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Repairing genes: Technology
Replacing genesSome hereditary disorders are the result of a single defective gene. If that gene were to be replaced by an intact one, the disease would be cured. Examples of disorders caused by a single defective gene are the hereditary lung disease cystic fibrosis and the blood disorder sickle-cell anaemia. The most difficult aspect of gene therapy the official name for replacing defective genes is how to transfer the genes into the nuclei of a patient's cells. Viruses as vehiclesViruses are very suitable for transferring DNA into human cells. Over the course of their evolution, viruses have developed all sorts of tricks to infect cells. Viruses reproduce by inserting their DNA into the host cells nuclei and thus forcing the cells to make copies of the virus. The genes inducing infected host cells to produce copies of the virus are extracted from a specific virus. This virus is then the ideal vehicle for transferring genes into a cell. The replacement gene is inserted into a virus particle. The virus then infects the cells with the new gene and the disease is cured. Click here for a schematic explanation of the technology. In-vitro gene therapyIn-vitro gene therapy involves first removing a number of cells from a patient. These cells are cultured in the laboratory, where the cells are then infected with the virus containing the new gene. The infected cells that successfully incorporate the new gene into their DNA are cultured and returned to the patient. The first successful gene therapy trial involved this technique. The patient, a ten-year-old girl, suffered from a disease affecting the immune system, which made her extremely prone to infections. An intact gene was inserted into some of her bone marrow cells, which were subsequently returned to her. This small number of cells was sufficient to repair her immune system. In-vitro gene therapy has recently been very successful with children suffering from the serious immune disorder SCID. Children with SCID are extremely sensitive to infections. In the past, children with SCID would not generally survive their first year. In the last few decades, however, these children have been able to live longer as a result, for example, of injections of antibodies. However, they have still needed to live in completely sterile environments. A limited number of patients can be cured by bone marrow transplants. Until very recently, however, there has been no permanent solution for patients for whom no suitable donor is available. Some of these children have now been successfully treated via gene therapy. Gene therapy involves some bone marrow cells being removed from a patient. These cells are then infected in a laboratory by a specially developed virus containing the gene that malfunctions in children with SCID. The cells are then returned to the patient's body, with very positive results to date. Four of the five children treated so far have been able to leave their sterile rooms within three months and are considered cured. Click here for a schematic explanation of the technology. In-vivo gene therapyIn-vivo gene therapy involves virus particles being applied directly to the patient. Choosing a suitable virus ensures that only diseased cells are infected. In, for instance, the case of cystic fibrosis (a disorder primarily affecting the lungs), only the lung cells need to be treated. Although the defective gene is present in all the cells in the patient's body, it only needs to be replaced in the lungs. The first trials of in-vivo gene therapy have met with only limited success. Expectations, however, remain high. In-vivo gene therapy experiments in mice, for instance, have resulted in the blood disorder sickle cell anaemia being completely cured. |