Gene Therapy Exemplifies More Than Science Fiction

Article excerpt

One of the most exciting biomedical research innovations that will likely become routine in the next decade is "gene therapy."

The process is complicated, but basically it involves the introduction of a gene into a human cell and the transfer of that cell into the live human body to function for the lifetime of the individual.

Thus, one could think of it as a "very long-acting pill."

How is gene therapy done? There are several approaches, but most rely on inserting a piece of foreign DNA (usually human, and usually the "normal gene") into a human cell in the laboratory. Most of the systems use a viral "vector." For instance, if we wanted to restore a defective gene in liver cells, we might take a liver biopsy from a patient, grow the liver cells in tissue culture outside the body, then infect the liver cell with a virus that is known to infect liver cells. The virus, however, would be genetically manipulated so that it carries the "extra gene" into the cell.

With the gene now permanently in the liver cell, we would hope that when we reintroduce the liver cells from culture back into the patient, a "new" liver would be grown from the genetically altered cells.

For example, a patient has a defect in cholesterol metabolism, i.e., the cholesterol is metabolized in the liver. With gene therapy, one could "fix" the problem.

There are other approaches. A virus could be used that is known to infect most humans (like adenovirus, which can cause the common cold). A scientist would engineer a specific gene into the adenovirus and simply infect the patient. Once the cells lining the throat were infected with the altered virus, the cells would send the virus throughout the body, carrying the altered gene.

Other diseases would be the first targets. Gene therapy has already been used with some success in diseases that have the following characteristics.

First and foremost, they must be "single gene defects," that is, the cause of the disease must be the abnormality of a single gene. Many diseases fall into this category, especially pediatric immunodeficiency diseases such as cystic fibrosis and sickle cell anemia. These diseases are caused by a mutation in a single gene, and the loss of the function of the protein that is encoded by that gene results in disease.

And the future? Once the single gene defect systems are routine, more complex genetic diseases will be tackled, such as both forms of diabetes (types I and II), Alzheimer's disease, obesity and coronary artery disease. These diseases differ from the group listed in the paragraph above in that more than one gene is associated with the disease. This creates a more complex scenario for the gene "therapist. …