Gene therapy 27/8/02. By Richard Twyman The treatment of a disease by introducing DNA into the cells of the patient.

The transfer of DNA is usually achieved either by mixing the DNA with a substance that enhances its uptake or by packaging it inside a disabled virus (a virus that can carry DNA into a cell but cannot cause a disease). Gene therapy may be carried out by first removing cells from the patient and then re-introducing those that have been appropriately modified. Alternatively, the direct introduction of DNA into the patient's body may be the only effective strategy.

There are several types of gene therapy:

Gene augmentation therapy

This is appropriate for the treatment of inherited disorders caused by the loss of a functional gene product. The aim is to add a functional copy of the lost gene back into the genome and express it at sufficient levels to replace the missing protein. It is only suitable if the pathogenic effects of the disease are reversible.

Gene inhibition therapy

This is suitable for the treatment of infectious diseases, cancer and inherited disorders caused by inappropriate gene activity. The aim is to introduce a gene whose product inhibits the expression of the pathogenic gene or interferes with the activity of its product.

Killing of specific cells

This is suitable for diseases such as cancer that can be cured by eliminating certain populations of cells. The aim is to express within such cells a suicide gene, whose product is toxic. One approach is the expression of an enzyme that converts a harmless prodrug into a highly toxic molecule. Another is the expression of a protein that makes the cells vulnerable to attack by the immune system. It is very important to ensure that suicide genes are appropriately targeted, otherwise the therapy would result in widespread cell death.

Somatic and germ line gene therapy

There is an important distinction between somatic gene therapy (DNA transfer to our normal body tissue) and germ line gene therapy (DNA transfer to cells that produce eggs or sperm). The distinction is that the results of any somatic gene therapy are restricted to the actual patient and are not passed on to his or her children.

There are some arguments in favour of germ line gene therapy (for example, it would allow the correction of disease-causing mutations that are certain to be passed on) but many more arguments against.

The principle objections are:

• The technology is imperfect. The effects of gene transfer are unpredictable and, even if the target disease was cured, further defects could be introduced into the embryo.
• Denial of human rights. Individuals resulting from germ line gene therapy would have no say in whether their genetic material should have been modified.
• Potential abuse. Germ line gene therapy could by used not only to eliminate disease, but also to enhance favourable characteristics and suppress unfavourable ones. On a small scale, this would result in a generation of 'designer children', with traits chosen by their parents. On a large scale, gene therapy could result in eugenics - manipulation of the genetic properties of a population.

Photo credit: University of Edinburgh