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About gene therapy

Educate yourself on the fundamentals

The onset of disease can often be triggered by a single mutation in 1 or more genes.1  Gene therapy aims to treat that disease by modifying a person’s DNA—opening up possibilities for new therapies in the future.2 Review the different therapy types, primary tools and approaches, and delivery methods to establish a foundation of knowledge.

DNA strand icon representing gene therapy

About gene therapy

Educate yourself on the fundamentals

The onset of disease can often be triggered by a single mutation in 1 or more genes.1  Gene therapy aims to treat that disease by modifying a person’s DNA—opening up possibilities for new therapies in the future.2 Review the different therapy types, primary tools and approaches, and delivery methods to establish a foundation of knowledge.

The differences between cell and genetic therapy

Cell and genetic therapy are 2 overlapping fields that take distinct approaches to achieve the same goal: potentially prevent or treat the underlying cause of a disease.3,4 This website primarily focuses on gene therapy, but it is important to understand the differences—and similarities—between the 2 types.

Cell therapy 
Cell therapy is the transplantation of cells to replace or repair damaged tissue and/or cells.It aims to treat a disease by delivering cells responsible for biologic functions in 1 of 2 ways6:

  • Allogeneic cell therapies use donor cells or cultured cell lines, which are administered to a patient4,6-8
  • Autologous cell therapies use a patient’s own cells, which are modified and administered back to the patient6 

Note that autologous cells can be genetically modified via gene-therapy approaches outlined below, with individualized therapies targeting a patient’s own cells.9,10

Human cell icon representing cell therapy  approaches

Gene therapy
Gene therapy is the modification of the cells’ genome via gene addition or gene editing.2,9,11 Gene-therapy methods vary and can include11:

  • Replacing a nonworking gene with a functional gene
  • Inactivating a mutated gene
  • Adding a new or exogenous gene into cells
  • Editing or permanently manipulating a gene
View gene-therapy research
DNA strand icon representing gene therapy  methods

How gene therapy works

Gene therapy has the potential to treat a disease by making changes at the genetic level, including additions or edits to a patient’s cells.See how the 2 main approaches to gene therapy work below.

Gene addition
Gene-addition tools can target faulty genes within a patient’s cells by adding a functional gene into the genome and affecting protein expression.12 The strategic approach for gene addition typically involves:

  • Delivering a new functional gene to a target cell via a viral vector12,13
  • Then, the functional gene either integrates into the host DNA or remains outside the chromosome, both of which can result in functional protein production11-13
Understand gene addition
Plus sign icon representing gene addition tools

Gene editing
Gene-editing tools can disrupt, delete, insert, or correct specific genes within a patient’s cells.14 Strategies that can be used to achieve therapeutic effects include:

  • Inactivating a mutant gene to stop its expression14
  • Correcting a gene mutation back to its original sequence15
  • Inactivating a disease-related gene to turn on an alternative pathway16,17
  • Using a dual-site targeting system to insert or delete a gene16
Explore gene editing
Scissors icon representing gene editing tools

Learn the different gene-therapy approaches

Ready to dig deeper? Explore the gene-therapy tools, techniques, and delivery methods of gene addition and gene editing.

Two DNA strand icons with plus sign representing gene addition and ACGT letters graphic representing DNA code

How gene therapy gets delivered

Gene-therapy delivery methods are generally categorized as ex vivo or in vivo.

Test tube icon representing ex vivo gene therapy

Ex vivo
Cells are removed from the body and isolated; the cells are then modified for the intended genetic change and reintroduced into the patient’s body.18

Target and arrow icon representing in vivo gene  therapy

In vivo
No cells are removed from the body; instead, therapeutic material is delivered to target cells or tissue via viral or nonviral vectors.18

Furthermore, gene therapies can be introduced into the target cells of a patient by several different delivery methods.18 Review the different types of delivery methods—including vectors—along with key examples, details, and considerations below.19

Delivery Methods

Viral vectors:
integrating and nonintegrating viruses

Gene-therapy tools and genetic materials can be packaged into an inactivated virus, which then inserts into the target cells to deliver the genetic materials.18,20 The most commonly used delivery method, viruses can be delivered ex vivo or in vivo and can prompt cells to integrate the genetic material in 2 ways11,18:

  • Via a host cell’s own DNA (integrating viruses such as lentivirus), making them capable of producing permanent insertions11 
  • Remain as extrachromosomal DNA (nonintegrating viruses such as adenovirus)11
    • Immune response may reduce efficiency of viral treatment18
    • Generation of antibodies may preclude use of same virus for a second dose18
    • Insertional mutagenesis may occur when a gene is inserted into a tumor suppressor gene or activates an oncogene if the vectors integrate into the genome at the wrong location18

    Chemical delivery method:
    lipid nanoparticles (LNP)

    Lipid nanoparticles (LNP) are one type of a chemical delivery method. Gene-therapy tools and genetic material can be encapsulated in lipids, which are then taken up by the target cells. This method has been studied across a wide range of drugs and therapies, and features a straightforward process and flexible design.21

      • Immune response to LNP formulations may occur21
      • Therapeutic need for LNP systems with improved potencies21
      • Method is under development for in-vivo therapies and their ability to target nonhepatic tissue types22,23

      Physical delivery method:

      Physical delivery methods can be used to transfer genetic material through the cell membrane by physical force. One example of a physical delivery method is electroporation.19

      Electroporation: Gene-therapy tools and genetic material can be packaged into bacterial plasmids, then electrical pulses create pores in cell membranes that allow for delivery.22,23

        • Potential loss of cell viability24
        • May have limited use for in-vivo delivery due to its impracticality22

        Know the latest gene-therapy disease areas being studied

        Recent advances in gene therapy are stirring excitement in scientists and physicians while raising curiosity in patients and caregivers. Many gene therapies are in active clinical trials, with a range of diseases under research, while several are already being applied as approved treatments for some conditions.25,26

        Explore now
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        References:  1. Arjmand B, Larijani B, Hosseini MS, et al. The horizon of gene therapy in modern medicine: advances and challenges. Adv Exp Med Biol. 2020;1247:33-64. doi:10.1007/5584_2019_463. 2. What is gene therapy? US Food & Drug Administration. Updated July 25, 2018. Accessed April 14, 2023. 3. Gene and cell therapy FAQ’s. American Society of Gene + Cell Therapy. Accessed April 14, 2023. 4. Gupta A, Anderson S. Cell and gene therapy: overview, current landscape and future trends. J Precis Med. Published September 2020. Accessed April 14, 2023. 5. Facts about cellular therapies. Association for the Advancement of Blood & Biotherapies. Accessed April 14, 2023. 6. Mount NM, Ward SJ, Kefalas P, Hyllner J. Cell-based therapy technology classifications and translational challenges. Philos Trans R Soc Lond B Biol Sci. 2015;370(1680):20150017. doi:10.1098/rstb.2015.0017. 7. Pigeau GM, Csaszar E, Dulgar-Tulloch A. Commercial scale manufacturing of allogeneic cell therapy. Front Med. 2018;5:233. doi:10.3389/fmed.2018.00233.  8. Christopher MJ, Petti AA, Rettig MP, et al. Immune escape of relapsed AML cells after allogeneic transplantation. N Engl J Med. 2018;379(24):2330-2341. doi:10.1056/NEJMoa1808777. 9. Dong AC, Rivella S. Gene addition strategies for ß-thalassemia and sickle cell anemia. Adv Exp Med Biol. 2017;1013:155-176. doi:10.1007/978-1-4939-7299-9_6. 10. Naldini L. Ex Vivo gene transfer and correction for cell-based therapies. Nat Rev Genet. 2011;12(5):301-315. doi:10.1038/nrg2985. 11. Bulcha JT, Wang Y, Ma H, Tai PWL, Gao G. Viral vector platforms within the gene therapy landscape. Signal Transduct Target Ther. 2021;6(1):53. doi:10.1038/s41392-021-00487-6. 12. DeWeerdt S. Gene therapy: a treatment coming of age. Pharm J. 2014;293(7831). doi:10.1211/PJ.2014.20066677. 13. Nowakowski A, Andrzejewska A, Janowski M, Walczak P, Lukomska B. Genetic engineering of stem cells for enhanced therapy. Acta Neurobiol Exp. 2013;73:1-18. 14. Khalil AM. The genome editing revolution: review. J Genet Eng Biotechnol. 2020;18(1):68. doi:10.1186/s43141-020-00078-y. 15. Khan SH. Genome-editing technologies: concept, pros, and cons of various genome-editing techniques and bioethical concerns for clinical application. Mol Ther Nucleic Acids. 2019;16:326-334. doi:10.1016/j.omtn.2019.02.027.  16. Cox DBT, Platt RJ, Zhang F. Therapeutic genome editing: prospects and challenges. Nat Med. 2015;21(2):121-131. doi:10.1038/nm.3793. 17. Safari F, Zare K, Negahdaripour M, Barekati-Mowahed M, Ghasemi Y. CRISPR Cpf1 proteins: structure, function and implications for genome editing. Cell Biosci. 2019;9:36. doi:10.1186/s13578-019-0298-7. 18. Goswami R, Subramanian G, Silayeva L, et al. Gene therapy leaves a vicious cycle. Front Oncol. 2019;9:297. doi:10.3389/fonc.2019.00297. 19. Ramamoorth M, Narvekar A. Non viral vectors in gene therapy - an overview. J Clin Diagnostic Res. 2015;9(1):GE01-GE06. doi:10.7860/JCDR/2015/10443.5394; 20. Dunbar CE, High KA, Joung JK, Kohn DB, Ozawa K, Sadelain M. Gene therapy comes of age. Science. 2018;359(6372):eaan4672. doi:10.1126/science.aan4672. 21. Cullis PR, Hope MJ. Lipid nanoparticle systems for enabling gene therapies. Mol Ther. 2017;25(7):1467-1475. doi:10.1016/j.ymthe.2017.03.013. 22. Doudna JA. The promise and challenge of therapeutic genome editing. Nature. 2020;578(7794):229-236. doi:10.1038/s41586-020-1978-5. 23. Seow Y, Wood MJ. Biological gene delivery vehicles: beyond viral vectors. Mol Ther. 2009;17(5):767-777. doi:10.1038/mt.2009.41. 24. Shi J, Ma Y, Zhu J, et al. A review on electroporation-based intracellular delivery. Molecules. 2018;23(11):3044. doi:10.3390/molecules23113044. 25. Gene therapy. Accessed April 14, 2023. 26. Approved cellular and gene therapy products. US Food & Drug Administration. Updated October 26, 2021. Accessed April 14, 2023.