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Overview

Genes contain DNA — the code that controls much of the body's form and function. DNA controls everything from hair color and height to breathing, walking and digesting food. Genes that don't work properly can cause disease. Sometimes these genes are called mutations.

Gene therapy aims to fix a faulty gene or replace it with a healthy gene to try to cure disease or make the body better able to fight disease. It holds promise as a treatment for a wide range of diseases, such as cancer, cystic fibrosis, heart disease, diabetes, hemophilia and AIDS.

The U.S. Food and Drug Administration (FDA) has approved gene therapy products for several conditions, including cancer, spinal muscular atrophy, hemophilia and sickle cell disease. But for most people, gene therapy is available only as part of a clinical trial.

Clinical trials are research studies that help healthcare professionals find out whether a gene therapy approach is safe for people. Clinical trials also help healthcare professionals learn how gene therapy affects the body.

Why it's done

Gene therapy is done to:

• Fix genes that don't work properly. Faulty 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 could stop the disease.
• Replace genes that don't work properly. Some cells become diseased because certain genes don't work properly or no longer work at all. Replacing these genes with healthy genes may help treat certain diseases. For example, a gene called p53 usually prevents tumor growth. Several types of cancer have been linked to problems with the p53 gene. If healthcare professionals could replace the faulty p53 gene, the healthy gene might cause the cancer cells to die.
• Make the immune system aware of diseased cells. In some cases, your immune system doesn't attack diseased cells because it doesn't see them as intruders. Healthcare professionals could use gene therapy to train your immune system to see these cells as a threat.

Risks

Gene therapy has some potential risks. A gene can't easily be inserted directly into your cells. Rather, it usually is delivered using a carrier called a vector.

The most common gene therapy vectors are viruses. That's because they can recognize certain cells and carry genetic material into the genes of those cells. Researchers change the viruses, replacing genes that cause disease with genes needed to stop disease.

This technique presents risks, including:

• Unwanted immune system reaction. Your body's immune system may see the newly introduced viruses as intruders. As a result, it may attack them. This may cause a reaction that ranges from swelling to organ failure.
• Targeting the wrong cells. Viruses can affect more than one type of cell. So it's possible that the changed viruses may get into cells beyond those that aren't working properly. The risk of damage to healthy cells depends on which type of gene therapy is used and what it's used for.
• Infection caused by the virus. It's possible that once the viruses get into the body, they may once again be able to cause disease.
• Possibility of causing errors in your genes. These errors can lead to cancer.

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

• Stem cells. All cells in your body are created from stem cells. For gene therapy, stem cells can be altered or corrected in a lab to become cells to fight disease.
• Liposomes. These particles can carry the new, therapeutic genes to the target cells and pass the genes into the DNA of your cells.

The FDA and the National Institutes of Health are closely watching the gene therapy clinical trials underway in the U.S. They are making sure patient safety issues are a top priority during research.

What you can expect

Which procedure you have will depend on the disease you have and the type of gene therapy being used. For example, in one type of gene therapy:

• You may have blood drawn or you may have bone marrow removed from your hipbone with a large needle.
• Then, in a lab, 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 lab, those cells are injected back into your body into a vein or into tissue. Then your cells take up the vector along with the changed genes.

In another type of gene therapy, a viral vector is infused directly into the blood or into a selected organ. Talk with your healthcare team to find out what type of gene therapy would be used and what you can expect.

Results

Gene therapy is a promising treatment and a growing area of research. But its clinical use is limited today.

In the U.S., FDA-approved gene therapy products include:

• Axicabtagene ciloleucel (Yescarta). This gene therapy is for adults who have certain types of large B-cell lymphoma that don't respond to treatment.
• Onasemnogene abeparvovec-xioi (Zolgensma). This gene therapy can be used to treat children under age 2 who have spinal muscular atrophy.
• Talimogene laherparepvec (Imlygic). This gene therapy is used to treat certain types of tumors in people with melanoma that come back after surgery.
• Tisagenlecleucel (Kymriah). This gene therapy is for people up to 25 years old who have follicular lymphoma that has come back or isn't responding to treatment.
• Voretigene neparvovec-rzyl (Luxturna). This gene therapy is for people 1 year old and older who have a rare inherited type of vision loss that can lead to blindness.
• Exagamglogene autotemcel (Casgevy). This gene therapy is for treating people 12 years and older with sickle cell disease or beta thalassemia who meet certain criteria.
• Delandistrogene moxeparvovec-rokl (Elevidys). This gene therapy is for children ages 4 through 5 years who have Duchenne muscular dystrophy and a flawed DMD gene.
• Lovotibeglogene autotemcel (Lyfgenia). This gene therapy is for people 12 years and older with sickle cell disease who meet certain criteria.
• Valoctocogene roxaparvovec-rvox (Roctavian). This gene therapy is for adults with severe hemophilia A who meet certain criteria.
• Beremagene geperpavec-svdt (Vyjuvek). This is a topical gene therapy for treating wounds in people 6 months and older who have dystrophic epidermolysis bullosa, a rare inherited condition that causes fragile, blistering skin.
• Betibeglogene autotemcel (Zynteglo). This gene therapy is for people with beta thalassemia who need regular transfusions of red blood cells.

Clinical trials of gene therapy in people have helped treat several diseases and disorders, including:

• Severe combined immunodeficiency.
• Hemophilia and other blood disorders.
• Blindness caused by retinitis pigmentosa.
• Leukemia.
• Inherited neurological disorders.
• Cancer.
• Heart and blood vessel diseases.
• Infectious diseases.

But several major barriers stand in the way of some types of gene therapy becoming a reliable form of treatment, including:

• Finding a reliable way to get genetic material into cells.
• Targeting the correct cells or gene.
• Lowering the risk of side effects.

Cost and insurance coverage also can be a major barrier to treatment.

Although the number of gene therapy products on the market is limited, gene therapy research continues to seek new, effective treatments for various diseases.