Gene Therapy - Term Paper Example

Gene Therapy Introduction DNA or deoxyribonucleic acid is the molecule in the human body that en s the genetic information (refer Figure A stretch of DNA that is necessary to make a part or a whole of a protein is known as gene. It has been estimated that humans have about 100,000 to 150,000 genes (Hecht, 2004). Whenever a particular gene is defective or absent, there is either absence of a particular protein, or there is production of abnormal protein or the amount of protein produced is insufficient. This causes diseased states. Many of these diseases can be either prevented or treated by replacing the abnormal gene, or by introducing the absent gene or by supplementing the defective gene. Using genes thus to prevent or treat a disease is known as gene therapy (Genetics Home Reference, NIH). This is an experimental technique and is done by inserting genetic material into the patient’s cells. The genes thus introduced exert their benefits by either compensating for the abnormal genes or by producing beneficial protein or by supplementing the abnormal gene (Hecht, 2004). The first gene therapy clinical trial started in 1990 (Gene therapy, genomics.energy.gov). Currently, research is going on for gene therapy by various approaches in different parts of the world for various diseases like combined immuno-deficiencies, hemophilia, Parkinsons disease, cancer and even HIV (Gene Therapy, Gene Therapy Net.com). Uses of Gene Therapy 1. Replacing absent or defective genes 2. Delivering genetic material into cells that speed the destruction of cancer cells 3. Delivering genetic material into cells that cause cancer cells to revert back to normal cells 4. Delivering genes of bacteria or virus as a form of vaccination 5. Delivering genetic material that either impedes or promotes growth of a new tissue 6. Delivering genetic material that stimulates healing of a damaged tissue (Hecht, 2004). Types of gene therapy 1. Germ line gene therapy: In this type of therapy, the genetic material is introduced into the germ cells and gets integrated into their genomes. Thus the change is heritable. 2. Somatic cell gene therapy: Only the somatic cells which are involved in the disease process are dealt with. Currently, all trials and research in gene therapy involves somatic cells (Gene Therapy, Gene Therapy Net.com). . Delivery of genes into cells There are 2 methods of gene therapy: 1. Ex vivo gene therapy: Here, gene delivery is done in cells after being removed from the body (Hecht, 2004). These cells are grown in the laboratory. The cells are than modified outside the body and then transplanted back into the body. In some research trials, cells from blood or born marrow are taken out and cultured in a laboratory. Thereafter, the cells are exposed to the virus with the desired gene. The virus infects the cells and transfers the therapeutic genetic material into the nucleus of the cells. After this, the cells are injected into the patient’s body by vein. 2. In vivo gene therapy: Here, gene delivery is done in the cells that are still in the body. The simplest method of introducing therapeutic genetic material into the cells is direct introduction into target cells. However, this method is not practical because it can be used only with certain tissues and requires large amounts of DNA. Other methods are there wherein the genes are delivered into cells by vectors like viruses or bacteria, by electroporation or tiny synthetic "envelopes" of fat molecules (Hecht, 2004). Of these, the most commonly used vector is virus. Vector is the carrier of the gene. Viruses are used as vectors to deliver genetic material to the nucleus of the cell that contains its DNA. The natural ability of a virus to enter a cell is used for this purpose. The viruses used for gene therapy are retrovirus, adenovirus, adeno-associated virus and herpes simplex virus (Gene therapy, genomics.energy.gov). While preparing the vectors for gene therapy, the DNA coding for a part or whole of the normal genes of the virus to be used as a carrier is removed and replaced with the treatment gene (refer Figure-2). The carriers are engineered in such a way that there ability to enter the cells is not lost but they cannot reproduce. Genes delivered by tiny synthetic "envelopes" of fat molecules enter the cell by cell membrane which has very high concentration of fat molecules. In electroporation, the genes are delivered into the cells by creating tiny openings in the cell membrane. This is done by using a bionic chip. The chip contains a single living cell embedded in a tiny silicon circuit (Hecht, 2004). Another method of gene therapy is where the therapeutic gene gets inside the target cell by chemically linking the DNA to a molecule that will bind to special cell receptors. After binding to these receptors, the DNA is engulfed by the cell membrane and passed into the interior of the target cell. However, this is less effective than the other methods (Gene therapy, genomics.energy.gov). Figures 1& 2: 1: DNA in a human cell. 2: Gene therapy mechanism using virus as vector (Gene therapy, genomics.energy.gov). The genetic material can be delivered by different routes. The specific route is determined by the disease. Gene therapy for cystic fibrosis is administered by inhalation. In hemophilia and cancer treatment, the gene is directly injected into the tumor (Hecht, 2004). Disadvantages of Gene Therapy 1. Short-lived nature of gene therapy: This is because many of the cells are rapidly dividing in nature. Also, integration of therapeutic DNA into the genome is usually encountered with many problems. Thus the patients may have to go in for multiple rounds (Gene therapy, genomics.energy.gov). 2. Immune response: Gene therapy triggers immune response in some patients making it difficult to administer repeatedly (Gene therapy, genomics.energy.gov). 3. Complications due to vectors: Viral vectors can introduce toxicity, immune and inflammatory responses. Also, though the viruses are engineered to be innocuous, there is always a fear that they may cause disease (Gene therapy, genomics.energy.gov). 4. There is no scope for treatment in multigene disorders like heart disease, high blood pressure, Alzheimers disease, arthritis, and diabetes (Gene therapy, genomics.energy.gov). Ethical Considerations with Gene Therapy Current gene therapy is yet in the experimental stage and no product has been approved by the Food and Drug Administration (Gene therapy, genomics.energy.gov). Recent Developments in Gene Therapy Research Gene therapy has been used to restore vision in dogs. It has also been attempted to treat Lebers congenital amaurosis, a type of inherited childhood blindness caused by a single abnormal gene. Studies have shown that tumor suppressing genes delivered in lipid-based nanoparticles reduces the number and size of human lung cancer tumors in mice. Reengineered lymphocytes have been used to attack cancer cells in metastatic melanoma and myeloid disorders. Other studies have suggested a possible cure for diseases like Hingtinton’s chorea, severe combined immunodeficiency and sickle cell diseas, thalassemia, cystic fibrosis and some cancers in the future (Gene therapy, genomics.energy.gov). Researchers are also experimenting with introducing a 47th (artificial human) chromosome into target cells. It is expected that this chromosome would autonomously stand along side the 46th chromosome without affecting its functions (Gene therapy, genomics.energy.gov). Conclusion Introduction of genetic material into the cells for therapeutic purposes is known as gene therapy. This mode of treatment is useful for diseases with gene absence, mutation or insufficiency. However this is still in experimental stage. Gene therapy offers hope to those with incurable genetic disorders. References Gene Therapy. genomics.energy.gov. Retrieved April 26, 2008 from http://www.ornl.gov/sci/techresources/Human_Genome/medicine/genetherapy.shtml Gene Therapy. Gene Therapy Net.com. Retrieved April 26, 2008 from http://www.genetherapynet.com/genetherapy.html Hecht, F. (2004). Gene Therapy - The Future Is Here! MedicineNet.com. Retrieved April 26, 2008 from http://www.medicinenet.com/script/main/art.asp?articlekey=12662 What is gene therapy? (2008). Genetics Home Reference. Retrieved April 26, 2008 from http://ghr.nlm.nih.gov/handbook/therapy/genetherapy Read More