What Is In Vivo Gene Therapy?
Reviewed by Jennifer Harding, MPA Sarah McCague, MS Juliana Small, PhD
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.
-
Narrator: Our team at Children's Hospital of Philadelphia wants to help you understand in vivo gene therapy. But before we can get into what in vivo means, we should start by explaining what is gene therapy? Gene therapy is a way to treat or prevent disease by using genetic material like DNA. First, the basics.
Our bodies are made up of cells. And inside each cell is its DNA. DNA is divided into short sections called genes. Genes act as instruction manuals, telling our cells how to make proteins. Proteins are necessary for our bodies to function. Proteins do important work like helping us digest food and helping our blood clot when we get a cut.
But sometimes, a gene's instructions for making a protein are not correct. This can cause changes in how a protein works. These incorrect instructions can result in a genetic disease. Gene therapy can deliver new instructions to the body to make proteins that function correctly.
Hannah: I was going blind. After I received a healthy gene to replace the bad gene in my eyes, I was able to see so much better.
Narrator: How does gene therapy work? There are two types of gene therapy. Ex vivo and in vivo. Ex vivo means outside the body. When a child receives ex vivo gene therapy, it means their cells are removed from their body, treated with gene therapy, and then put back into their body. In vivo means inside the body.
Let's talk more about how in vivo gene therapy works. When a child receives in vivo gene therapy, we use something called a vector, which acts like a delivery truck. Vectors with the new or corrected gene can get into the body through an iv, or doctors can put them in a specific spot, like the eye. The vector then travels to the cells where the corrected gene is needed.
With the help of the new gene, the cells start making the proper kind of protein. One condition that can be treated with an in vivo gene therapy, is spinal muscular atrophy, which is a nerve disease that used to be fatal for children with a severe type. Children with a disease now can receive an in vivo gene therapy that stops the progression of the condition.
William: Because of spinal muscular atrophy, I couldn't even roll over after gene therapy. I can now stand and take steps.
Narrator: Gene therapy is changing and saving children's lives and CHOP has been at the forefront of gene therapy breakthroughs from the start. CHOP was the first in the world to use in vivo gene therapy delivered into the bloodstream, which is the most commonly used method today.
And we've pioneered many other groundbreaking discoveries. Our determined researchers are exploring the use of in vivo gene therapy for all kinds of diseases so that more children worldwide will have bright futures.
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.