Gene Therapy using Viral Vectors
This process also has advantages over the liposome method such as the viral method has greater efficiency and a higher success rate, according to John Chiorini of the National Institute of Health.
The steps for viral gene delivery involve:
- Isolate the ‘healthy’ allele from somebody who is not a sufferer of the disease to replace the defective allele in in the sufferer’s cells.
- Remove the DNA sequence for replication in the virus and replace it with the healthy gene.
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The virus attaches to the cell membrane and injects the DNA into the sex cell.
- This plasmid enters the nucleus through the nuclear pores and is incorporated into the sufferers existing genes.
How the DNA takes effect
After either of these processes has taken effect, transcription of the new DNA takes place. The new DNA is transcribed by nucleotides binding to the strand to form mRNA. The mRNA leaves the nucleus to the ribosome for translation where the protein is made which is able to combat the defective cell. An example of this would be in Cystic Fibrosis sufferers where the mRNA codes for the CFTR Protein needed to regulate the water content of mucus.
How effective is gene therapy on Huntington’s disease?
Despite this highly technical and scientific process, there are many implications on the effectiveness these methods have and how they would be adapted to combat Huntington's disease, one of which is the cost of this process.
As you can imagine, it requires a lot of time and money to even prepare resources for gene therapy. 9 out of 10 experts believe that the UK will fall behind in gene therapy because of the lack of funding the government can supply. Some scientists believe it will not be worth it if the government doesn’t increase their funds.
"Amounts like £3 million for gene therapy are almost insignificant on a national level" (1)
Dr Stephen Hart, a molecular immunologist at the Institute of Child Health.
New research has been carried out on mice and has lead to a breakthrough in the combat of Huntington’s disease. Scientists from the University of Iowa gave gene therapy drugs to mice with Huntington’s disease. They noticed that after these mice had offspring and passed on the disease, the effects of the disease were almost completely gone.
They found that providing new genetic instructions which counteracted the production of the mutated protein and a supplement of Huntington’s protein, lowered the effects of the disease on mice.
"Gene therapy in these models successfully attenuated the symptoms of Huntington's disease and increased life span." (2)
Benjamin F. Biaggini, Professor of Biological Sciences.
Benefits and Risks
One of the most important questions to take into consideration is whether the ‘benefits outweigh the risks’. Gene therapy has a wide variety of balanced benefits and risks. This is what makes it such a controversial subject.
The main benefit of gene therapy is that it can effectively reduce the symptoms of diseases, diseases such as Huntington's Disease, cystic fibrosis, sickle cell anaemia and many others. This could be a massive medical breakthrough
Another benefit is that if germ-line therapy research is continued, we could be able to completely wipe out diseases by removing the gene before it starts to replicate. This is similar to stem cell research as it is working with early embryos to eradicate the disease before it is too late.
However, gene therapy is not 100% safe especially with the stage it is at now. We do not want to endanger the lives of patients if they can cope with the disease they have now. A lot more time and money needs to be spent before germ-line gene therapy can be performed.
There are also many unknown risks which could occur after trials of gene therapy, one is that the virus vector process could lead to leukaemia. The same study also shows that injection of plasmid DNA is random, and there were only 72% of cases where the plasmid successfully attached to the DNA.
This study shows a very offensive view to gene therapy, looking deeply into possible flaws. Below is an extract taken from the study.
“In the in vivo experiment in mice successfully transfected with L particles expressing human blood clotting factor, the protein started disappearing on day 30, and by day 42, had vanished completely. What happened to the cells that had taken up the L particles? What happened to the mice? The toxicity test carried out consisted of five four-week old mice injected with 500ug of the L particles expressing the human clotting factor 9, which were reported to have "survived for more than 2 weeks, indicating that the median lethal dose (LD50) is >20mg/kg." That meant the mice did die. Is that reassuring? What did the mice die of?” (3)
Ethical Implications
The main implication on this is if this process will be abused and become focused on genetic enhancement. Genetic enhancement is modifying the genes of a human who does not have a genetic disease or disorder, in order to improve their physical traits or abilities. This is frowned upon by many as people worry it may not be controlled and it could risk human diversity.
In a general perspective however, this idea of gene therapy can cure millions around the world today, most people believe it is morally acceptable to use this process to help destroy the effects of the disease.
In an editorial published by the magazine Christianity Today, which is clearly not neutral on the subject of genetic engineering, the practice of “designing” babies through the practice of embryo banking—which essentially involves selecting from a catalogue of desired traits—is “not morally neutral, [and represents] another step down the slippery slope toward the clear evil of eugenics” (4)
Some people see the idea of creating humans with more advantageous traits as a good thing, they believe we can reach new heights and achieve much more is this is possible.
A report by Torsten O. Nielsen states that “In the 1980s, initial discussion about human gene therapy sometimes evoked strong opposition, based on claims that it entails playing God, or violates “natural law”. A paper stated bluntly that “there is a feeling among segments of the general public that the genetic manipulation of humans is simply not an acceptable activity”. However, the public is thought to dramatically overestimate the risks of that which is unfamiliar, hard to understand, or outside public scrutiny. Technophobia regarding human gene therapy has, to a degree, subsided, and the debate has evolved to focus more on the potential benefits of such treatment. A U.S. government poll in the late 1980s found that fully 84% of Americans supported the genetic manipulation of human cells to cure fatal genetic diseases.”
(5)
Social Implications
Genetic engineering also has concerns over the society; altering genes would decrease genetic diversity. This is what has kept the human race alive for so long, it is important that not all our genes are the same because some genes hold resistance to different diseases. If all our genes were identical, it would only require one unknown deadly disease to wipe out the human race.
Scientists are concerned that misuse of genetic enhancement could destroy our society, arguing that normal people will be highly disadvantaged and will lead to social imbalance.
Others see this as a benefit to society as people will be allowed to live much healthier and fitter than before and create a positive atmosphere in our environment.
Below is an extract taken from the book, Gene Therapy by Mauro Giacca.
(6)
This extract was interesting and worth including in my report because it is up to date and written by a reliable scientist. In this extract he explains the ethical and social concerns involving gene therapy and states how germ-line therapy is a process which we should look further into and also that genetic enhancement could be manipulated in a bad way.
Alternatives
There are also many effective alternatives to gene therapy which are arguably more cost-effective than gene therapy. Perhaps one of the most popular alternatives is stem cell research. This research has been competing with gene therapy for cures to diseases since the 90’s. Stem cell research offers the chance to create a clone of a human being which does not have Huntington’s disease. This also has a lot more research needed to be done before it is deemed acceptable by society.
Another alternative is drug therapy. This therapy is already being used by most patients suffering from Huntington's disease. Drugs are very cost efficient and simple, but concern has arisen over the effectiveness on patients and these drugs cannot fully eradicate the symptoms of Huntington’s disease.
Physiotherapy is a kind of treatment that also seems to have good effects on patients. Sufferers can take part in mental and physical exercises which have proven to delay the effects of Huntington’s disease.
In my opinion, Gene therapy remains the most important way of treating Huntington’s disease, although it may require more study and analysis, the future of gene therapy for cures looks promising, and with more finance being invested in research, this could be a medical breakthrough for many genetic diseases.
Bibliography
In my Report I have made sure that I will study valid scientific journals and reports and evaluate evidence on both sides to support my question.
These websites, books and articles have helped provide information and quotes to support my issue report. Most of them are reliable and have been written by academic lecturers or scientists. However it is important to evaluate these sources so I can prove the reliability of the sources.
(28 January 2007) - This article was from a blog and the author is unidentified.
8/10- This source provides key information and data on the process of gene therapy using viral vectors and also talks about gene delivery using liposomes. This was used for the process stage of my report as it helped me to understand the stages undergone. This is a reliable case study as it shows lots of references from the text and all appear to be from scientific or academic institutes. Not much is stated about the implications this process has but it helped me explain the process in detail.
(1) (23 July 2003) - Katrina Lythgoe.
(2) (9 November 2009) - This article has been reviewed by the editors of ScienceDaily.
(3) (2004) - Dr. Mae-Wan Ho and Prof. Joe Cummins
(4) (1 March 2007) - This article has been reviewed by the editors of Christianity Today.
(5) (1997) - Torsten O. Nielsen
(6 March 2011) - This article has been revised by members of wikipedia.
(13 April 2011) - This article has been revised by members of wikipedia.
(June 2004) - Linda McDonald Glenn.
(1999) - C. Ropert.
(2007) - Nicole Smith.
(October 2008) - Anju Shandilya.
(April 2006) - Kathi E. Hanna.
(April 2009) - Parita Patel.
(13 March 2003) - This article has been reviewed by the editors of BBC Health.
(12 August 2010) – Anton Alden
(31 July 2007) - Dr Alexander Lyon.
Book:
(6) Gene Therapy – Mauro Giacca (page 283) (December 2010)
Non-Viral Gene Therapy: promises and challenges. (Article from Science Magazine November 2001)
(7/10) This article by S Li and L Huang was extracted from Science magazine in November 2001. The two authors are from the University of Pittsburgh and work in the centre of pharmacogenetics. The article was interesting and captive, and explores some key points and issues behind the topic. One problem is that the article was from almost 10 years ago and is looked upon as outdated; however this addressed important ethical and social implications which helped support my arguments in the ethical and social side.
The Frankenstein Syndrome – The ethical and social issues of genetic engineering of animals (1995) – Bernard E. Rollin.
