How Does Gene Therapy Work?

Types of Gene Therapy

There are basically 2 types of gene therapy, and several techniques within those types. Here you’ll learn about how different gene therapy types and techniques are used to treat diseases.
How Does
Gene Therapy Work
Gene addition
and gene editing
Additional Therapies:
CAR T-cell therapy
How Does
Gene Therapy Work
Gene addition
and gene editing
Additional Therapies:
CAR T-cell therapy

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. Modifying genetic material changes how a protein, or group of proteins, is produced by the cell. In other words, gene therapy aims to give the cell a new set of instructions in order to change either the amount or type of protein that is produced. By changing the instructions for the production of protein, gene therapy treats the disease at the genetic level.

Gene therapy is a therapeutic approach that aims to add, delete, or correct genetic material in order to treat a disease. Modifying genetic material changes how a protein, or group of proteins, is produced by the cell. In other words, gene therapy aims to give the cell a new set of instructions in order to change either the amount or type of protein that is produced. By changing the instructions for the production of protein, gene therapy treats the disease at the genetic level.1,2

Looking to learn more about the treatment process? CLICK HERE.

Gene addition and gene editing

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

See glossary for more terms > and Gene editingthe creation of targeted double-stranded breaks in DNA, with or without repair instructions, to disrupt or correct the function of a gene

See glossary for more terms >.

Gene addition treats diseases at the genetic level by adding genetic material to a person’s cells to compensate for a missing or faulty gene.1

Gene editing treats diseases at the genetic level by directly modifying a patient’s DNA through a number of different techniques. These techniques are Gene 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 > (also called gene silencing, knockdown, or knockout), and Gene correctiona technique that corrects a faulty gene with functional genetic material with the aim of correcting the faulty gene

See glossary for more terms >/Gene insertiona technique that applies genetic material in order to treat a disease at the genetic level

See glossary for more terms >.1

Gene addition

How does gene addition work?

Gene addition is a common gene therapy technique being explored for Single-gene diseasestypes of diseases, also called monogenic diseases, in which a mutation is present in one gene only

See glossary for more terms >—disorders where a mutation occurs in one or both sets of your genes.2,3 This gene therapy technique usually involves the insertion of functional (or healthy) copies of a gene (otherwise known as a Transgenea portion of DNA from one organism inserted into the genome of another organism

See glossary for more terms >) into a person’s cells by way of a vector.4

Vectors deliver the functional gene to the patient’s cells, either in vivo or ex vivo. Once inside the cell, the transgene provides the cell with instructions that lead to the production of functional proteins. With gene addition therapy, the mutated gene does not need to be replaced or removed. This provides the cell with the instructions that lead to the production of functional genes, while not needing to replace or remove the mutated gene.5,6

Image of gene addition therapy
Explore Genehome
Want more information on vectors?
Learn About Vectors
Explore Genehome
Want more information on vectors?
Vectors

Gene addition therapies focus on treating Single-gene diseasestypes of diseases, also called monogenic diseases, in which a mutation is present in one gene only

See glossary for more terms >, which are appropriate targets because there’s only 1 mutated gene to fix. Adding a functional gene will compensate for the mutated gene. Some of these single-gene diseases include hemoglobinopathies, such as sickle cell and thalassemia, which are among the most common diseases being explored in gene therapy. Additional areas being studied for gene therapy are lung diseases, like cystic fibrosis, and blood diseases, like hemophilia.2,3,5

Explore Genehome
Gain a deeper understanding of single-gene diseases
Impact of genetic diseases
Explore Genehome
Gain a deeper understanding of single-gene diseases
Impact of genetic diseases

Gene editing

How does gene editing work?

Gene editing involves the creation of targeted breaks in the DNA, with or without instructions to repair them, through a number of different techniques.6,7

There are 2 primary techniques in gene editing: Gene 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 >, Gene correctiona technique that corrects a faulty gene with functional genetic material with the aim of correcting the faulty gene

See glossary for more terms >/Gene insertiona technique that applies genetic material in order to treat a disease at the genetic level

See glossary for more terms >.

  • “Disrupting” or “inactivating” genetic material that is responsible for the genetic disease. This can be achieved by turning off genes that cause disease or disrupting a separate gene that will compensate for the disease-causing gene8
  • “Correcting” genetic material by creating a break in the gene and providing a corrective template or “inserting” new genetic material for the cell to use to repair the mutated gene9
Image of gene editing

Gene disruption or Gene 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 > are sometimes referred to as gene silencing, knockdown, or knockout. This is when scientists turn off (or down) an existing gene to help address a genetically related health issue.8

Remember, an important function of genes is to make proteins. In some diseases, mutations in these genes may cause the gene to overproduce, or overexpress, the proteins that they make normally. The excess amounts of proteins can build up in key organs in the body and lead to the symptoms of a disease. Turning off, or inactivating, the overexpressed gene can stop its activity and treat the disease.2,5

Next Level Knowledge
There are other methods of inactivating a gene that do not require directly altering the gene itself. While this can be done in a number of ways, one involves specific molecules (called repressors or inactivators) that can bind to genes and effectively prevent the target gene from expressing itself. This can be done either through turning the gene completely off or reducing the amount it expresses itself—similar in concept to how a dimmer switch can turn down a light without turning it off. Another way involves turning on other genes that make the proteins that compensate for the mutated gene or lack of protein.2

Research is ongoing to create gene inactivation therapy that can combat cancer, blood diseases, infectious diseases, and neurodegenerative diseases. Gene inactivation also holds potential for silencing a damaging gene so that a recessive trait, or Phenotypeobservable characteristics or traits (like blood type or eye color) that come from genetic traits and/or environmental effects

See glossary for more terms >, can be expressed instead.8,10-12
Gene correction is a technique that relies on the creation of a break at a specific site in the DNA. That break is then repaired with 1 or more provided bases of DNA to correct or override the faulty gene. Gene insertion on the other hand adds a new section of DNA to the gene.9

There are many possible diseases that gene correction or gene insertion may have the potential to treat, from rare genetic diseases like cystic fibrosis to blood disorders like sickle cell disease.13-15

As research progresses and more clinical trials are conducted, we will continue to learn about what diseases may be best treated through gene editing.

What is CRISPR?

You may have heard about a specific gene editing technology called CRISPR, an acronym for the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR/Cas9)a gene editing technique that uses a specially designed RNA molecule to guide a Cas9 enzyme to a specific sequence of DNA so it can change or edit that site sequence

See glossary for more terms > system found in bacteria.20

There are 2 parts to the CRISPR system: The first is the Cas enzyme itself and the second is the guide ribonucleic acid (RNA), the tool used to locate the targeted genetic material. Cas proteins (most commonly, Cas9) are a specific class of enzymes that break the target DNA sequence. These proteins work with the guide RNA, which is engineered with a specific sequence that tells the Cas protein where to break the DNA.20,21

Once the DNA is cut, this break can be used to repair the broken gene with or without instructions on how to do so.21

Gene-ius Questions

Base editinga gene editing method to edit select bases without cleaving DNA

See glossary for more terms > is a different technique within gene editing. Remember that DNA is made from the building blocks that are paired together (A with T and C with G). The base editing process allows researchers to change these building blocks from A and T to C and G, or vice versa, but without breaking the DNA. This technique is still in early research and is continuously developing.16

How scientists determine which type of gene therapy to use

Understanding the disease, the gene being targeted, and the ultimate goal of treatment all play a major role in helping scientists decide which gene therapy types and techniques to use.

In identifying a specific genetic Mutationa change in a DNA sequence

See glossary for more terms > and how it expresses in the body, scientists and clinical researchers can decide where to begin thinking about gene therapy.5

Researchers also need to establish a treatment goal. For example, if the genetic mutation they are targeting is causing the body to not produce 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

See glossary for more terms >, they can choose a gene therapy technique that will target the mutated gene and increase protein production.5

What is CAR T-cell therapy?
CAR T-cell therapy, categorized as a gene-based cellular immunotherapy, involves harvesting the person’s own T-cells, 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. 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.

CAR T-cell therapya treatment where a person's T-cells (a part of the immune system) are genetically modified to recognize and attack cancer cells

See glossary for more terms >, categorized as an ex vivo type of gene-based cell therapy, involves harvesting the person’s own T-cellsa type of white blood cell that is partly in charge of the body's immune response to pathogens

See glossary for more terms > and genetically modifying those cells to create CAR T-cell therapya treatment where a person's T-cells (a part of the immune system) are genetically modified to recognize and attack cancer cells

See glossary for more terms >.17,18 This process instructs T-cells to express an artificial receptor, called a chimeric antigen receptor (CAR). The CAR enables the T-cells to recognize and attack cancer cells, thus becoming CAR T-cell therapy. There are currently several CAR T-cell therapies approved by the FDA to treat different types of cancer.13,17,19

Image of CAR T-cell therapy

The big difference between CAR T-cell therapy and gene therapy is this: CAR T-cell therapy delivers a specific type of cell (T-cells) to a person, while gene therapy delivers genetic material to a person’s cells.1,17,18

Another difference between CAR T-cell therapy and gene therapy is what they are aiming to treat. CAR T-cell therapy has been developed as a tool to fight against cancer since it uses a patient’s T-cells, which are immune cells that have been known to attack cancer cells.17,18

Because there are various types and techniques being explored in gene therapy, it can potentially treat a broad range of diseases at the genetic level beyond just cancer.

OTHER TOPICS YOU MAY BE INTERESTED IN:

Examples of Approved Gene Therapies

Gene Therapy Treatment Process

In vivo  and  ex vivo  approaches In vivo  and
ex vivo  approaches

Keep learning with Genehome

Expand your knowledge with gene therapy and content sent directly to your inbox.
Stay Informed

References

1. National Institutes of Health. Genetics Home Reference. Help me understand genetics. Accessed May 3, 2021. https://medlineplus.gov/download/genetics/understanding/primer.pdf 2. 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 3. Biology Online Dictionary. Monogenic disease. Accessed April 19, 2021. https://www.biologyonline.com/dictionary/monogenic-disease 4. Griffiths AJF, Miller JH, Suzuki DT, et al. An Introduction to Genetic Analysis, 7th edition. W.H. Freeman; 2000. 5. STAT Reports. The STAT guide to viral vectors, the linchpin of gene therapy. STAT News; 2019. 6. Collins M, Thrasher A. Gene therapy: progress and predictions. Proc Biol Sci. 2015;282(1821):770-788. 7. 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 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. Ceasar SA, Rajan V, Prykhozhij SV, Berman J, Ignacimuthu S. Insert, remove or replace: A highly advanced genome editing system using CRISPR/Cas9. Biochimica et Biophysica Acta. 2016 10. Choi J. Huntington’s Outreach Project for Education, at Stanford: Gene Silencing. Accessed July 1, 2021. https://hopes.stanford.edu/gene-silencing/ 11. Balasubramanian S, Habegger L, Frankish A, MacArthur DG, et al. Gene inactivation and its implications for annotation in the era of personal genomics. Genes Dev. 2011;25(1):1-10. 12. 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. 13. 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. 14. Chandler RJ, Venditti CP. Gene therapy for metabolic diseases. Transl Sci Rare Dis. 016;1(1):73-89. 15. Keeler AM, ElMallah MK, Flotte TR. Gene therapy 2017: progress and future directions. Clin Transl Sci. 2017:10(4):242-248. 16. Rees H, Liu D. Base editing: prescision chemistry on the genome and transcriptome of living cells. Nat Rev Genet. 2018;19(12):770-788. 17. American Society of Gene & Cell therapy (ASGCT). Gene and cell therapy FAQs. Accessed July 1, 2021. https://www.asgct.org/education/more-resources/gene-and-cell-therapy-faqs 18. NIH National Cancer Institute. NCI dictionary of cancer terms. CAR T-cell therapy. Accessed July 1, 2021. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/car-t-cell-therapy 19. Almasbak H, Aarvak T, Vemuri MC. CAR T cell therapy: a game changer in cancer treatment. J Immunol Res. 2016;2016:5474602. 20. National Cancer Institute. NCI dictionary of cancer terms: CRISPR-Cas9. Accessed July 1, 2021. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/crispr-cas9 21. Encyclopedia Britannica. Gene editing. Accessed July 1, 2021. https://www.britanica.com/science/gene-editing

Back
to Top