Science Simplified: What is Gene Therapy?

Want to learn about scientific topics without needing a PhD? Check out the Science Simplified blog from TESS Research Foundation! Dr. Tanya Brown, PhD, works with researchers to make science accessible and empower rare disease community members with scientific knowledge. Dr. Brown has over a decade of experience in neurodevelopmental research and is currently the Scientific Director for TESS Research Foundation. Please reach out to her at [email protected] if you have questions or comments.

Thank you to Catherine Nicholas, a graduate student at the University of Colorado Anschutz Medical Campus, for writing this article about gene therapy. This article was edited by Tanya Brown, PhD, Research Program Manager, and Emily Hsu, Operations Manager, at TESS Research Foundation.

What is Gene Therapy and how does it work?

This may or may not come as a surprise, but many current medicines and treatments don’t directly target the actual cause of illness. Instead, they work to alleviate the symptoms of the disease. However, there is now an emerging treatment option called gene therapy, which is all about directly targeting the cause of the disease, by adding, removing, or editing a gene inside your cells.

How does this work? Our bodies are made up of many cells that contain genes (the body’s recipes for making the proteins and factors you need to stay healthy). These gene recipes are important to make our bodies work properly. Sometimes these recipes have an error, like a missing or wrong instruction, which tells the body to use the wrong ingredient and that changes the final product. These errors can lead to issues in how the body works, similar to replacing salt for sugar when making a batch of cookies. The end result may look like a cookie, but it doesn’t taste like it’s supposed to.

These changes in the recipe, or gene mutations, occur frequently in rare diseases. To directly target the gene mutations that cause rare diseases, gene therapy is adding, removing, or editing the gene inside your cells, in order to give your body the right recipe.

Gene Therapy Overview 

Gene therapy is a new field of research that has the potential to help many different rare diseases that are caused by a change (a mutation) in a single gene. If you search the term “gene therapy” where scientific papers are stored, such as the search engine PubMed, you will see an explosion in new research in the last 30 years, with 1,051 papers published in 1990, and 29,002 papers published in 2020.  Scientists are working hard to develop gene therapies for different diseases, including SLC13A5 deficiency. This article will help explain why gene therapies may be a good option for diseases like SLC13A5 deficiency and what is currently being done to provide treatment for these patients.

Gene therapy can cover several different techniques and methods of treatment.  You may have heard about CRISPR gene editing, which won the Nobel Prize in Chemistry in 2020 and has gotten a lot of press recently.  This method takes an engineered bacterial enzyme called ‘Cas9’ and a piece of new genetic material to deliver to your cells.  Cas9 actually finds the site in your gene that needs some help, opens it up, and replaces the old sequence with the new, corrected one.

In another therapy, rather than adding an enzyme that modifies genes inside of a cell, cells are modified outside the body and added back to the patient. This involves taking blood from a patient, isolating individual cells, and changing them in the lab so that they recognize and attack other invasive cancer cells before they are put back into the body (CAR-T therapy).

Another gene therapy method delivers the correct version of a mutated gene to the cells via a delivery system. This delivery system can use the outer shell of a virus—also called a vector—to deliver the correct gene to cells.  In other words, a non-harmful virus is modified to deliver the correct recipe the body needs to cells.  The virus is able to get inside human cells and deliver the new genetic material so that the cells in the body can work properly.

What’s different about these treatments as compared to taking antibiotics or going through chemotherapy, is that these methods are typically a single dose and a single treatment meant to permanently fix the genetic issue.  Scientific investigations are ongoing and are showing great promise. Gene therapy is also unique in the way that it specifically targets the biological problem rather than just treating the symptoms. The viral vector delivery method is currently under development from Taysha Gene Therapies for the treatment of SLC13A5 deficiency.

Adeno-Associated Virus (AAV) Gene Therapy 

The type of gene therapy currently under development for SLC13A5 deficiency uses an adeno-associated virus (AAV) to deliver the correct genetic sequence to cells with a broken copy of the SLC13A5 gene. This virus does not cause illness or disease, which is why it has been chosen as the way to introduce the therapy to people who need it.

AAVs come in a number of similar types, and the specific one under development for SLC13A5 deficiency is AAV9. This particular virus has a greater ability to target brain cells, which is especially important for treating SLC13A5 deficiency. Once the virus finds a cell, it is able to enter and release the cargo containing the correct gene. This cargo is the recipe that will be followed to make a working version of the protein. The cargo will not be passed down to the children of someone who has been given this treatment.

Let’s walk through how AAV gene therapy can treat rare genetic diseases using SLC13A5 deficiency as an example. In SLC13A5 deficiency, patients have a broken copy of the SLC13A5 gene, which prevents a protein (NaCT) from moving citrate from outside the cell to inside the cell. Using gene therapy, a correct version of the SLC13A5 gene will be delivered to cells. This gene will provide the recipe for a working version of the NaCT protein and cells will be able to move citrate into a cell. Before this treatment, the SLC13A5 mutation didn’t allow the transporter to work properly and cells couldn’t move citrate into the cells. In fact, the therapy under development has shown that after treatment in mice, citrate moves successfully into cells, and seizure activity significantly decreases.


Gene therapy is an exciting therapeutic option that may become available for patients with rare diseases. There have been many years of research leading this new strategy to make patients’ lives better. The treatment timeline from discovering something in the lab to testing its efficacy and safety in humans through clinical trials to a doctor giving a patient a prescription takes a long time: the whole process can take more than 10 years.

An important consideration is that this is a one-attempt therapy. If it doesn’t work, it is not able to be re-dosed or given in a greater dose later on, at least in the same way that it was initially delivered. This is because your body may recognize the AAV delivery package the second time. This means your immune system may believe a second dose of gene therapy to be a threat and prevent delivery to your cells.

In conclusion, gene therapy is a promising therapy, especially for rare diseases caused by changes to a single gene. There is a lot to learn and as scientists continue to investigate gene therapy, our knowledge will continue to grow. If you want to learn more, we have posted some resources below. You can also ask us more about gene therapy by contacting Tanya Brown at [email protected].

Other sources to check out for more information:

COVID Vaccines and Gene Therapy 

NORD YouTube 

Mayo Clinic 


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