gene therapy

gene therapy n the insertion of usu. genetically altered genes into cells esp. to replace defective genes in the treatment of genetic disorders or to provide a specialized disease-fighting function (as the destruction of tumor cells)

gene therapist n

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treatment directed to curing genetic disease by introducing normal genes into patients to overcome the effects of defective genes, using techniques of genetic engineering. The most radical approach would be to do this at a very early stage in the embryo, so that the new gene would be incorporated into the germ cells (ova and sperm) and would therefore be inheritable. However, this approach is not considered to be either safe or ethical, because the consequences would affect all descendants of the patient, and it is not being pursued. In somatic cell gene therapy the healthy gene is inserted into somatic cells (such as the haemopoietic stem cell of the bone marrow) that give rise to other cells. All the surviving descendants of these modified cells will then be normal and, if present in sufficient numbers, the condition will be cured (the defective gene will, however, still be present in the germ cells).

At present, gene therapy is most feasible for treating disorders caused by a defect in a single recessive gene, so that the deficiency can be overcome by the introduction of a normal allele (therapy for disorders caused by dominant genes (e.g. Huntington's disease) would require the modification or replacement of the defective allele as its effect is expressed in the presence of a normal allele). Examples of such recessive disorders include adenosine deaminase (ADA) deficiency and cystic fibrosis. Gene therapy trials for the former condition have already begun: lymphocyte stem cells are isolated from the patient, using monoclonal antibody, and incubated with retrovirus that have been genetically engineered to contain the normal ADA gene (see vector). This gene thus becomes integrated into the stem cells, which - when returned to the patient's bone marrow - can then produce normal lymphocytes. A similar technique has been used in treating patients with severe combined immune deficiency and is feasible for other blood disorders, such as sickle-cell anaemia and thalassaemia.

Clinical trials for the gene therapy of cystic fibrosis involve using liposome to introduce the normal gene into the lungs of sufferers via an inhaler.

Gene therapy for certain types of cancer is also undergoing clinical trials. Here the approach is aimed at introducing into the cancer cells tumour-suppressing genes, such as p53 (which prevents uncontrolled cell division), or genes that direct the production of substances (such as interleukin 2) that stimulate the immune system to destroy the tumour cells.

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manipulation of the genome of an individual to prevent, mask, or lessen the effects of a genetic disorder. The defective function may be replaced by introduction of genetic material into targeted cells, or the defective gene itself may be corrected by targeting a recombinational event to replace all or part of the defective gene with a normal DNA sequence.