What’s gene therapy, and what does it treat?

Packed with the genes that carry DNA and RNA, our cells hold all the information needed for our bodies to perform the many functions of life.

These genes act like instruction booklets for making different proteins that, in turn, tell our cells what they’re supposed to do.

But, sometimes, a gene is missing or not working.

When this happens, the body can’t do the job that gene was responsible for overseeing. In severe cases, this can lead to debilitating, or even fatal, disease.

A revolutionary treatment called gene therapy has opened up new possibilities for treating conditions that were previously devastating, but what exactly is gene therapy, and how does it trigger such drastic changes?

Types of gene therapy

Adding genes

One approach to gene therapy involves injecting a missing or malfunctioning gene into a patient’s bloodstream.

The needed gene is created in a lab specifically for the disease being treated and loaded onto a carrier — called a vector — to transport it into the body. This carrier is often a deactivated virus.

The carrier is targeted to a specific organ and often replicates the gene for the rest of the patient’s life. This boosts the body’s ability to do the job of the previously missing or broken gene.

The U.S. Food and Drug Administration has approved this type of gene therapy to treat spinal muscular atrophy and Duchenne muscular dystrophy – childhood diseases that affect control and development of the muscles – and AADC deficiency, a rare developmental disability.

This type of therapy has also been approved for certain types of the bleeding disorder hemophilia.

While virus-based therapy is sometimes injected into the bloodstream, there are other means of delivery. For example, the treatment for AADC deficiency is delivered directly into the brain.

A therapy for Leber’s congenital amaurosis, a childhood eye disease that often leads to blindness, is injected beneath the retina of the eye as a one-time treatment.

A product that treats a blistering skin condition called dystrophic epidermolysis bullosa is applied to the skin after being mixed into a gel, while an eyedrop formulation recently restored vision in a teenage patient with the disease. A gene therapy for bladder cancer is injected into the bladder. Neither of these therapies permanently modifies DNA, so they’re not one-time treatments.

Continuing clinical trials seek to apply gene therapies that supply missing genes to several diseases and conditions.

At Ohio State, neurology researchers are developing treatments that supply gene therapies directly to the brain to treat Parkinson’s disease and Alzheimer’s disease.

They’re also working to apply the science to a number of other brain-related conditions, including alcohol use disorder.

Ohio State retina specialists are exploring new ways to deliver genes to the eyes to address night blindness, color blindness, light sensitivity and vision loss.

Repairing genes

Gene-editing technology called CRISPR genome editing has been developed to remove, add or replace genes.

In December 2023, the FDA approved the first CRISPR-based therapy, which treats sickle cell disease, an inherited blood disorder that affects the protein in red blood cells that carries oxygen throughout the body. One of the first adult patients in the world to receive this therapy got his treatment at The Ohio State University Comprehensive Cancer Center – James Cancer Hospital and Solove Research Institute, having traveled from the United Arab Emirates. After a life of debilitating pain, he was effectively cured.

Several other CRISPR-based therapies are in development.

Treatments for diseases that cause ongoing damage to the brain and nervous system are being advanced by Ohio State’s Krystof Bankiewicz, MD, PhD, alongside researchers at the University of California San Francisco and at the University of California Berkley’s Innovative Genomics Institute. Among the collaborators is Jennifer Doudna, PhD, who co-developed CRISPR genome editing and was co-recipient of the 2020 Nobel Prize in Chemistry.

They aim to develop CRISPR-based treatments for amyotrophic lateral sclerosis (ALS), commonly known as Lou Gehrig’s disease, and Huntington’s disease, a rare, fatal condition in which nerve cells in the brain break down.

Deactivating genes

Sometimes a gene is creating a toxic protein, so it’s deactivated or “silenced,” which reduces the likelihood that someone will develop a certain disease.

This is done with RNA therapy, using a short strand of RNA that prevents the protein from being made. These treatments have to be repeated regularly.

Combining gene- and cell-based therapies

In some cases, gene therapy is performed on a patient’s cells after those cells have been removed from the body. Then, the modified cells are returned through infusion or transplantation. This also can be done with donor cells.

This type of therapy is now being applied to sickle cell disease and other blood disorders and to certain diseases that affect the brain. Further, a recently approved therapy treats a rare skin condition by modifying a patient’s cells and grafting them in sheets onto wounds.

Gene therapy vs. genetic medicine

Gene therapy is different from using genetics to understand and treat illness. Genetic medicine involves experts locating and examining a patient’s DNA to determine if they lack specific genes and using what they find to diagnose disease and target therapies.

For example, children with cystic fibrosis are diagnosed based on lack of a specific set of genes that leads to mucus forming in the lungs. Their treatments – physical therapy and medication – are based on those genetic findings. However, while gene therapies are being explored to treat cystic fibrosis, there are no such therapies available to date.

Genetic medicine is used to diagnose disease and target treatments across medical specialties.

Delivering hope with gene therapy

Gene therapy is already giving hope to families whose children are born with devastating conditions, and experts at Ohio State are striving to expand access to additional lifechanging therapies to a broader range of patients.

As physician-scientists continue to collaborate on today’s most challenging medical questions, additional cures are on the horizon.

Learn more about the work happening at Ohio State by visiting the Gene Therapy Institute website.

Editor’s Note: This article has been reviewed for accuracy by experts at The Ohio State University Gene Therapy Institute.