Our bodies are made up of cells, and inside each cell is the DNA that we inherit from our parents. Genes are short sections of our DNA that act as blueprints for making the proteins our body needs to function. Proteins are molecules that do most of the work in cells — everything from determining the color of our eyes to coordinating biological reactions and from supporting tissue structure to protecting us from disease. Sometimes a gene is defective and gives faulty instructions to the body’s cells, which can result in disease.
In vivo gene therapy strives to cure or improve the child’s disease using genetic material to alter the disease-causing gene. This can happen by:
- Replacing a faulty or disease-causing gene with a healthy copy of the gene
- Deactivating a defective gene that causes disease or activating a gene because it isn’t functioning
- Introducing a new or modified gene to treat a disease
Scientists identify and select genes that have disease-fighting or function-restoring properties.
To get the new gene into the child’s cells, most gene therapies use an engineered tool called a viral vector, which carries the gene to where it needs to go inside the cell. Viruses are used because they’re good at getting into cells. Viral vectors are safe because they have the infection-causing genes removed before they’re used in gene therapy.
Once the new, corrected gene is in the child’s cells, it takes the place of the nonworking or defective gene, with the goal of stopping the disease or making it less severe.
What is the difference between in vivo gene therapy and ex vivo gene therapy?
Gene therapy can be introduced into the child’s body in two different ways. It can be directly infused into them (which is called in vivo gene therapy), or it can be used to modify cells in a lab that will then be transplanted into the child (called ex vivo gene therapy).
With in vivo gene therapy, corrected genes are given directly to the patient. This can occur through an IV or through local delivery to a specific organ, like the eye. This is called “in vivo” gene therapy because the new gene is introduced to the patient’s cells inside the body via a viral vector.
In ex vivo gene therapy, a patient’s cells are taken out of their body and new genes are introduced to those cells in a lab using gene therapy. The modified cells are then transplanted back into the patient to fight disease or correct nonfunctioning genes. This is called “ex vivo” gene therapy because the new gene is introduced to the patient’s cells outside the body.
How does in vivo gene therapy work?
When in vivo gene therapy is infused into the child’s body, the viral vector carries the new gene to the cells that make up the organs that are affected by the genetic disease. The cells will then make therapeutic levels of the new protein to improve the genetic disease.
An example of in vivo gene therapy is Luxturna®, which treats a rare type of inherited blindness. Luxturna® is given directly into the eye, and the viral vector delivers the gene therapy into the cells that make up the retina. Another example of in vivo gene therapy is Elevidys®, which treats Duchenne muscular dystrophy. Elevidys is given through an IV, and the viral vector delivers the gene therapy to muscle cells.
Gene therapy is regulated by the Food and Drug Administration (FDA). The FDA must approve any clinical trial and then closely review the results before approving any gene therapy for use in children.
The future of in vivo gene therapy
Potential future applications of in vivo gene therapy go beyond disorders of the eye, blood or nervous systems to treat other diseases caused by a genetic defect. Researchers are working to develop therapies to treat metabolic disorders (like Sanfilippo syndrome), muscular deficiencies, lysosomal storage diseases and others. Learn more about CHOP’s in vivo gene therapy efforts.