What is Gene Therapy?
Basics of Gene Therapy
What is gene therapy?
Gene therapy is a type of treatment that uses genetic material with the goal of changing the course of a disease. It is a therapeutic approach that is being investigated for the treatment of multiple diseases. Though many gene therapies are currently in early research or clinical trials 2 gene therapies have already been approved by the US Food and Drug Administration (FDA) as of June 2021.
See glossary for more terms > is a type of treatment that uses genetic material with the goal of changing the course of a disease. It is a therapeutic approach that is being investigated for the treatment of multiple diseases.1 Though many gene therapies are currently in early research or clinical trials, 2 gene therapies have already been approved by the US Food and Drug Administration (FDA) as of June 2021.2-4
What is the goal of gene therapy?
The goal of gene therapy is to treat diseases at the genetic level (the source). Gene therapy is a promising treatment option that is being studied for a number of diseases including inherited diseases and cancers.
The goal of gene therapy is to treat diseases at the genetic level (the source). Gene therapy is a treatment method that is being studied for a number of diseases, including inherited diseases and cancers.1
For over 100 years, scientists have studied the human body and the building blocks of DNA. With each mark of progress comes a better understanding of how our bodies work at the genetic level and how we may be able to keep them healthy and free from disease.5
Today, gene therapy continues to build on that strong foundation of DNA research.1
There are 2 major types of gene therapy:
GENE ADDITION
The addition of genetic materials into the cell to enable the body to produce a functional protein that it could not adequately make before.6,7,8
GENE EDITING
The process of directly changing, or editing, a specific site in the genome. The techniques in this therapy include gene correctionGene correctiona technique that corrects a faulty gene with functional genetic material with the aim of correcting the faulty gene
See glossary for more terms >/insertionGene insertiona technique that applies genetic material in order to treat a disease at the genetic level
See glossary for more terms > and gene inactivation/disruptionGene inactivationan approach in gene therapy that turns off or reduces the function of a gene in order to have a therapeutic effect
See glossary for more terms >.6,9
Overview of gene addition and gene editing
| Gene addition | Gene editing |
||
| Mechanism (how it works) | Inserts functional copies of a gene into target cells using a vectorVectora delivery system used to introduce genetic material into the nucleus See glossary for more terms > to overcome the cells' use of a faulty gene6,7 |
Gene inactivation or disruption | Gene correction or insertion |
| Creates targeted breaks in DNA without instructions to repair those breaks, with the aim of disrupting or inactivating the function of a gene10 | Creates targeted breaks in DNA with instructions to repair those breaks, with the aim of correcting the function of a gene by inserting functioning genetic material9 | ||
| Key components | Viral vectors containing functional genetic material6,7 | A targeted editing nucleaseNucleasean enzyme that is capable of cleaving the bond between two bases in a nucleic acid at a specific sequence See glossary for more terms >, with or without genetic material to repair DNA breaks9 |
|
| Manufacturing | Therapeutic gene is engineered and packaged into vector for delivery to cells6,7 | Nuclease and genetic material is engineered and delivered to cells9 | |
| Gene Addition | |
| Mechanism (how it works) | |
| Inserts functional copies of a gene into target cells using a vectorVectora delivery system used to introduce genetic material into the nucleus See glossary for more terms > to overcome the cells' use of a faulty gene6,7 |
|
| Key Components | |
| Viral vectors containing functional genetic material6,7 | |
| Manufacturing | |
| Therapeutic gene is engineered and packaged into vector for delivery to cells6,7 | |
| Gene Editing | |
| Mechanism (how it works) | |
| Gene inactivation or disruption | Gene correction or insertion |
| Creates targeted breaks in DNA without instructions to repair those breaks, with the aim of disrupting or inactivating the function of a gene10 | Creates targeted breaks in DNA with instructions to repair those breaks, with the aim of correcting the function of a gene by inserting functioning genetic material9 |
| Key Components | |
| A targeted editing nucleaseNucleasean enzyme that is capable of cleaving the bond between two bases in a nucleic acid at a specific sequence See glossary for more terms >, with or without genetic material to repair DNA breaks9 |
|
| Manufacturing | |
| Nuclease and genetic material is engineered and delivered to cells9 | |
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What are the potential risks of gene therapy?
As with any treatment, there are risks associated with gene therapy. Risk depends on the type of gene therapy, type of vector (used to deliver the gene therapy), and the administration method. Some risks can be serious.11 The safety of gene therapy will continue to be assessed over time.
Potential risks of gene therapy include:
| Risk | Response |
| Immune reaction | In gene therapy, an immune reaction is an unintentional response from your body. An immune reaction to the gene therapy delivery system or the therapeutic protein could make the therapy less efficient. Antibodies against the gene therapy delivery system can prevent a second dose being administered, if one is needed. Risk of an immune response can be controlled by tailoring the viral dose to the patient.11 |
| Insertional mutagenesis | The consequences of the insertion of DNA in unwanted locations can result in uncontrolled cell division. Insertional mutagenesis is typically associated with gene therapies that integrate into the genome (an example of this is insertional oncogenesis—healthy cells mutating into cancerous ones). There continues to be a risk of insertional mutagenesis, but every case to date was connected to older technologies that were not yet refined for additional safety. The latest technologies could minimize these risks by not readily integrating into the genome or by using self-inactivating technologies that cannot activate themselves.11 |
| Off-targeting | In the process of gene editing, there is a possibility that the technique used could make changes at a different site than the intended. This can cause changes to healthy genes, which may have unintended effects.11 |
| Unintentional gene inactivation | With any type of gene therapy, there is the risk of unexpected complications that unintentionally prevent the function of another important gene.11 |
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Throughout the gene therapy treatment process, the treating physician and supportive care team provide careful monitoring and management. During the recovery process after gene therapy, they help to manage safety concerns.
As with any treatment, patients and caregivers should always discuss their treatment plan and the risks and benefits of a specific gene therapy with their physician.
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Gene-ius Questions
To help understand gene therapy, here is a general example of a gene therapy and how it moves from research to a potential reality:
- Scientists discover the genetic basis of a disease, which might be a mutation in a single gene.12
- Scientists target their research on ways to modify the specific mutation.13
- Different gene therapy techniques are explored in a laboratory in order to figure out which are most effective and show the most promise in treating a genetic disease.13
- Once scientists find a technique that they believe has the potential to work, the gene therapy goes through preclinical research and rigorous clinical trials to evaluate the safety and efficacyEfficacythe ability of a medication to achieve its desired effect
See glossary for more terms > of the treatment.14 - Successful completion of clinical trials may result in approval by regulatory authorities such as European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) and a specific gene therapy becoming available for people with the disease.14,15
To learn more about the development and history of gene therapy, click here.
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References
1. National Institutes of Health. Genetics Home Reference. Help me understand genetics. Accessed July 1, 2021. https://medlineplus.gov/download/genetics/understanding/primer.pdf 2. Food and Drug Administration. Approved Cellular and Gene Therapy Products. Accessed July 28, 2021. https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/approved-cellular-and-gene-therapy-products 3. Zolgensma (onasemnogene abeparvovec-xio) [prescribing information]. Bannockburn, IL: Kite Novartis, Inc.; 2019. 4. Luxturna (voretigene neparvovec-rzyl) [prescribing information]. Philadelphia, PA: Kite Spark Therapeutics, Inc.; 2021. 5. Wirth T, Parker N, Ylä-Hertuala. History of gene therapy. Gene. 2013;525(2):162-169. 6. FDA Commissioner. What is gene therapy? How does it work? US Food and Drug Administration. Accessed July 1, 2021. https://www.fda.gov/consumers/consumer-updates/what-gene-therapy-how-does-it-work 7. Collins M, Thrasher A. Gene therapy: progress and predictions. Proc Biol Sci. 2015;282(1821):20143003. 8. STAT Reports. The STAT guide to viral vectors, the linchpin of gene therapy. STAT News; 2019. 9. Encyclopedia Britannica. Gene editing. Accessed July 1, 2021. https://www.britannica.com/science/gene-editing 10. Zhang X, Piedrahita JA. Advances in the generation of transgenic domestic species via somatic cell nuclear transfer. In: Cibelli J, Gurdon J, Wilmut I, et al, Eds. Principles of Cloning. 2nd Edition. Elsevier;2014:95-106. 11. Goswami R, Subramanian G, Silayeva L, et al. Gene therapy leaves a vicious cycle. Front Oncol. 2019;9:297 12. Amberger JS, Bocchini CA, Scott AF, Hamosh A. OMIM.org: leveraging knowledge across phenotype-gene relationships. Nucleic Acids Res. 2019;47(D1):D1038-D1043. 13. Food and Drug Administration. Human gene therapy for rare diseases: guidance for industry. January 2020. Accessed July 1, 2021. https://www.fda.gov/media/113807/download 14. Food and Drug Administration. Development & approval process: drugs. Accessed July 1, 2021. https://www.fda.gov/drugs/development-approval-process-drugs 15. European Medicines Agency. From laboratory to patient: the journey of a medicine assessed by EMA. Accessed July 1, 2021. https://www.ema.europa.eu/en/documents/other/laboratory-patient-journey-centrally-authorised-medicine_en.pdf