Gene Therapy

Overview

Your DNA contains instructions for making proteins, which perform countless functions throughout the body. Sometimes, changes in DNA, called mutations, cause proteins to stop working or not be made in the first place. These changes can cause inherited disorders such as cystic fibrosis, retinal degeneration, thalassemia, hemophilia, sickle cell disease, and certain kinds of hearing loss.

Gene therapies involve altering DNA or providing new DNA to correct these problems. Scientists are developing gene therapies to prevent and treat several diseases. Gene therapies currently approved by the U.S. Food and Drug Administration (FDA) include treatments for sickle cell disease, a rare inherited eye condition and certain types of cancer.

Related Terms: Gene therapy is also known by these related terms:

• Genetic therapy
• Gene transfer
• Gene addition
• Genome editing

Gene Therapy Approaches

Gene Transfer 

Gene transfer introduces genetic materials into specific cells. This may stay in the cell as an extra piece of DNA or be inserted into the cell’s chromosomes to become part of the cell’s own DNA.

In gene transfer, a molecular package called a vector carries the gene into the cell. Vectors are often created from harmless viruses. Once the gene is inside the cell’s nucleus — the central part of the cell where DNA is packaged in chromosomes — the cell starts to make the critical protein needed for the cell to work properly.

Genome Editing

Genome editing is a newer approach that allows precise correction or other targeted changes to the DNA in cells. This technique can remove a stretch of DNA that causes a disease, correct a mutated gene, turn off a gene to prevent it from making a harmful protein, or turn on or boost the activity of a needed gene.

Genome editing introduces a set of components that work together into cells. One is a protein that cuts DNA, like a pair of molecular scissors. Another is a guide molecule that sticks 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. A piece of normal DNA can also be introduced as a third component. This corrected version of the faulty DNA is used to rebuild the DNA correctly after it is cut.

A genome editing tool called CRISPR, developed in 2009, has made it easier than ever to edit DNA. CRISPR is simpler, faster, cheaper, and more accurate than older genome editing methods. Many scientists who perform genome editing now use CRISPR-based technologies (including its newer version, called prime editing).

Gene therapies can target two categories of cells:

• Somatic gene therapies target non-reproductive cells. Changes made in these cells affect only the person who receives the gene therapy.
• Germline gene therapies change DNA in reproductive cells, like sperm and eggs. Changes to the DNA of reproductive cells are passed down from generation to generation. Scientists approach germline therapy research with caution because edits to a germline cell would be passed down through generations and could have unanticipated effects. To prevent germline edits from affecting future generations, almost all countries, including the U.S., and many organizations prohibit and have strict regulations to prevent germline editing. NIH does not perform or fund studies on germline gene therapies.

Even though CRISPR improved upon older genome editing technologies, it is not perfect. Sometimes, genome editing tools cut in the wrong spot, and scientists are not yet sure how these errors might affect patients. Assessing the safety of gene therapies and improving upon genome editing technologies are critical steps to ensure that this technology is ready for use in patients.

Related Health Effects

Gene therapies hold promise to treat many diseases, but they are still new approaches to treatment and may have risks. These include inducing certain types of cancer, allergic reactions, or damage to organs or tissues if an injection is involved.

Recent advances have made gene therapies much safer. This 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, and researchers are still studying the risks.

Using Gene Therapy for Treatment

The method of gene transfer or genome editing treatment used depends on the condition and what organ or types of cells need to be treated. In some treatments, your cells can be collected, treated outside of the body, and then returned. Other treatments directly modify the cells in your body.

For blood and immune conditions, a doctor may take blood from your veins or bone marrow from your hip bone to be modified in a laboratory. Blood and bone marrow contain hematopoietic stem cells, which produce key cells that make up the blood and immune system. Scientists may use either gene transfer or genome editing to alter the stem cells. The modified cells are returned to your body through an IV line in one of your blood vessels.

Some gene therapies require altering cells in organs or tissues that cannot be easily removed from the patient. Researchers are still working on ways to deliver genetic therapy into the affected tissues. Methods being studied include IV infusion into the bloodstream and injection directly into specific organs.

Several gene therapies are currently approved by the FDA.

Researchers have also been using gene therapy to treat rare disorders in infants and children. For example, children born with a rare genetic disorder called severe combined immunodeficiency (SCID) received gene therapy to restore immune system function. Gene therapy delivered into the brain was used to treat a rare, debilitating neurological disorder called aromatic L-amino acid decarboxylase (AADC). Other researchers designed a personalized gene-editing approach to mend a faulty gene in a baby born with a rare, often deadly disorder called carbamoyl-phosphate synthetase 1 (CPS1) deficiency.

Find Clinical Trials

Clinical trials uncover better ways to prevent, diagnose, treat, and understand diseases and conditions. To ensure results apply to everyone, volunteers of all ages, sexes, and backgrounds, including both healthy individuals and those with specific medical conditions, are needed. Find clinical trials on gene therapy.

Research Information

The National Institutes of Health (NIH) is the largest public funder of biomedical research in the world. NIH invests most of its budget in medical research seeking to enhance life and to reduce illness and disability. NIH-funded research has led to breakthroughs and new treatments helping people live longer, healthier lives, and building the research foundation that drives discovery.

Gene therapies are still in the early stages of research, development, and clinical trials. Scientists are still working on ways to deliver genetic therapy for conditions where cells cannot be easily removed from the patient for treatment in the laboratory.

Scientists are also using genome editing in the laboratory to investigate different diseases that affect humans. They edit the genomes of animals, like mice and zebrafish, because animals share many of the same genes as humans. For example, mice and humans share about 85% of their genes. By changing genes in a mouse, scientists can observe how these changes affect the mouse’s health. This gives them insights into how similar changes in human genomes might affect human health. Gene editing in mouse models of human disease can also provide a direct pathway to clinical trials.

NIH scientists have been deleting different genes in zebrafish one at a time using CRISPR to see how the deletions impact the fish. One lab focuses on zebrafish genes similar to the genes that cause human deafness, to better understand the genomic basis of deafness.

To develop future targets for gene therapy for retinal degenerations, NIH scientists have been using stem cell-based models. These allow development of patient-specific eye tissue in a dish to test gene therapies for their ability to rescue the structure and function of the eye.

To develop future targets for gene therapy for hearing loss, scientists have been investigating genes and proteins in the inner ear. NIH-supported research has led to the identification of many genes that can cause hearing loss when mutated or missing. To date, more than 150 such genes have been identified.

Find NIH-funded research projects using NIH RePORTER, a searchable database of current and past research projects supported by NIH and other federal agencies.