wrong. Peoples moral view points on gene therapy, as explained by the BBC, can also be influenced by religious viewpoints that they are taught. Such as Christians who believe somatic cell therapy is right because stewardship would mean that if it’s effective against a lot of genetic conditions so should be done in order to help others but should be careful that we are not trying to play God. The views on Germ line gene therapy are that the embryo doesn’t have full human status till 14 days old so it’s right to carry it out, so the individual won’t suffer later on in life. But they also believe it’s wrong because it would be expensive and therefore it’s not right for only the wealthy to potentially benefit from this type of treatment as this isn’t justice

To conclude, I believe that germ-line gene therapy could be the way forward for treating this condition in our society today and in the future. I believe this because as good as Somatic gene therapy is becoming in relieving symptoms, this has to be repeated often and so would cost a lot of money and females could still pass this onto their child while men would be infertile. The benefits of germ-line gene therapy means that individuals who have inherited this condition would never have to know the symptoms meaning they could have a higher quality of life and would also increase their life expectancy a lot. But, if this form of gene therapy was to be allowed I believe it should be monitored very closely to ensure what Robert Sparrow said about ‘designer babies’ not coming true and to ensure that this treatment is not done for enhancement purposes like Glenn Cohen said. If this was the case and germ-line gene therapy became legal I think it should first be done on a smaller scale first so that long-term side effects could be monitored and then offered to everyone so it’s fair to all potential individuals and not done based on wealth. This would also deter from the idea of ‘designer babies’ as cases would be looked at carefully and could lead to a bright future where cystic fibrosis and other genetic conditions could be prevented.


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         Macer, D.R.J. (1990) Gene Therapy is Another Medical Therapy 272. In: Macer, D.R.J

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