Gene Therapy Page |1

Gene Therapy Julie C. Casper Usha Palaniswamy Introduction to Biology March 3, 2014

Gene Therapy Page |2 Gene Therapy Biological Basis The biological basis of gene therapy involves introducing a healthy gene into a patients cells in order to replace a mutated gene that isnt functioning properly. Though the process of gene therapy is still relatively new, it has been proven in a number of cases that it can help fight or even prevent diseases such as: immune-deficiencies, hemophilia, Parkinsons, cancer and HIV (Gene Therapy, 2013). It is feasibly impossible to deliver healthy genes directly to a patients cell; therefore, delivery is done by using genetically altered carriers called vectors that carry normal human DNA. These vectors are altered viruses and are most commonly used today (Gene Therapy, 2013). Viruses have transformed themselves in such a way that they are able to sheathe and deliver genes to human cells pathogenically; of which scientists have tried to reproduce this ability in order to manipulate viral genomes into removing disease-causing genes and replacing them with therapeutic ones (Gene Therapy, 2013). Because a patients cells cant be directly targeted with healthy genes, doctors must send infected vectors directly to a patients liver or lung cells, which are considered target cells (Gene Therapy, 2013). The target cell then returns to a normal state due to a functional protein product delivered from the therapeutic gene. Most all cells in a human body are comprised of genes, therefore pinpointing them as potential targets to receive gene therapy. The cells are divided into two separate categories: somatic or germ line, which are transformable. Somatic cells are most of the cells found in the human body, and germ line cells are eggs or sperm. Germ line cell therapy will result in permanent transformations of cells and will be passed down to later generations. This type of treatment, if administered during pre-implantation diagnosis or in-vitro fertilization, could cause the gene

Gene Therapy Page |3 transfer to occur in all cells of a developing embryo. The gene transfer thereby causes permanent therapeutic effect for all who inherit the target gene, which could possibly lead to total eradication of some diseases within a particular family line (Gene Therapy, 2013). Unlike germ line cell therapy, somatic cell therapy is said to be a more safe and conservative route to take. Somatic cell therapy is different because it is only applied to targeted cells within the patient who is actually being treated and is not transferable through inheritance. Additionally; this form of therapy is not always permanent, thus causing the requirement of having repeated treatments throughout a patients life in order to maintain the effects of the treatment. This therapy is the most appropriate therapy for such disorders as: cystic fibrosis, muscular dystrophy, cancer, as well as some infectious diseases. This treatment can also be used in utero in order to treat or even correct life-threatening disorders in unborn babies. (Gene Therapy, 2013) Germ line gene therapy and somatic gene therapy are extremely different in the fact that germ line gene therapy cells will transfer to offspring and continue to transfer to future generations, while somatic gene therapy is reserved only for the patient receiving the therapy and it is not transferred to offspring. Germ line gene therapy is also considered highly controversial and is referred to by some as playing God and thereby has never been used on humans. To date, all gene therapy procedures have been restricted only to somatic cells. There are two categories of somatic gene therapy used today - x vivo and in vivo. Ex vivo therapy involves exposing cells while outside of the body to the virus carrying the desired gene. Once the virus enters the cells and inserts the desired gene into the cells DNA , the cells will then grow in a laboratory and will then be returned to the patient by injection into a vein (Gene Therapy, 2013).

Gene Therapy Page |4 In vivo gene therapy involves genes getting changed in cells while still in the patients body. Social and ethical implications It has already been stated that germ line cell therapy is highly controversial because many view it as humans trying to play God. People see it as being unnatural and there is concern regarding the technical aspects of the therapy itself. There are additional concerns that the genetic changes propagated by germ line gene therapy could actually be deleterious and harmful, with the potential for unforeseen negative effects on future generations (Gene Therapy, 2013). Other social and/or ethical implications come from a type of gene therapy referred to as gene doping, which is of particular interest to athletes because of its ability to restore lost muscle mass due to age or disease. This type of therapy is referred to as gene doping by the World Anti-Doping Agency (WADA), because it works much the same as steroids. (Gene Therapy, 2013) There is much debate about gene doping because of the complex ethical and philosophical issue of what defines it, especially with regard to the bioethical debates that comes with human enhancement. As with recreational uses of steroids, many in the business of sports fear that gene doping could replace the use of steroids and give those who use it an unfair advantage over those who dont. In the business of sports, athletes are continuously screened for steroid use. In the past, if athletes were to submit themselves to undergo gene doping therapy, there would be no way to prove the person had received the treatment because treatment doesnt involve putting anything unnatural inside the body. Therefore, nothing would be detected in the persons blood or urine. The debate on gene doping has many ethical and controversial issues

Gene Therapy Page |5 because it can provide athletes a source of erythropoietin (EPO), which is a hormone that promotes the formation of red blood cells that is already widely abused in sports (Gene Therapy, 2013). The social and ethical implications of this therapy are so controversial that in 2001 the International Olympic Committee Medical Commission (IOC) met to discuss the implications this therapy has relative to sports. In 2002, WADA met to discuss genetic enhancement and in 2003 and 2004 they included and formalized a prohibition of gene doping within their World Anti-Doping Code. In 2004, the Netherlands Centre for Doping Affairs created an entire publication addressing gene doping therapy, on page five of the publication it reads,
Gene Therapy for Sports Doping

The elucidation of the complete human genome with approximately 3,000 different genes leads to new possibilities for diagnosis and prevention of a wide variety of diseases. In addition, this knowledge may be used for the design of new therapeutics, including gene therapy, based on the DNA sequence information. The principle of gene therapy is based on the delivery to a cell, of a therapeutic gene which may compensate an absent or abnormal gene. The genetic material (DNA) is mostly encapsulated and is introduced into the body by direct injection into the target organ. Gene therapy is currently an experimental therapy and its use is strictly regulated. In the Netherlands, clinical studies need approval from two offices: Central Committee on Research Involving Human Subjects (CCMO) and Committee on Genetic Modification (COGEM). (Haisma, 2004) In attempt to prevent gene doping therapy from becoming the next and newest craze in doping, the World Anti-Doping Agency (WADA) has asked scientists to work with them to find ways to prevent it from growing in popularity. WADA is so serious about the prevention of gene doping therapy in humans, for boosting athletic performance, that they have begun hosting annual meetings to raise awareness of this controversial topic. At their last meeting in Stockholm, delegates drafted a declaration on gene doping which included forceful language discouraging its use for the sole purpose of increasing athletic performance. Most recently,

Gene Therapy Page |6 German scientists have developed blood tests that are capable of detecting someones participation in gene doping therapy. This breakthrough is the first direct method developed using conventional blood samples to detect doping from gene transfer. Even after 56 days after gene doping has taken place, a blood test can still reliably detect gene doping (Science Daily, 2010). The new blood test provides simple yes or no answers based on the detection of transgenic DNA. Transgenic DNA or tDNA does not stem from the person being tested but has been transferred into their body often via viruses in order to create performance-enhancing substances such as erythropoietin (EPO) for forming red blood cells (Science Daily, 2010). The test will detect the tiniest of traces of transgenic DNA in the blood. Personal viewpoint My personal viewpoint on gene therapy is I find it to be a phenomenal breakthrough in science. I can see why some people might see it unethical to practice germ line cell therapy as it is playing Gods role in creating or fixing life; however, if it can cure diseases and possibly eradicate them entirely from the planet, why not? However, I feel more testing must be done to prove no harmful side effects could occur. I do feel germ line cell therapy is not far from becoming a part of everyday life in the medical profession, but I hope all possible outcomes, good and bad, are thoroughly investigated and no stone is left unturned. Somatic gene therapy has proven beneficial to treating and sometimes curing diseases; however for the most part, the treatment is considered a temporary fix and ongoing treatments have to be submitted throughout a patients life. Thats why I have hopes that germ line cell therapy will soon become an accepted treatment by all, because of its ability to cure diseases permanently and because genes produced from the treatment are passed down to future generations within the bloodline of the treated patient. This treatment could lead to many diseases being cured permanently and never

Gene Therapy Page |7 to return. This almost sounds too good to be true, and though I would welcome and be accepting of its use, Im not convinced that I will see it happen in my lifetime. My personal opinion is, if something can be proven without a shadow of a doubt to cure any disease without any repercussions, then it should be an acceptable choice of treatment. Why should anyone, anywhere suffer if they dont have to, especially when there are therapies available to fight or prevent diseases? Nothing, not even ethics or societal unacceptance should prevent successful treatment to saving someones life. I personally hope I see germ line gene therapy become a revolutionary treatment in curing such diseases as: immune-deficiencies, hemophilia, Parkinsons, cancer, HIV, cystic fibrosis, muscular dystrophy, cancer, as well as some infectious diseases.

Gene Therapy Page |8 References Gene Therepy Net. (2013). Retrieved March 2, 2014 from http://www.genetherapynet.com/what-is-gene-therapy.html Haisma, H.J. (2004). Topical Publication: Gene Doping. Retrieved March 2, 2014 from http://www.genedoping.com/docs/Gene%20Doping.pdf Science Daily. (Sep. 3, 2010). Gene Doping Detectable with a Simple Blood Test. Retrieved March 2, 2014 from http://www.sciencedaily.com/releases/2010/09/100902121221.htm