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Gene therapy

Gene therapy is the introduction of genes in to a person's DNA in order to treat disease. Gene therapy is an emerging medical technology that involves the addition of DNA to the human genome in order to replace a defective gene or to provide a gene the body can use to fight disease. Although the technology is still in its infancy, it has been used successfully to treat genetic disorders such as those encountered by children with immune deficiencies. Background In the 1980s, advances in genetics had already enabled human genes to be sequenced and cloned. Scientists looking for a method of easily producing proteins, such as the protein deficient in diabetics - insulin, investigated introducing human genes to bacterial DNA. The modified bacteria then produce the corresponding protein, which can be harvested and injected in people who can not produce it naturally. Scientists took the logical step of trying to introduce genes straight in to human DNA, focusing on diseases caused by single-gene defects such as Hemophilia, muscular dystrophy and sickle cell anemia. However, this has been much harder than modifying simple bacteria, primarily because of the problems in carrying large sections of DNA and delivering it to the right site on the genome. Types It is possible to alter the DNA of somatic (normal body) cells or germline (sperm or egg) cells. In somatic gene therapy, genes are delivered in to body cells where they would be used to produce proteins. In highly controversial germline engineering, DNA contained in sperm or egg cells are changed so that the patient, and any offspring that he or she may produce, will grow up with a modified genome. This type of gene therapy is not being actively investigated in humans due to the ethics of changing DNA that would be inherited by countless generations in the future. Somatic gene therapy can be broadly split in to two categories: ex vivo (where cells are modified outside the body and then transplanted back in again) and in vivo (where genes are changed in cells still in the body.) Ex vivo The ex vivo approach was the first to be put in to practice. In 1990 trials were run designed to treat children with an inherited immune defficiency, as well as children or adults with high serum cholestorel levels. Cells were removed from the patients body and incubated with vectors to introduce the genes. Vectors are simply any mechanism that allows genes to be carried in to the genome. Many vectors are based on viruses. After modification, the cells are transplanted back in to the patient where they would hopefully replace the defective gene in the original genome. The new gene would correct the protein deficiency. This technique is best used for diseases where the desired cells can be extracted easily, such as the blood or liver. In vivo For in vivo techniques the challenge of inserting the genes is even greater. The vector carriers have a difficult task to complete: they must deliver the genes to enough cells for results to be achieved; they have to remain undetected by the body's immune system; and they must deliver the genes in to the precise spot on the genome for the body to recognize it and produce the corresponding protein. Much hope has been placed in viruses to carry the DNA. After all this is what viruses do naturally - change cell's DNA in order to allow themselves to reproduce. Through millions of years of evolution viruses have developed very sophisticated ways of doing this. There are two classes of virus which look promising - retroviruses and adenoviruses. Retroviruses are small RNA based viruses. They reproduce by integrating their RNA in to the host's DNA. Scientists have modified these viruses' genetic code so that non of their natural proteins are produced, meaning they can not replicate and damage the host. Because retroviruses target only fast growing cells there are being investigated with an aim to developing cancer treatments. RPR Gencell (a french pharmaceutical company) conducted experiments injecting retroviruses in to lung cancer patients. After the injections of vectors containing p53 - a gene that suppresses tumours - directly in to the cancerous tissue, the tumours stopped growing and were broken down by the body. Adenoviruses are larger DNA based viruses. These can hold more genes and are not limited to just targetting fast-dividing cells. However because the larger size inevitably makes them more difficult to manipulate. A problem affecting all virus-based vectors is recognition by the immune system. When familiar viruses are detected in the bloodstream the body sends antibodies to bind to and consume them. A second problem is the unpredictablity of where the virus inserts the gene in to the DNA. If the gene is inserted in the wrong place - for example inbetween an important gene, or within intron regions that are rarely read - then the cell could start behaving irregularly and the engineered gene would not be expressed. Scientists are researching an interesting way of bypassing the DNA problems by actually introducing an extra chromosome in to the body. Existing alongside existing DNA, this 47th chromosone would contain the genes needed. Introduced in to the body as a large vector, it is not expected to be targetted by the immune system because of its construction.

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