Gene Therapy: What to Expect

What is gene therapy?

Genes come from our parents and influence everything from our hair color and height to how likely we are to develop certain diseases. Genes also help build and maintain our cells by providing instructions for building proteins. Sometimes, genes have a mutation—a change—that impacts how these proteins are built. Mutations can be passed down from our parents or happen randomly. If the mutation causes disease, gene therapy may be able to help.

Gene therapy aims to restore a protein’s normal abilities. There are several ways to accomplish this, including introducing a new or changed copy of a gene, turning genes on or off, and replacing the part of the gene that is causing disease with a normal part.

There are many applications of gene therapy. When it is used to treat inherited disorders (disease-causing genetic mutations present when a person is born), there are two big categories: cell-based (ex vivo) and tissue targeted (in vivo).

Clinic visits

During clinic visits before therapy begins, screening tests are performed to see if you or your child is eligible for gene therapy. Screening tests and procedures may include:

• Questions about medical history.
• A physical exam.
• Blood tests.
• Imaging studies such as magnetic resonance imaging (MRI), computed tomography (CT) scans, and ultrasounds.
• An electrocardiogram (ECG), which measures the heart’s electrical activity, and echocardiogram (ECHO), which measures how blood moves through the heart.
• Pulmonary function testing (PFT), which measures lung capacity and function.

You or your child may meet the following members of our care team:

• A doctor who specializes in stem cell transplantation. These doctors are experts in the detailed process where your child’s stem cells will be collected and edited as part of the treatment.
• A doctor who specializes in treating your child’s condition. For example, if your child has thalassemia, you will meet with a pediatric hematologist.

Gene therapy process: cell-based gene therapy

Cell-based gene therapy typically means that the process of altering the genetic mutations that cause disease happens outside of the body on blood cells harvested from the patient. Stem cells are self-renewing and have the potential to develop into many other cells in the body. Blood-forming stem cells are one target for stem cell–based gene therapies. Immune cells such as T-lymphocytes are another target (see Pediatric Cancer Immunotherapy Program).

Blood-forming stem cells make the other cells in the blood, including red blood cells, platelets, and immune cells, otherwise called white blood cells. Blood-forming stem cells can be modified with gene therapy to transform diseases caused by a variety of genetic mutations. Blood-forming stem cells are collected from you or your child’s blood using a process called mobilized apheresis. This process is like donating platelets, but it takes four to six hours.

Next, the blood forming stem cells are modified. This can be done in different ways. One way uses a viral vector to add a working copy of the mutated gene to your or your child’s stem cells. The vector is made from a virus, but the part that can make people sick has been removed, and its only job is to help the new gene get into your or your child’s stem cells. Another way is to use CRISPR technology to edit genes, causing them to turn off or on, thereby changing the proteins that the genes make and the disease that these proteins cause. CRISPR can also be used to correct a genetic mutation—acting like scissors to cut the place of the mutation and then paste in the correct copy of the gene.

Before the modified stem cells can go back into you or your child’s body, you or your child will receive medicine to make room for the new cells in the bone marrow. This is typically a short course of chemotherapy just before the modified stem cells are infused back into you or your child, where they start producing new blood cells. The gene-modified stem cells will be infused just like any other infusion into a vein. We will continue to follow you or your child for several years after treatment.