Gene Therapy - Positive and Harmful Side Effects - Literature review Example

Gene Therapy Client Inserts His/her Name Client Inserts Grade Course Client Inserts Tutor’s Name 02/11/2011 Many techniques for treating diseases that seemed untreatable decades ago have been developed as medical technology progressed into the 21st Century. The identification of DNA as the genetic blueprint of life is perhaps the most significant advancement in biological science. This development was followed by that of biochemical techniques for sequencing and manipulation of the alleged genetic materials. Science has shown that proteins are the fundamentals for all developments and those genes in the DNA encode for these proteins. The potential for greater achievement has been unlocked in the field of medicine especially with the completion of the Human genome project. Correction of genetic errors at the DNA level by providing defective genes with a functional copy of the relevant gene has made it possible to come up with treatments which correct the cause of the condition other than relying on the symptoms (Drake 2009). Kresina (2001) argues that gene therapy science has developed from significant research advances in the fields of clinical medicine, genetics, human genomics, and molecular biology. Hence, gene therapy can be defined as the use of genetic manipulation for treat of diseases. It is basically involved with the correction of genetic defects by administration of functional genes (Drake 2009). The concept is the introduction of a gene with the ability to prevent the progression of a certain disease. Even tiny errors in the arrangement of gene nucleotide bases may lead to the production of proteins or enzymes that works improperly. Sometimes the needed compounds might not be produced at all (NCABR) Gene therapy approach was first used in 1990 to treat a genetic disorder- Adenosine Deaminase deficiency (ADA) in children. According to (NCABR) Genetic disorders can be described as medical conditions normally caused by an error in a person’s genetic material. Some disorders cause medical problems noticeable at birth while other genetic disorders are only evident during the childhood or adulthood stage. So far scientists have been able to identify more than 9,000 genetic disorders some of which are common while others are extremely rare. Gene therapy techniques have been developed and some advanced to effectively treat these genetic disorders (Primrose & Twyman 2006). According to Ratledge & Kristiansen (2006), gene therapy treatment can be categorised into two: somatic cell gene therapy and germline therapy. In somatic cell gene therapy, blood cells from a person with a genetic disease are obtained and then normal genes are introduced into the defective cells. This type of gene therapy only affects the somatic cells that are not involved in reproduction. The alteration does not affect the individual’s genetic makeup. Therefore, it does not prevent the disease from occurring in the next generation. The effects of somatic cell gene therapy do not last very long hence needs to be done several times over the course of the patient’s life (Gross 1999).The technique has many applications to human health. DNA vaccines, a variant of somatic cell gene therapy allow cells of the immune system to fight certain diseases in a manner similar to conventional vaccines. Physicians try correct genetic defects that cause ADA and PNP enzyme deficiencies (Gene therapy) Germline gene therapy on the other hand takes place on reproductive cells. It is done by genetic modification of germ cells that passes the change on to the next generation. In the chapter Gene therapy the objective of this type of therapy is to create beneficial genetic changes that are not transmitted to offspring. Once these genes are introduced into a reproductive cell, descendant cells can inherit the genes. Germline gene therapy only needs to be done once to be permanent. This can be done for example by treating a pre-embryo that carries a genetic defect before being placed back in the mother through IVF. Germline gene therapy can also be done by treating adult sperm and egg cells thus preventing gene defects from being passed on to children (Gross 1999). According to OTQEF, two methods exist for inserting genetic material into human chromosomes. The first, ex vivo technique, is done by surgically removing cells from the affected tissues, injecting or linking the new DNA that will correct the disease into the cells and let them divide in cultures. The new tissues are then placed back into the affected area of the patient. Surgeons usually culture the patient’s bone marrow given that it produces the blood that is circulated into the body. The surgery is normally performed twice normally extracting the bone marrow and replacing it back after the culture is done (Barnum 2005). The in vivo technique on the other requires no surgery or even anaesthesia. The therapeutic DNA is injected directly into the body cells through the use of one or two viruses. The very simple retrovirus is mostly used in this case. Adenovirus is also used given that it is somehow similar to retrovirus the only difference being its effects are much more immediate and the effects wears off within weeks (OTQEF). Several other gene therapy techniques are also used to correct defective genes. According to Billman (1996), the effectiveness of gene therapy depends upon the lifespan of the target cells. Sometimes the gene therapy process has to be repeated several times if the targeted cells only survive for a short period. In (HGPI), the techniques include: Inserting a normal gene into a nonspecific location within the genome to replace a non-functional gene. Swapping abnormal genes for a normal gene through homologous recombination. Repairing abnormal genes through selective reverse mutation thus returning the genes to its normal function. Altering the regulation of a particular gene. The first technique; inserting a normal gene into a nonspecific location within the genome to replace a non-functional gene is the most commonly used technique. In this technique, a vector must be used to deliver the gene to target cells. The health genes introduced should not be accepted by other cells of the body. Primary vectors in this case are viruses due to their pathogenic ability to insert DNA into human cells (Borem, Santos & Bowen 2003). These viruses are normally genetically altered to carry human DNA. The most promising vectors in this case are adeno-associated viruses (AAV) given that they lack pathogenicity and toxicity, are able to infect dividing and quiescent cells of diverse tissue origins. They also have the potential for site-specific integration into the host chromosome resulting in long-term gene expression. (Keiper 2011). The ability to repair mutated genes is another area in gene therapy that is making a tremendous progress. Instead of inserting a therapeutic gene, mutated genes are repaired thereby bypassing the concern of oncogenic risks whereby the therapeutic gene may insert itself within another gene thus disrupting the gene function therefore increasing the chances of developing oncogenic diseases. Gene repair was first utilized successfully in mice with a heredity disease, tyrosinemia type 1 (HT1) which is caused by lack of fumarylacetoacetate hydrolase (FAH) (Keiper 2011). Several methods of transporting genes into cells have been developed by researchers. Attaching healthy genes to genetically modified viruses is the commonest technique used. A vector which in some instances is also referred to as a carrier molecule is used to transport the gene into the “targeted cells” of the patient (Joyal 2007). The vectors carry the genes into a cell’s nucleus and integrate them into the genetic material of the infected cells. Science has shown that viruses can be used as vectors for the delivery of healthy genes. The viruses used by researchers as vectors include the following: Retroviruses, the first virus vectors to be used in gene therapy experiments are unique in that they use RNA as their principal carrier of genetic information instead of using the DNA. Retroviruses use an enzyme called reverse transcriptase to make a copy of their gene’s DNA. The DNA copy is then incorporated into the infected cell’s DNA by other enzymes (Gross 1999). Although being used in many gene therapy experiments, retroviruses present problems by the fact that they are able to invade only cells that are actively dividing thus limiting their potential targets to skin cells, stem cells, blood cells, and other fast growing tissues. Caution has to be taken when using retroviruses because they might attack inappropriate cells. Researchers have begun injecting altered retroviruses directly into tissues where the corrected genes are needed (NCABR). Adano- Associated Viruses (AAV) has been flagged as one of the promising vectors by Researchers. It infects a broad range of cells both dividing and none dividing. This vector is being studied to treat haemophilia, a hereditary blood disease in human. The limitation with these vector is that it is small capable of carrying only two genes in its natural state (NCABR).The risk involved with this viral vector just like any other is its capability once inside the body to recover pathogenic ability causing diseases, toxicity or even an immune response that reduces gene therapy effectiveness due to immunological memory of viruses. Gene therapy has also been known to cause other genetic diseases through non-site-specific integration of a therapeutic gene (Keiper 2011). Cystic fibrosis, a disease caused by a mutated gene that impairs the lung fuction can be treated with this viral vector technique. Here, healthy genes are inserted directly into the lining of the bronchial tube. The technique is now targeted to treating those people with muscular dystrophy (NCABR). Adenoviruses are now being used as vectors by some researchers to avoid the problem of inserting genes at the wrong sites. Once their disease casing genes have been removed, adenoviruses carry healthy genes into the nucleus of cells but do not integrate them into that cell’s DNA (Billman 1996). This vector is able to infect a broader range of cells even those that divide more slowly e.g. lung cells. They are however more likely to be attacked by the patient’s immune system. This has been observed in their attempt to treat cancer of the liver and ovaries (NCABR). Herpes Simplex Virus, the cause of the common cold sore has been found by scientists to have a large genome compared to other virus vectors. More than one therapeutic gene can be inserted in a single virus enabling the treatment of diseases caused by more than one gene defects. The vector is best because it is capable of infecting a wide range of tissues. The only problem with this vector is crytopathic i.e. it kills the cells that it infects. Scientists are currently developing a form of herpes simplex virus whose cell-killing ability have been removed (NCABR). Many controversial issues; ethical, moral and legal, have arisen in the near past concerning the practice of gene therapy. A section of people believe that gene therapy is the only successful weapon to fight all genetic diseases while others believe that gene therapy arena will turn human species into technologically designed products reducing the human race (Joyal 2007). Germline gene therapy in particular is in the centre of a moral dilemma on gene therapy. The argument is based on the fact that the future generation will be damaged if unanticipated problems or mistakes in germline gene therapy are passed to forthcoming generation. This is further supported by the belief that alteration of patient’s genetic information may result in long-term side effects that are unpredictable. Possible changes in the human gene pool have also been ethically criticized (Billman 1996). Billman (1996) purports that somatic cell gene therapy will have great benefit treating some diseases suffered by human beings. He further argues that it will be of great economic benefit for those diseases that will otherwise require long-term institutional care. If gene therapy could help by eliminating diseases like AIDS, cancer, Alzheimer disease, and other diseases, this would end the unnecessary suffering. Gene therapy, a new technology might have some unforeseen risk thus needs to be regulated legally. Protocols need be reviewed and approved by a relevant authority in the country that it is being developed. The recombination DNA Advisory Committee (RAC) is a review board created to regulate research projects involving gene therapy protocols (Nichole 2002). All the research findings including any harmful side effects need to be reported to the said authority. Informed consent needs to be applied to all the subjects under study. Subjects or their guardians must be informed fully about the whole procedure and the type of aspects to be expected (NCABR). Other legal issues associated with gene therapy involve the right of privacy of people with genetic diseases. The above information clearly shows that there are many thoughts that needs to insight this procedure and caution needs to be taken when considering a lifelong altering gene therapy (Gross 1999). List of References Barnum, S.R., 2005. Biotechnology: an introduction. 2nd ed. California: Thomson/Brooks/Cole. Billman. K., 1996. Human Gene Therapy. [Online] Available at: [Accessed 1 November 2011]. Borem, A., Santos, F.R., and Bowen, D.E., 2003. Understanding biotechnology. New Jersey: Prentice Hall. Drake, D. M., 2009. Biochemical investigation of the intracellular trafficking of non-viral and hybrid gene therapy vectors. Cambridge: ProQuest. Gene Therapy. [Online] Available at: [Accessed 30 October 2011]. Gross, M., 1999. Human Gene Therapy. [Online] Available at: [Accessed 31 October 2011]. Human Genome Project Information, Information, 2011. Gene Therapy. [Online] Available at: [Accessed 30 October 2011]. Joyal, A., 2007. Gene Therapy: An Advice in Science. [Online] Available at: [Accessed 31 October 2011]. Keiper, A., 2011. The Progress of Gene Therapy: Genomics and Medicine. [Online] Available at: [accessed 31 October 2011]. Kresina, T. F., 2001. An introduction to molecular medicine and gene therapy. New Jersey: John Wiley and Sons. Nichole, D.S.T., 2002. An introduction to genetic engineering. 2nd ed. Cambridge: Cambridge university Press. North Carolina Association for Biomedical research, Issue Brief: Gene Therapy. [Online] Available at: [Accessed 1 November 2011]. Oracle ThinkQuest Education Foundation, Gene Therapy. [Online] available at: [Accessed 1 November 2011]. Primrose, S.B., and Twyman, R.M., 2006. Principles of gene manipulation and genomics. 7th ed. Oxford: Blackwell. Ratledge, C., and Kristiansen, B., 2006. Basic Biotechnology. 3rd ed. Cambridge: Cambridge University Press. Read More