Gene therapy

Definition

Gene therapy involves altering the genes inside your body's cells to stop disease. Genes contain your DNA — the code that controls much of your body's form and function. Your cells use the information from your genes to manufacture proteins that do the work in your body, from making you grow taller to regulating your body systems. Throughout your life, your genes turn on and off as needed to control cell activity.

Genes that don't work properly can cause disease. Gene therapy replaces a faulty gene or adds a new gene in an attempt to cure disease or make changes in your body so that it's better able to combat disease. Gene therapy holds promise for treating a wide range of diseases, including cancer, cystic fibrosis, heart disease, diabetes, hemophilia and AIDS.

Researchers are still learning about how gene therapy works and the best way to administer gene therapy. Currently, in the United States, gene therapy is available only as part of a clinical trial.

Why it's done

Gene therapy is used to correct defective genes in order to cure a disease or to help your body better fight disease. Researchers are investigating several ways to do this, including:

• Replacing missing or mutated genes. This is currently the most common gene therapy approach. Some cells become diseased because certain genes have been permanently turned off. Other cells may be missing certain genes. Researchers hope that replacing missing or defective genes can help treat certain diseases. For instance, a common tumor suppressor gene called p53 normally prevents tumor growth in your body. Several types of cancer have been linked to a missing or inactive p53 gene. If doctors could replace p53 where it's missing, that might trigger the cancer cells to die.
• Changing the regulation of a gene. Mutated genes that cause disease could be turned off so that they no longer promote disease, or healthy genes that help prevent disease could be turned on so that they can inhibit the disease.
• Making diseased cells more evident to the immune system. In some cases, your immune system doesn't attack diseased cells because it doesn't recognize them as intruders. Using gene therapy, doctors could potentially infuse mutated cells with genes that make them more recognizable to your immune system. Or enhancements could be made to immune cells to make it easier for them to recognize mutated cells that are a threat.

Risks

Gene therapy poses a number of risks. First, the way the genes are delivered can be problematic. A gene can't easily be inserted directly into your cells. Rather, it usually has to be delivered using a carrier, called a vector. The most common gene therapy vectors are viruses because they can recognize certain cells and carry genetic material into the cells' genes. Researchers are trying to take advantage of this unique capability by removing the original disease-causing genes from the viruses, replacing them with the genes needed to stop disease, and then inserting the altered viruses into a person's diseased cells, where they can deliver their genetic material.

This technique presents the following risks:

• Immune response. Your body's immune system may see the newly introduced viruses as intruders and attack them. This may cause inflammation, toxicity and, in severe cases, organ failure.
• Viral spread. Because viruses can affect more than one type of cells, it's possible that the viral vectors may infect cells in addition to the ones for which they were intended — just those containing mutated or missing genes. If this happens, healthy cells may be damaged, causing other illness or diseases, including cancer.
• Reversion of the virus to its original form. It's possible that once introduced into the body, the viruses may recover their original ability to cause disease.
• Possibility of inducing a tumor. If the new genes get inserted in the wrong spot in the genome, there is a chance that the insertion might lead to tumor formation. This has occurred occasionally in some clinical trials.

Another risk of gene therapy is that the new DNA introduced into your body may affect your reproductive cells — egg cells in women, sperm cells in men. This could result in genetic changes that could affect children you have after treatment.

The gene therapy clinical trials under way in the U.S. are closely monitored by the Food and Drug Administration and the National Institutes of Health to ensure the safety of those who participate in the studies.

What you can expect

Currently, the only way for you to receive gene therapy is to participate in a clinical trial. These studies help doctors determine whether a gene therapy approach is safe for people. They also demonstrate the effects of gene therapy on the body. For instance, doctors may analyze samples of cells from people in a gene therapy clinical trial to look for signs that the makeup of diseased cells is changing. They might also look to see how the immune system reacts to the gene therapy.

Your specific procedure will depend on the disease you have and the type of gene therapy being used. For example, in some clinical trials, you may have blood drawn, or you may need a bone marrow aspiration — a procedure in which a liquid sample of your bone marrow is withdrawn — or a bone marrow biopsy — a procedure in which a sample of solid marrow material is taken. Then, in a laboratory, cells from the blood or bone marrow are exposed to a virus or another type of vector that contains the desired genetic material. Once the vector has entered the cells in the laboratory, those cells are then injected back into your body through a vein. In other research studies, the vector is injected or given intravenously (IV) into tissue in the body, where the cells take up the vector along with the altered genes.

Viruses aren't the only vectors that can be used to carry altered genes into your body's cells. Other vectors sometimes used in clinical trials include:

• Stem cells. Stem cells are the raw material cells of your body — cells from which all other cells in your body with specialized functions are created. For gene therapy, stem cells can be altered in a laboratory to accept new genes that can help fight disease.
• Liposomes. These fatty particles have the ability to carry the new, therapeutic genes to the target cells and pass the genes into your cells' DNA.

Results

The possibilities of gene therapy hold much promise. To date, however, that promise has not been realized. Some clinical trials have recorded small successes for a few participants. But, several significant barriers stand in the way of gene therapy becoming a reliable form of treatment. The barriers include developing reliable vectors, consistently ensuring safety, targeting the correct cells, and preventing genetic changes from being passed on from parents to children.

Although at this time no clinical trial has been seen as a breakthrough in overcoming all these barriers, gene therapy is a very active area of research. Researchers hope that with continued study, advances in gene therapy will eventually make it a practical approach to treating disease.