Gene therapy is a medical approach that treats or prevents disease by correcting the underlying genetic problem. Gene therapy techniques allow doctors to treat a disorder by altering a person’s genetic makeup instead of using drugs or surgery.
The earliest method of gene therapy, often called gene transfer or gene addition, was developed to:
- Introduce a new gene into cells to help fight a disease.
- Introduce a non-faulty copy of a gene to stand in for the altered copy causing disease.
Later studies led to advances in gene therapy techniques. A newer technique, called genome editing (an example of which is CRISPR-Cas9), uses a different approach to correct genetic differences. Instead of introducing new genetic material into cells, genome editing introduces molecular tools to change the existing DNA in the cell. Genome editing is being studied to:
- Fix a genetic alteration underlying a disorder, so the gene can function properly.
- Turn on a gene to help fight a disease.
- Turn off a gene that is functioning improperly.
- Remove a piece of DNA that is impairing gene function and causing disease.
Gene therapies are being used to treat a small number of diseases, including an eye disorder called Leber congenital amaurosis and a muscle disorder called spinal muscular atrophy. Many more gene therapies are undergoing research to make sure that they will be safe and effective. Genome editing is a promising technique also under study that doctors hope to use soon to treat disorders in people.
Gene therapy involves altering the genes inside your body’s cells in an effort to treat or stop disease.
Genes contain your DNA — the code that controls much of your body’s form and function, from making you grow taller to regulating your body systems. 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 improve your body’s ability to fight disease. Gene therapy holds promise for treating a wide range of diseases, such as cancer, cystic fibrosis, heart disease, diabetes, hemophilia and AIDS.
Researchers are still studying how and when to use 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 help your body better fight disease.
Researchers are investigating several ways to do this, including:
- Replacing mutated genes. Some cells become diseased because certain genes work incorrectly or no longer work at all. Replacing the defective genes may help treat certain diseases. For instance, a gene called p53 normally prevents tumor growth. Several types of cancer have been linked to problems with the p53 gene. If doctors could replace the defective p53 gene, that might trigger the cancer cells to die.
- Fixing mutated genes. 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 could 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. Doctors could use gene therapy to train your immune system to recognize the cells that are a threat.
Gene therapy has some potential risks. 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 remove the original disease-causing genes from the viruses, replacing them with the genes needed to stop disease.
This technique presents the following risks:
- Unwanted immune system reaction. Your body’s immune system may see the newly introduced viruses as intruders and attack them. This may cause inflammation and, in severe cases, organ failure.
- Targeting the wrong cells. Because viruses can affect more than one type of cells, it’s possible that the altered viruses may infect additional cells — not just the targeted cells containing mutated genes. If this happens, healthy cells may be damaged, causing other illness or diseases, such as cancer.
- Infection caused by the virus. It’s possible that once introduced into the body, the viruses may recover their original ability to cause disease.
- Possibility of causing a tumor. If the new genes get inserted in the wrong spot in your DNA, there is a chance that the insertion might lead to tumor formation.
The gene therapy clinical trials underway in the U.S. are closely monitored by the Food and Drug Administration and the National Institutes of Health to ensure that patient safety issues are a top priority during research.
What you can expect
Currently, the only way for you to receive gene therapy is to participate in a clinical trial. Clinical trials are research studies that help doctors determine whether a gene therapy approach is safe for people. They also help doctors understand the effects of gene therapy on the body.
Your specific procedure 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 need 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, where your 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 being studied in clinical trials include:
- Stem cells. Stem cells are the cells from which all other cells in your body are created. For gene therapy, stem cells can be trained in a lab to become cells 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.
The possibilities of gene therapy hold much promise. Clinical trials of gene therapy in people have shown some success in treating certain diseases, such as:
- Severe combined immune deficiency
- Blindness caused by retinitis pigmentosa
But several significant barriers stand in the way of gene therapy becoming a reliable form of treatment, including:
- Finding a reliable way to get genetic material into cells
- Targeting the correct cells
- Reducing the risk of side effects
Gene therapy continues to be a very important and active area of research aimed at developing new, effective treatments for a variety of diseases.
Explore Mayo Clinic studies of tests and procedures to help prevent, detect, treat or manage conditions.
Gene therapy works by altering the genetic code to recover the functions of critical proteins. Proteins are the workhorses of the cell and the structural basis of the body’s tissues. The instructions for making proteins are carried in a person’s genetic code, and variants (or mutations) in this code can impact the production or function of proteins that may be critical to how the body works. Fixing or compensating for disease-causing genetic changes may recover the role of these important proteins and allow the body to function as expected.
Gene therapy can compensate for genetic alterations in a couple different ways.
- Gene transfer therapy introduces new genetic material into cells. If an altered gene causes a necessary protein to be faulty or missing, gene transfer therapy can introduce a normal copy of the gene to recover the function of the protein. Alternatively, the therapy can introduce a different gene that provides instructions for a protein that helps the cell function normally, despite the genetic alteration.
- Genome editing is a newer technique that may potentially be used for gene therapy. Instead of adding new genetic material, genome editing introduces gene-editing tools that can change the existing DNA in the cell. Genome editing technologies allow genetic material to be added, removed, or altered at precise locations in the genome. CRISPR-Cas9 is a well-known type of genome editing.
Genetic material or gene-editing tools that are inserted directly into a cell usually do not function. Instead, a carrier called a vector is genetically engineered to carry and deliver the material. Certain viruses are used as vectors because they can deliver the material by infecting the cell. The viruses are modified so they can’t cause disease when used in people. Some types of virus, such as retroviruses, integrate their genetic material (including the new gene) into a chromosome in the human cell. Other viruses, such as adenoviruses, introduce their DNA into the nucleus of the cell, but the DNA is not integrated into a chromosome. Viruses can also deliver the gene-editing tools to the nucleus of the cell.
The vector can be injected or given intravenously (by IV) directly into a specific tissue in the body, where it is taken up by individual cells. Alternately, a sample of the patient’s cells can be removed and exposed to the vector in a laboratory setting. The cells containing the vector are then returned to the patient. If the treatment is successful, the new gene delivered by the vector will make a functioning protein or the editing molecules will correct a DNA error and restore protein function.
Gene therapy with viral vectors has been successful, but it does carry some risk. Sometimes the virus triggers a dangerous immune response. In addition, vectors that integrate the genetic material into a chromosome can cause errors that lead to cancer. Researchers are developing newer technologies that can deliver genetic material or gene-editing tools without using viruses. One such technique uses special structures called nanoparticles as vectors to deliver the genetic material or gene-editing components into cells. Nanoparticles are incredibly small structures that have been developed for many uses. For gene therapy, these tiny particles are designed with specific characteristics to target them to particular cell types. Nanoparticles are less likely to cause immune reactions than viral vectors, and they are easier to design and modify for specific purposes.
Researchers continue to work to overcome the many technical challenges of gene therapy. For example, scientists are finding better ways to deliver genes or gene-editing tools and target them to particular cells. They are also working to more precisely control when the treatment is functional in the body.
Scientific journal articles for further reading
Bulcha JT, Wang Y, Ma H, Tai PWL, Gao G. Viral vector platforms within the gene therapy landscape. Signal Transduct Target Ther. 2021 Feb 8;6(1):53. doi: 10.1038/s41392-021-00487-6. PMID: 33558455. Free full-text article from PubMed Central: PMC7868676.
Duan L, Ouyang K, Xu X, Xu L, Wen C, Zhou X, Qin Z, Xu Z, Sun W, Liang Y. Nanoparticle Delivery of CRISPR/Cas9 for Genome Editing. Front Genet. 2021 May 12;12:673286. doi: 10.3389/fgene.2021.673286. PubMed: 34054927. Free full-text article from PubMed Central: PMC8149999.
Credit: U.S. National Library of Medicine