Gene Therapy

Gene therapy treats a hereditary disease at its root by transferring a normal, working copy of a gene into the cells of a person who carries one or more mutant alleles, using a vector to deliver it; the normal gene is then expressed, producing a functional gene product that restores a normal phenotype. It has mainly been aimed at single-gene disorders such as cystic fibrosis and haemophilia, and matters because most genetic diseases otherwise have no effective treatment. Two strategies exist: gene augmentation therapy inserts a working copy of DNA to replace what is missing, while gene inhibition therapy instead inserts an antisense gene to silence the expression of a harmful dominant gene. Separately, therapy can target either somatic cells or germ cells. Somatic cell gene therapy introduces the functional gene into non-reproductive cells — bone marrow, blood, skin — correcting the patient permanently but leaving the change confined to that individual, never passed to offspring. Germline gene therapy instead introduces DNA into eggs or sperm, so the correction becomes heritable and passed on to later generations, which is precisely why it raises far more serious ethical concerns than somatic therapy. The landmark case that put gene therapy into practice was the treatment of ADA deficiency (a form of Severe Combined Immunodeficiency, SCID), an autosomal recessive disorder in which a missing or faulty ADA enzyme leaves T-lymphocytes unable to mount an immune response; French Anderson gave the first clinical gene therapy for it in 1990, to a four-year-old girl. Some ADA-deficient children can be treated by bone marrow transplant or by enzyme replacement therapy (injecting functional ADA directly), but neither is a permanent cure. In gene therapy itself, lymphocytes are drawn from the patient's blood, grown in culture, and infected with a genetically disabled retrovirus carrying a working human ADA cDNA; the engineered lymphocytes are then reinfused into the patient. Because th …