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, or inherited, disorders such as cystic fibrosis, thalassemia, hemophilia, and sickle cell disease.
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:
- Remove a stretch of DNA that causes a disease
- Turn off a gene to prevent it from making a harmful protein
- Turn on a gene or instruct a cell to make more of a needed protein
- Correct a mutated gene
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, cells that are part of your body’s natural defense system, or bone marrow cells from your body, modify their DNA, and then re-introduce them to your body.
Gene transfer: 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 to become part of the cell’s own DNA.
A molecular package called a vector carries the gene to the cell nucleus, 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.
Genome editing: Genome editing introduces components that work 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.
Benefits and Risks
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 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.