What Is Gene Therapy and How Does It Work

According to the World Health Organization (WHO), gene therapy is defined as the introduction of genetic material into an individual, or the modification of an individual’s genetic material, to achieve a therapeutic objective1


Professional organizations and patient advocacy groups provide online resources to inform patients as to what gene therapy is and how it works to make informed decisions2,3

In this section, we will hear from experts in the field of gene therapy who will discuss their approaches to talking with patients and families about gene therapy.

Misconceptions: Transmission to the Next Generation

There are two main categories of gene therapy:4


Somatic Gene Therapy

Somatic gene therapy involves the alteration of genetic materials in diploid cells, replacing mutated or missing disease-causing genes with functional normal ones, inhibiting expression of abnormal genes, or adding a new gene4,5

  • Effects are limited to the patient and targeted to specific cells or tissue in their body4,6 
  • In somatic gene therapies, the altered genetic material is not passed on to the patient’s progeny4

Germline Gene Therapy

Germline gene therapy involves the direct manipulation of germline cells, including egg and sperm cells4,6

  • Some gametes may carry the corrected gene and, therefore, this genetic manipulation has the potential of being transferred to the patient’s progeny4
  • Due to ethical concerns, germline gene therapy is banned or restricted in certain countries4,6

Patients and families can be informed that only somatic gene therapy is used in clinical practice and is typically not transmitted to the next generation4,6

Concerns Related to the Viral Vector

Viral vectors are naturally occurring viruses that have been modified so that the original viral genes are replaced with the transgene of interest4,7

The removal of viral genes means that virulence is decreased, replication can be affected, and the viral vector will not trigger the same immune response as the wild-type virus4,7,8

Example: Concerns related to the viral vector

  • Adeno-associated viral vectors (AAVs) are considered nonpathogenic and have been able to infect various target tissues. Thus, AAVs are widely used in gene therapy clinical trials9,10
    • All AAV serotypes are categorized by the National Institutes of Health (NIH) as Risk Group 1, indicating they are not infectious or associated with disease in humans9
  • A number of AAV gene therapies that have favorable benefit–risk profiles, such as voretigene neparvovec-rzyl, have been approved for use11-13


  1. Genomics and world health: report of the Advisory Committee on Health Research. World Health Organization. Accessed October 6, 2021. http://apps.who.int.iris/handle/10665/42453
  2. Patient education. American Society of Gene and Cell Therapy. Accessed October 21, 2021. https://patienteducation.asgct.org/about-asgct/overview
  3. Gene therapy basics. American Society of Gene and Cell Therapy. Accessed February 2, 2021. https://patienteducation.asgct.org/gene-therapy-101/gene-therapy-basics
  4. Nayerossadat N, Maedeh T, Ali PA. Viral and nonviral delivery systems for gene delivery. Adv Biomed Res. 2012;1:27. doi:10.4103/2277-9175.98152
  5. What is gene therapy? MedlinePlus. Accessed October 27, 2021. https://medlineplus.gov/genetics/understanding/therapy/genetherapy
  6. What are the ethical issues surrounding gene therapy? MedlinePlus. Accessed October 6, 2021. https://medlineplus.gov/genetics/understanding/therapy/ethics/
  7. Nayak S, Herzog RW. Progress and prospects: immune responses to viral vectors. Gene Ther. 2010;17(3):295-304. doi:10.1038/gt.2009.148. Published correction appears in Gene Ther. 2010;17(2):294.
  8. Wang D, Gao G. State-of-the-art human gene therapy: part I. Gene delivery technologies. Discov Med. 2014;18(97):67-77.
  9. Al-Zaidy SA, Mendell JR. From Clinical Trials to Clinical Practice: Practical Considerations for Gene Replacement Therapy in SMA Type 1. Pediatr Neurol. 2019;100:3-11. doi:10.1016/j.pediatrneurol.2019.06.007
  10. Dong Z, Ye L, Yang Z, et al. Balanced Chromosomal Rearrangement Detection by Low-Pass Whole-Genome Sequencing. Curr Protoc Hum Genet. 2018;96:8.18.1-8.18.16. doi:10.1002/cphg.51
  11. Luxturna® [prescribing information]. Philadelphia, PA: Spark Therapeutics, Inc; 2017.
  12. Ginn SL, Amaya AK, Alexander IE, Edelstein M, Abedi MR. Gene therapy clinical trials worldwide to 2017: An update. J Gene Med. 2018;20(5):e3015. doi:10.1002/jgm.3015. Published correction appears in J Gene Med. 2019;21(9):e3124.
  13. Schwartz M, Likhite S, Meyer K. Onasemnogene abeparvovec-xioi: a gene replacement strategy for the treatment of infants diagnosed with spinal muscular atrophy. Drugs Today (Barc). 2021;57(6):387-399. doi:10.1358/dot.2021.57.6.3264117