What is Gene Therapy?
To prevent some symptoms scientists have identified various different medical treatments, this could be anything from inserting genes to orally taking a tablet, but have not found a cure, and are still facing problems in finding a permanent cure. It was not until recently scientist could provide a long term cure with the use of gene therapy.
Although gene therapy has proven many benefits, it is still a hot on-going debate. The method has been talked my many as “Violating moral codes”3. The theory is that the “bad”, missing, or damaged genes are replaced or restored by the “good” genes from the donor. This technique has been very beneficial, in the used of hereditary diseases and research. Since the Mid 90’s there have been many developments in the topic largely by the researching doctors and scientists. One of the major flaws in Gene therapy is the use of by-products like embryonic stem cells, and cloning, these are hot button topics which are capable of banning Gene therapy itself.
How would gene therapy prevent cystic fibrosis?
Gene therapy has not yet advanced, for it to cure disorders completely, but they are closer to doing so. Gene therapy targets the CFTR gene, (the gene that causes CF). The CFTR protein is found in the lining of major organs and controls the transport of chloride, water and salt across the membranes. The deregulation of salt causes the build of mucus, and stimulates bacterial growth, this then leads on to many symptoms, such as glands getting blocked and the movement of digestive enzymes.
Gene therapy treats cystic fibrosis by clearing lung infections with antibiotics and drugs to thin mucus. It is also used widely to reduce inflammation of lung tissue through the use of anti-inflammatory drugs, a substitute for pain relievers.
It also improves the absorption of food and weight gain in CF patients through digesting enzymes. Gene therapy is known for lung congestion through draining of the bronchial airway techniques, including CPT (chest physical therapy). It’s strongly recommended that CF patients regular exercise as this would benefit the health.
Gene therapy at work
Firstly a gene is inserted into the target cells (target cells are the cells that do not function). The insertion of target cells could be performed by using a genetically modified virus, carried by a vector, or by using a liposome (spherical Phospholipid bilayer).
There are many different types of viruses used, here are three Common viruses:
These different Viruses can affect have different effect on targeting and embedding the new gene.
Adenoviruses, is a virus that introduces their DNA into the nucleus of the cell, but the DNA is mot embedded into the chromosome. Figure 1.2 shows the detailed components of an adenovirus.
Retroviruses – they create double stranded DNA copies of RNA genomes. The virus integrates their genetic material, including the new gene into the chromosome of the target cell.
Herpes simplex viruses – this is a double stranded DNA virus, that infects specific cell types. This virus is known to be a common pathogen that causes cold sores.
The vector is then injected instantly into the specific tissue in the body, where it is taken up by the distinct cells. Another common way of performing this is to remove a sample of cells from the patient, and then expose it to the vector, in required conditions, and then return it to the patient.
If the treatment is successful, the new gene will then make a functioning protein to control the salt levels, and clear mucus effectively. This is all good, but I suspect there is much more risk, to future generations. The whole concept is incredible, but there are many opposing views and the safety of the concept has not yet been fully researched yet.
Solutions:
According to the Clinical research centre at Inha University “Retroviral vectors have been the most preferred gene transfer system due to its well understood biology”6. They have reviewed safety features of the vectors for gene theraphy and have also tried different methods of transferring to increase the effectiveness of the gene. Possible solutions were: targeted infection, which involves infecting target cells by retroviruses initiated by binding of the viral envelope protein to cell surface receptors. Another possible solution is local delivery which is much safer in terms of long term side effects. Targeting retroviral integration involves entering the host cell, a single-stranded viral RNA genome which has been released into the cytoplasm and converted into a double stranded DNA, then forming a large nucleoprotein structure, containing proteins necessary for localisation and insertion of viral DNA into the host genome. A much newer but developing method is “Co-expression of a Suicidal Gene”6, which used the above Herpes Simplex vector.
The above transfer methods have been successful in transferring the vector, these methods were first performed on rats at the Clinical Centre, and then after the rat had passed safe health checks the method was performed on humans and was successful and much effective. (1.2b)
Are the Solutions Working?
Figure 3
New methods of targeting the target cells with the vector where identified earlier on. The new Methods prove to be very beneficial in transferring the new allele to the target, while taking into consideration safety, side effects and effectiveness of the vector used. The above graph (figure 3) shows the quantities of viral vectors needed to satisfy the demands of gene therapy.
The figures above are likely to increase dramatically due to the number of patients who will be benefiting from treatment based on gene therapy increases. The table shows a lot of Retro and Adeno viruses as these are the most common and successful to date. Other less developed vectors like “Measles Virus”16 still face danger to the individual’s health. The safer viral vectors are being used and are fulfilling the aim of gene therapy.
Are the Methods Appropriate?
However, some transferring methods have not been too successful in transferring the allele. Some methods end up causing a virus from the vector, increasing the risk of triggering a tumour by targeting a T-cell, or displaying major side effects. This is most common in methods which have not gone through many clinical trials or enough research. I personally think it is inappropriate to use a vector which has had less than 10% clinical trials, because there is a high chance of harming the individual. Those which I think are appropriate are highlighted in green in (figure 3)
Views on Genetic Testing and is it right to alter genes.
There have been ethical questions regarding the use of gene therapy to cure cystic fibrosis. Just to be clear, there is no accepted way of deciding whether something is ethically acceptable or not.
Catholic churches have taken a stand for the use of gene therapy, however most people feel that it is okay to use gene therapy. The President of the pope, Stated gene therapy is “a very noble enterprise, because it is aimed at the actual cure of actual diseases.” 3
But others are concerned that the technique may be used for “treatment of genetic disorders”3 other than diseases. It was criticised that a child was being bullied at school for being few inches below the average height and for spending $150,000 per year to increase his height by receiving treatments from gene therapy. The father was determined to do anything; he quoted that his son must have the edge, no matter what. People are worried that it is being used for the wrong reasons.
The two types of therapy: Somatic cell and Germ line, basically “Somatic cell Therapy is altering specific body cells”2, whereas Germ line therapy is altering sperm or egg cells, so that every body cell contains the new gene. “There have been ethical objections to germ line therapy because of concerns of affecting future generations with the new gene.”15 Germ line therapy should never alter other human characteristics, because this could lead to “gender imbalances or inbreeding problems”15. Somatic cell therapy on the other hand is ethically accepted and should be an option to everyone suffering from a genetic disease.
Benefits
In my opinion, gene therapy, the disadvantages outweigh the advantages. The main benefit of gene therapy is giving an advantage to someone born with a genetic disease by replacing non-functional gene with a functional one. This could give someone a chance of living a normal life.
Curing one person cannot just cure the current generation, but cure several generations. “The first time gene therapy was ever used was when a 4 year old girl who had a severe deficiency disease.”18 This meant her immune system was non-existent and that she was vulnerable. A common cold held the possibility of killing her.
She had no hope for surviving until 15 years of age. Therapy was performed on her and they managed to cure her. Even though the girl follows up treatments, she lives a normal life when she had no hope before.
Disadvantages
Gene therapy is very expensive and has faced scrutiny for the past few years. Certain individuals are using gene therapy for cosmetic reasons, and not for what it was intended to be used for.
Some people are against prenatal screening which is usually required to check if the baby is healthy and fit, so that gene therapy can be used. However many disadvantages gene therapy might carry it is not easy to ignore the fact that it can cure somebody with a diseases and allow him or her to live a normal and healthy life.
One main source in gene therapy is the use of stem cells; these stem cells can come from an umbilical cord, bone marrow, and others places to, but the most commonly used resource is embryo’s, as there are loads of undifferentiated cells which can be used for the treatment on other individuals. This topic on usage of embryos faces problems of its own. After these embryos are used they are usually thrown away in the bin then causing more environmental problems when it then goes to the landfill.
I think that gene therapy on a whole needs more research and trials, it is expensive and it faces many problems when it comes to ethical and social debates.
Alternative Methods
Bactofection
This technique involves using bacteria for transferring the gene directly into the target organism, organ and tissue. This is called bactofection. “This technique has only been around for 25 years but is improving with more research and clinical trials.”16 The bacterial strains deliver genes localized in plasmids in the cells. The transfer delivery process involves intracellular localization of the bacteria. Plasmids contain the sequence required for the transcription and translation of the transferred genes.
The main problem with bacterification has its downsides like gene therapy, in this case unwanted side effects related to the host-bacteria interactions. The strains used contain a suicide gene which is an advantage in bacterification because the bacterium self-destructs itself. During the destruction of vectors, plasmids and vectors are released into the nucleus.
Jumping gene, a Non-viral Alternative
Researchers are saying this is a much safer, target-specific alternative to viruses in gene therapy. “PiggBac transposon”20 is a jumping gene which has close relatives in the human genome. “Piggyback transposon was five to 10 times better than the other circular pieces of DNA.”20 For example, if we wanted to add a therapeutic gene, they would put the transposon with the gene and use it to deliver the gene into the cell. Scientist have used virus for the past 20 years for the gene delivery mechanism. But according Dr Kaminski, efficiency comes at a price. Mr Dr.Kaminski said “with viruses, you don’t have control”20 (source). This has proved to be a much better technique with a non-viral alternative, because gene therapy has been halted because of major complications, including deaths. So using a non-viral alternative is more effective and also much safer.
Bibliography
Non Web based source
- Edexcel Biology AS level Student book
Author: Pearson Group Date accessed: 29/03/2011
- AS biology Concept book.
- Author: Pearson Group Date accessed: 07/03/2011
Sites
Date accessed: 06/03/2011
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(PDF)
Date accessed: 19/04/2011
Date assessed; 25/04/2011
I believe this would make a very reliable source. This website is really popular and has dedicated its website to gene related articles. The article is very informative, and the layout of the article is set in bullet points with colourful headings. The website is a charity, which has been involved in experiments, genetic research and support for individuals. This website is guaranteed to be valid and reliable.
- http://www.bionews.org.uk/page_46822.asp
Date accessed: 26/03/2011
Date assessed; 26/03/2011
I believe that the “jeans for genes” website is a very reliable source. It has a purpose of informing the public about the genes in detail, the disorders and current research. It is a very popular website with many scientific articles and a very detailed glossary. It has personal views from Researchers and doctor for variety of views. I personally like the layout and informative language of this website.
Date accessed: 06/03/2011
Date accessed: 29/03/2011
Date accessed: 04/04/2011
- http://www.eurekalert.org/pub_releases/2006-09/mcog-jgc092506.php
