Genetic therapies aim to treat or cure conditions by correcting problems in your DNA. Your DNA, including specific genes, contains instructions for making proteins that are essential for good health. Mutations, or changes in your DNA, can lead to proteins that do not work properly or that are missing altogether. These changes can cause genetic disorders such as cystic fibrosis, alpha-1 antitrypsin deficiency, thalassemia, hemophilia, and sickle cell disease.
Watch this video for a quick introduction to genetic therapies. Medical Animation Copyright © 2020 Nucleus Medical Media, All rights reserved.
Genetic therapies are approaches that treat genetic disorders by providing new DNA to certain cells or correcting the DNA. Gene transfer approaches, also called gene addition, restore the missing function of a faulty or missing gene by adding a new gene to affected cells. The new gene may be a normal version of the faulty gene or a different gene that bypasses the problem and improves the way the cell works.
Genome editing is a newer approach that allows precise correction or other targeted changes to the DNA in cells to restore a cell’s function. Genome editing can do the following:
Gene transfer or genome editing treatments can directly modify the cells in your body, or your cells can be collected and treated outside of your body and then returned to you. For example, a doctor can remove immune system cells or bone marrow cells from your body, modify their DNA, and then re-introduce the cells to your body.
The only genetic therapies that are currently approved by the U.S. Food and Drug Administration (FDA) are for a rare inherited eye condition, as well as certain types of cancer. Genetic therapies that are in development could treat or cure other inherited disorders; treat other cancers; or treat infections, including HIV.
Explore this Health Topic to learn more about genetic therapies, our role in research and clinical trials to improve health, and where to find more information.
Genetic therapies may use gene transfer or genome editing approaches to change the DNA in a patient’s cells to treat a condition.
Gene transfer introduces an additional gene into specific cells. This gene may stay as an extra piece of DNA in the cell or be inserted into the cell’s own chromosomes and thus become part of the cell’s own DNA.
A molecular package called a vector carries the gene to the cell nucleus, which is the central part of the cell where DNA is packaged in chromosomes. Vectors are created in the laboratory, often from viruses that have been modified to remove viral genes that cause disease and to carry a treatment gene.
Once the gene is inside the nucleus, the cell will start to make the critical protein needed for the cell to work properly. The new proteins make up for missing or faulty proteins and are meant to improve health for people who receive genetic therapies.
Watch this video to learn about how genome editing works. Medical Animation Copyright © 2020 Nucleus Medical Media, All rights reserved.
Genome editing introduces components that function together into cells. One component is a protein that cuts DNA, similar to a pair of molecular scissors. Another component is a guide molecule that can stick to DNA at specific sites. When the guide molecule sticks to an area of faulty DNA, the scissors protein attaches to the guide molecule, and cuts out the faulty DNA.
After the target DNA is cut, several things can happen. The cell may leave behind a gap, return the DNA to its original state, or fill in this gap with the corrected DNA. The cell can fill in the corrected DNA if it has a template DNA to direct the cell to rebuild a healthier version of the DNA that was removed. Therefore, sometimes a small piece of template DNA is introduced as a third component. This DNA is a corrected version of the faulty DNA, and it is used to rebuild the DNA correctly after it is cut open.
In the future, genetic therapies may be used to prevent, treat, or cure certain inherited disorders, such as cystic fibrosis, alpha-1 antitrypsin deficiency, hemophilia, beta thalassemia, and sickle cell disease. They also may be used to treat cancers or infections, including HIV.
Genetic therapies that are currently approved by the FDA are available for people who have Leber congenital amaurosis, a rare inherited condition that leads to blindness. CAR T-cell therapy is FDA approved for people who have blood cancers, such as acute lymphoblastic leukemia (ALL) and diffuse large B-cell lymphoma.
Genetic therapies are still in the early stages of research, development, and clinical trials, but researchers already know a lot about how they may work as a treatment. For example, if you participate in a clinical trial or receive genetic therapy in the future, treatment may be provided in one of two ways. Your cells may be directly modified inside your body, or your cells may be collected and modified outside your body and then returned to you. The method may depend on your condition and what organ or types of cells in your body need to be treated.
If you have a blood or immune condition, the doctor may take blood from your veins or bone marrow from your hip bone to be modified in a laboratory with genetic therapy. Blood and bone marrow contain hematopoietic stem cells, which produce other key cells that make up the blood and immune system.
In the laboratory, scientists may use either gene transfer or genome editing to change the sample of stem cells provided by you. The modified cells are returned to your body through an intravenous (IV) line in one of your blood vessels. This procedure is called cell-based therapy or a blood and bone marrow transplant. The altered hematopoietic stem cells will produce healthy blood or immune cells.
Genetic therapies for sickle cell disease are examples of how this approach is being developed. Currently, a blood and bone marrow transplant of stem cells from a relative or an unrelated well-matched donor can cure sickle cell disease, but many patients do not have a well-matched donor available. Genetic therapies that modify a person’s own hematopoietic stem cells may provide a cure for people who do not have a well-matched donor. Modified hematopoietic stem cells can be injected into the blood, then the cells travel in the bloodstream to the marrow spaces inside the bones. Once inside the bone marrow, the cells can produce healthy red blood cells that do not sickle. Watch the video below to learn more about how genome editing is being tested for sickle cell disease.
This animation discusses how genome editing may be used to treat or cure sickle cell disease. Medical Animation Copyright © 2020 Nucleus Medical Media, All rights reserved.
Sometimes, genetic therapies are needed to alter cells that cannot be easily removed from the patient for treatment in the laboratory. Researchers are still working on ways to deliver the genetic therapy for these conditions. The methods being studied include IV infusion into the bloodstream, injection directly into an organ, and other ways to directly deliver the therapy into the affected tissues.
One condition that could be treated this way is hemophilia B. Hemophilia is caused by a faulty gene that prevents production of a protein necessary to clot the blood after an injury. Genetic therapy that is being developed for Hemophilia B involves infusing a vector carrying the normal clotting factor gene into the bloodstream. The vector then reaches liver cells to produce the clotting factor needed for better health.
Genetic therapies hold promise to treat many diseases, but they are still new approaches to treatment and may have risks. Potential risks could include certain types of cancer, allergic reactions, or damage to organs or tissues if an injection is involved.
Recent advances have made genetic therapies much safer. Better safety has resulted in the FDA approving some gene transfer therapies for clinical use in the United States. There have been a few clinical studies on genome editing, but the approach is much newer than gene transfer. Researchers are still studying the risks.
The National Institutes of Health, which includes the NHLBI, does not perform or fund studies on genome editing targeting sperm, eggs, or embryos in humans. These changes would be passed on to the patient’s children and could have unanticipated effects.
Learn about some of the ways we continue to translate current research into improved health for people using genetic therapies. Research on this topic is part of the NHLBI’s broader commitment to advancing blood disorders and blood safety scientific discovery.
In support of our mission, we are committed to advancing research on genetic therapies in part through the following ways.
Learn about other exciting ways we are advancing research to improve lives.
We lead or sponsor many studies relevant to genetic therapies using gene transfer or genome editing. See whether you or someone you know is eligible to participate in our clinical trials.
After reading our Genetic Therapies Health Topic, you may be interested in additional information found in the following resources.