How Does Gene Therapy Work?

Types of Gene Therapy

There are basically 2 types of gene therapy, and several approaches within those types. Here you’ll learn about how different gene therapy approaches are used to treat diseases.

How does gene therapy work?
Gene therapy is an investigational therapeutic approach that aims to add, delete, or correct genetic material in order to treat a disease. The addition, deletion, or correction of genetic material changes how a protein, or group of proteins, is produced by the cell. This change gives the cell a new set of instructions that can help treat the disease at the genetic level.

Gene therapy is an investigational therapeutic approach that aims to add, delete, or correct genetic material in order to treat a disease. The addition, deletion, or correction of genetic material changes how a protein, or group of proteins, is produced by the cell. This change gives the cell a new set of instructions that can help treat the disease at the genetic level.

What are the types of gene therapy?
Overall, there are two types of gene therapy being studied: gene addition and gene editing. Gene addition does what it says—adds genetic material to a person’s cells. Within gene editing, there are a few different techniques to achieve a therapeutic effect: gene insertion, gene inactivation (also called silencing, knockdown, or knockout), and gene correction. Think of it like editing a term paper: you add what’s missing; take out what’s not working; and if it doesn’t flow, you take it apart and put it back together again (or edit).
gene therapy gene addition gene editing

Overall, there are two types of gene therapy being studied: Gene additionadds functioning genetic material to do the work of a faulty gene

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 and Gene editingan umbrella term used to describe gene therapy approaches to modifying a faulty gene; these include both disruption/inactivation and correction/insertion

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. Gene addition does what it says—adds genetic material to a person’s cells. Within gene editing, there are a few different techniques to achieve a therapeutic effect: Gene insertionapplies genetic material in order to treat a disease at the genetic level

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, Gene inactivationan approach in gene therapy that turns off or reduces the function of a gene in order to have a therapeutic effect

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 (also called silencing, knockdown, or knockout), and Gene correctioncorrects a faulty gene with functional genetic material with the aim of correcting the faulty gene

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. Think of it like editing a term paper: you add what’s missing; take out what’s not working; and if it doesn’t flow, you take it apart and put it back together again (or edit).

Which technique is appropriate?
The disease and gene being targeted play a major role in informing which of the above gene therapy techniques can be used. Depending on the specific genetic mutation and how it manifests in the body, scientists and clinical researchers decide where to begin their work. Researchers may try more than 1 gene therapy technique in order to achieve the same goal. If a disease is caused by a single specific genetic mutation, it allows researchers to target that mutation to bring about therapeutic effect. Similarly, if the body is not producing enough of a certain protein, genetic material that can help to increase production of that protein may be inserted.

The disease and gene being targeted play a major role in informing which of the above gene therapy techniques can be used. Depending on the specific genetic Mutationa change in a DNA sequence

See glossary for more terms >
and how it manifests in the body, scientists and clinical researchers decide where to begin their work. Researchers may try more than 1 gene therapy technique in order to achieve the same goal. If a disease is caused by a single specific genetic mutation, it allows researchers to target that mutation to bring about therapeutic effect. Similarly, if the body is not producing enough of a certain Proteinclass of molecules composed of one or more chains of amino acids that perform different functions the body needs including structure, function, and regulation of tissues and organs

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, genetic material that can help to increase production of that protein may be inserted.1

Differences in Gene Therapy Techniques
   Gene Addition  Gene Editing

 Disruption or Inactivation Correction or Insertion
Overall technique Adds functioning genetic material to
do the work of a faulty gene2,3
Creates targeted breaks in DNA without instructions to repair those breaks, with the aim of disrupting or inactivating the function of a gene4 Creates targeted breaks in DNA with instructions to repair those breaks, with the aim of correcting the function of a gene or inserting functioning genetic material5
Common research targets Genetic disease and immuno-oncology6 Oncology, genetic disease, infectious disease, and neurodegenerative disease6-8 Genetic disease and immuno-oncology6,9,10

Overall technique  Common research targets
 Gene Addition
Adds functioning genetic material to do the work of a faulty gene2,3  Genetic disease and immuno-oncology6
 Gene Editing
 Disruption or Inactivation
Creates targeted breaks in DNA without instructions to repair those breaks, with the aim of disrupting or inactivating the function of a gene4 Oncology, genetic disease, infectious disease, and neurodegenerative disease6-8
Correction or Insertion
Creates targeted breaks in DNA with instructions to repair those breaks, with the aim of correcting the function of a gene or inserting functioning genetic material4 Genetic disease and immunooncology6,9,10
Gene-ius Questions

CAR T-cell therapya treatment where a person's T cells are changed in a lab and then infused back into the person’s body to help attack cancer cells

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, categorized as a gene-based cellular immunotherapy, involves harvesting the person’s own T-cellsa type of white blood cell that is in charge of the body's immune response to pathogens

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, genetically engineering those cells to express a specific synthetic receptor (creating CAR T cells).11 One currently approved CAR T-cell therapy uses a lentiviral vector to add genetic material to T-cells in order to target and attack cancer cells.11,12 This new genetic material instructs T-cells to express an artificial receptor, called a chimeric antigen receptor (CAR), that enables the T cells to recognize and attack cancer cells, thus becoming CAR T-cell therapy.13, 14

Image of CAR T-cell therapy
Gene Therapy Techniques
Discover the different types of gene therapy and how they work
Gene Therapy Techniques
Discover the different types of gene therapy and how they work

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References

1. STAT Reports. The STAT guide to viral vectors, the linchpin of gene therapy. STAT News; 2019. 2. FDA Commissioner. What is gene therapy? How does it work? US Food and Drug Administration. Accessed March 1, 2020. https://www.fda.gov/consumers/consumer-updates/what-gene-therapy-how-does-it-work 3. Collins M, Thrasher A. Gene therapy: progress and predictions. Proc Biol Sci. 2015;282(1821):20143003. 4. Guha TK, Wai A, Hausner G. Programmable genome editing tools and their regulation for efficient genome engineering. Comput Struct Biotechnol J. 2017;15:146-160.3 5. Yanik M, Müller B, Song F, et al. In vivo genome editing as a potential treatment strategy for inherited retinal dystrophies. Prog Retin Eye Res. 2017;56:1‐18. 6. National Heart, Lung, and Blood Institute. Gene therapies, overview. Accessed March 21, 2020. https://www.nhlbi.nih.gov/health-topics/genetic-therapies 7. Grant SG, Campbell CE, Duff C, et al. Gene inactivation as a mechanism for the expression of recessive phenotypes. Am J Hum Genet. 1989;45:619-634. 8. Koshravi MA, Abbasalipour M, Concordet J-P, et al. Targeted deletion of BCL11A gene by CRISPR-Cas9 system for fetal hemoglobin reactivation: a promising approach for gene therapy of beta thalassemia disease. Eur J Pharmacol. 2019;854:398-405. 9. Keeler AM, ElMallah MK, Flotte TR. Gene therapy 2017: progress and future directions. Clin Transl Sci. 2017:10(4):242-248. 10. Chandler RJ, Venditti CP. Gene therapy for metabolic diseases. Transl Sci Rare Dis. 016;1(1):73-89. 11. NIH National Cancer Institute. NCI dictionary of cancer terms. CAR T-cell therapy. Accessed March 1, 2020. https://www.cancer.gov/publications/dictionaries/cancer-terms?expand=C 12. Almasbak H, Aarvak T, Vemuri MC. CAR T cell therapy: a game changer in cancer treatment. J Immunol Res. 2016;2016:5474602. 13. American Society of Gene & Cell Therapy (ASCGT). Learn about blood cancers and CAR T-cell therapy. Accessed March 1, 2020. https://www.asgct.org/research/news/december-2019/blood-cancers-car-t-cell-therapy 14. Ellebrecht CT, Bhoj VG, Nace A, et al. Reengineering chimeric antigen receptor T cells for targeted therapy of autoimmune disease. Science. 2016;353(6295):179-184.

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