Gene therapy is the introduction, removal or change of genetic material, specifically DNA (deoxyribonucleic acid) or RNA (ribonucleic acid), in the cells of a person. Gene therapy is designed to treat genetic disease.1

  • Genes are found in the body’s cells and are made of up of DNA. Some genes tell the body how to make molecules called proteins.2
  • Proteins do many important jobs in cells. Some proteins give cells structure. Other proteins protect cells from viruses and bacteria. Some proteins move waste out of cells.3

Sometimes, a person is born with a gene that does not work properly. This is called a mutation. The mutation doesn’t allow the gene to give the right directions to the body. In some cases, gene mutations can cause disease.4 The goal of gene therapy is to replace a non-working gene with a working copy.5

How Does Gene Therapy Work?

There are different types of gene therapy. The gene therapy used will depend on the type of disease being treated.

Transferring (Replacing)

Gene transfer uses a vector, or carrier, to bring a new gene into the cell. The new gene replaces the non-working (mutated) gene or genes that cause the disease.

Silencing

Gene inactivation or gene silencing is designed to stop a mutated gene from causing disease.5

Introducing

Scientists can add new genes to cells using gene therapy. These genes can attack tumor cells or stop tumors from growing.6

Editing

Gene editing is when scientists add, remove, or change the DNA of a specific cell or cells in the body to correct an existing gene mutation.7

Patients can receive gene therapy in different ways. Gene therapies are usually given in a hospital by infusion or injection.8

More on Gene Transfer and Vectors

It is difficult to insert a new gene into a cell in the body. First, scientists must figure out which gene or genes are causing a disease. Next, they must create a working copy of the gene or genes in a laboratory. Once they create a working copy of the gene, it has to be placed into a vector. A vector is a carrier that allows the new gene to enter the cell. Once the gene is successfully inside of the cell, it can potentially help make working proteins that the body needs. In this way, gene therapy corrects the cause of the disease, rather than only treating symptoms.9

Vectors are often made from viruses because viruses can easily enter cells. The viruses that are used for gene therapy are changed so that they cannot cause disease. The type of vector used depends on the disease.

  • The vector types that are used today are different from the ones used in previous gene therapy trials.
  • Today’s vectors are much safer than ones used in the past.
  • The adeno-associated virus (AAV) is a common type of vector.
  • Many versions of the AAV vector have been studied in animals and humans.7

Potential Side Effects of Gene Therapy

Some studies have shown that there are health risks associated with gene therapy.10 Because gene therapy is so new, scientists and researchers don’t yet know all of the potential side effects. If you are considering gene therapy, it’s important to discuss the potential benefits and risks with your doctor.

Review of Important Words
Genes Genes provide the instructions for cells to make proteins. Genes carry information that determines your traits, such as height and hair color.
DNA Deoxyribonucleic acid, or DNA, is the material that makes up genes. DNA is inherited from a person’s mother and father.
Gene mutation A permanent change in DNA that differs from what is found in most people. Gene mutations can cause genes to stop working or to work incorrectly.11
Cells Cells are the basic building blocks of all living things.12
Proteins Proteins are molecules in the body that do most of the work in cells.3
Vector A vector is a virus that has been changed so that it does not multiply or cause infection. It is used to help genes enter into cells during gene therapy.
Adeno-associated virus (AAV) A type of virus that is used in gene therapy to carry genetic information into a cell. It is changed so that it cannot make copies of itself.

Additional Resources on Gene Therapy

Genetics Home Reference

What is gene therapy?

American Society of Gene & Cell Therapy

Gene Therapy 101

Gene Therapy Clinical Trials

Ultragenyx is currently working to develop gene therapies for glycogen storage disease type 1a (GSD1a) and ornithine transcarbamylase (OTC) deficiency.

DTX401 is an investigational gene therapy designed to address a non-working gene that causes an enzyme deficiency in people with GSD1a, which results in the inability to regulate blood sugar (glucose).13

Ultragenyx is currently enrolling a Phase 1/2, open-label safety and dose-finding study of DTX401 in adults with GSD1a.

To be eligible to participate in this study, you should be 18 years of age or older with a diagnosis of GSD1a that has been confirmed by molecular testing and a documented history of one or more hypoglycemic events.14 This is not all of the eligibility criteria. Learn more about the DTX401 study at clinicaltrials.gov.

You can also participate in an Online Survey about your experience with GSD1a.

DTX301 is an investigational gene therapy designed to address a genetic mutation in a liver enzyme which causes ammonia to build up in the bloodstream of people with OTC deficiency.15

Ultragenyx is currently enrolling a Phase 1/2 open-label, single arm, multicenter, safety and dose finding study in adults with late-onset OTC deficiency.

To be eligible to participate in this study, you should be 18 years of age or older with a diagnosis of late onset OTC deficiency that has been confirmed by enzymatic, biochemical or molecular testing and a documented history of one or more hyperammonemia events.16 This is not all of the eligibility criteria. Learn more about the DTX301 study at clinicaltrials.gov.

You can also participate in an Online Survey about your experience with OTC deficiency.

References

1. Gene Therapy Basics. American Society of Gene & Cell Therapy. https://www.asgct.org/education/gene-therapy-basics. Accessed April 18, 2019. 2. What is a gene? National Institutes of Health. Genetics Home Reference. https://ghr.nlm.nih.gov/primer/basics/gene. Published March 19, 2019. Accessed March 28, 2019. 3. What are proteins and what do they do? National Institutes of Health. Genetics Home Reference. https://ghr.nlm.nih.gov/primer/howgeneswork/protein. Published March 19, 2019. Accessed Marc 28, 2019. 4. What is a gene mutation and how do mutations occur? National Institutes of Health. Genetics Home Reference. https://ghr.nlm.nih.gov/primer/mutationsanddisorders/genemutation. Published March 19, 2019. Accessed Marc 28, 2019. 5. University of Utah. Approaches to Gene Therapy. Learn. Genetics. Genetic Science Learning Center. https://learn.genetics.utah.edu/content/genetherapy/approaches/. Accessed Marc 28, 2019. 6. Gene and Cell Therapy FAQ’s. American Society of Gene & Cell Therapy. https://www.asgct.org/education/more-resources/gene-and-cell-therapy-faqs. Accessed April 18, 2019. 7. What are genome editing and CRISPR-Cas9? National Institutes of Health. Genetics Home Reference. https://ghr.nlm.nih.gov/primer/genomicresearch/genomeediting. Accessed April 15, 2019. 8. How does gene therapy work? National Institutes of Health. Genetics Home Reference. https://ghr.nlm.nih.gov/primer/therapy/procedures. Published March 19, 2019. Accessed Marc 28, 2019. 9. American Society of Gene & Cell Therapy. Gene Therapy 101.
https://www.asgct.org/education/different-approaches. Accessed March 28, 2019. 10. Is gene therapy safe? National Institutes of Health. Genetics Home Reference. https://ghr.nlm.nih.gov/primer/therapy/safety. Accessed April 15, 2019. 11. Vachani, Carolyn. What is Gene Therapy?. Abramson Cancer Center of the University of Pennsylvania. https://www.oncolink.org/cancer-treatment/immunotherapy/what-is-gene-therapy. Updated June 7, 2018. Accessed Marc 28, 2019. 12. What is a cell? Genetics Home Reference. https://ghr.nlm.nih.gov/primer/basics/cell. Accessed April 18, 2019. 13. DTX 401 for GSDIa. Ultragenyx Pharmaceutical. https://www.ultragenyx.com/pipeline/dtx-401-for-gsd1a/. Accessed March 28, 2019. 14. Safety and Dose-Finding Study of DTX401 (AAV8G6PC) in Adults With Glycogen Storage Disease Type Ia (GSDIa). ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT03517085?term=dtx401&cond=gsd1a&rank=1Clinicaltrials.gov. Accessed April 15, 2019. 15. DTX 301 for OTC. Ultragenyx Pharmaceutical. https://www.ultragenyx.com/pipeline/dtx-301-for-otc/. Accessed March 28, 2019. 16. Safety and Dose-Finding Study of DTX301 (scAAV8OTC) in Adults With Late-Onset OTC Deficiency (CAPtivate). ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT02991144?term=dtx+301&rank=1. Accessed April 15, 2019.