Gene therapy

Gene therapy tries to cure a disease by putting a correct gene into a patient's cells to make up for a faulty one.

The first gene therapy was given in 1990, to a four-year-old girl with SCID (severe combined immunodeficiency), caused by a defective adenosine deaminase (ADA) gene. Her lymphocytes were taken out, given a working ADA gene using a viral vector, and returned to her. Her immunity improved, but because lymphocytes do not live forever, the cure was not permanent.

Three broad approaches:

• Gene replacement or addition: add a normal copy of the gene, for example a normal CFTR gene for cystic fibrosis, or a normal p53 gene in some cancers.
• Gene inhibition: add a gene whose product blocks a faulty gene or its harmful product.
• Gene repair or editing: correct the gene itself, with tools such as CRISPR/Cas9, which scientists borrowed from bacteria's natural defence against viruses.

Two ways to deliver the gene:

• Ex vivo: cells are taken out of the patient, given the gene in culture, and put back (cell-based delivery). It is simpler to control.
• In vivo: the gene is delivered directly into the patient's tissues.

Which cells are changed matters a great deal. Somatic gene therapy changes only body cells, so the change is not inherited. Germ-line therapy changes eggs or sperms (or very early embryos), so the change is heritable.

Hopes and limits. Gene therapy offers hope for inherited diseases and cancer. But the inserted gene may be expressed uncontrollably, or inserted in the wrong place (it could even disrupt a gene that normally prevents tumours); the effect may be short-lived; the body's immune system may reject the vector; it is costly; and it works only for diseases caused by a single gene. Ethically, changing the germ line, or using gene therapy to 'enhance' traits such as athletic ability or intelligence, is hotly debated.