Gene therapy approaches.

Developments in gene therapy vector systems and technologies.

Gene therapy research highlights the importance of genetic testing.

The use of vectors in gene therapy.

There are multiple approaches to gene therapy research, including inserting a healthy copy of the mutated gene, inactivating a mutated gene that is functioning improperly, or introducing a new gene into a target tissue, such as the retina, in the body.1,2

There are two potential methods of delivering the genetic material:

  • In vivo gene therapy: directly introduces the gene into the patient’s eye using a vector, which is the only feasible method of accessing these particular cells of interest.3
  • Ex vivo gene therapy: harvests cells from the patient, genetically modifies them, and returns them to the patient. A few cell types may lend themselves well to ex vivo gene therapy, but many do not.3
2 delivery methods

Adapted from National Institutes of Health 2001. Use of genetically modified stem cells in experimental gene therapies.4

Video: The delivery.


An ideal vector.

As extensively evaluated in clinical trials, the outcome of gene therapy relies heavily on both the vector and the efficient delivery of the gene to the target cell.3

An ideal vector should be able to protect a transgene against degradation by nucleases, allow transport of the transgene into the nucleus of target cells, and have minimal inflammatory effects. Viruses are used because they can efficiently gain access to host cells to exploit the cellular machinery and facilitate their replication.5-7

Because of their biological evolution and characteristics, viruses are the preferred transporter for most gene therapy applications.<sup>7</sup>
Because of their biological evolution and characteristics, viruses are the preferred transporter for most gene therapy applications.<sup>7</sup>

Viruses used as vectors.

The adeno-associated virus (AAV) is a small, nonenveloped virus that packages a linear, single-stranded DNA genome. It usually remains within the target tissues as episomal entities, although integration into the host cell genome can rarely occur.5,7,8

Why AAV?

AAV is unique because it is not known to cause disease in humans and has low potential for inflammation. For these reasons, they are among the most frequently used viral vectors for gene therapy research, as demonstrated in a number of successful preclinical and clinical studies.5,8,9

The adenovirus (Ad) is a nonenveloped virus that contains a linear, double-stranded DNA genome. It has one of the largest capacities for delivering transgenes, is episomal, and offers minimal risk of insertional mutagenesis. Ad has a high inflammatory potential.9

The lentivirus (LV) is an enveloped retrovirus containing a positive-sense, single-stranded RNA genome. It integrates its genome into the chromosomes of target cells and can provide long-term expression in dividing cells. LV has a low inflammatory potential.7,9

Illustrations adapted from Kotterman 2014 and Rastall 2015.10,11

Video: See how AAVs target selected tissues.


We are committed to helping you help your patients.

In support of the IRD community, Spark Therapeutics provides resources to educate your patients about the science of gene therapy research and importance of genetic testing.

Resources for patients


  1. National Institutes of Health, U.S. Library of Medicine. Genetics Home Reference. What is gene therapy? Published August 2017, accessed August 22 2017.
  2. American Society of Gene & Cell Therapy. Gene therapy and cell therapy for diseases. Accessed November 10 2016.
  3. High KA. The Jeremiah Metzger Lecture: gene therapy for inherited disorders: from Christmas disease to Leber’s amaurosis. Trans Am Clin Climatol Assoc. 2009;120:331-359.
  4. National Institutes of Health. Use of genetically modified stem cells in experimental gene therapies. Accessed March 6, 2017.
  5. dos Santos Coura R, Nardi NB. A role for adeno-associated viral vectors in gene therapy. Gene Mol Biol. 2008;31(1):1-11.
  6. Gehrie EA, Bersenev A, Bruscia E, Krause D, Schulz WL. Gene therapy applications to transfusion medicine. In: Simon TL, McCullough J, Snyder EL, Solheim BG, Strauss RG, eds. Rossi’s Principles of Transfusion Medicine. 5th ed. Hoboken, NJ: Wiley-Blackwell; 2016:452-455.
  7. Thomas CE, Ehrhardt A, Kay MA. Progress and problems with the use of viral vectors for gene therapy. Nat Rev Genet. 2003;4(5):346-358.
  8. Daya S, Berns KI. Gene therapy using adeno-associated virus vectors. Clin Microbiol Rev. 2008;21(4):583-593.
  9. Trapani I, Puppo A, Auricchio A. Vector platforms for gene therapy of inherited retinopathies. Prog Retin Eye Res. 2014;43:108-128
  10. Kotterman MA, Schaffer DV. Engineering adeno-associated viruses for clinical gene therapy. Nat Rev Genet. 2014;15(7):445-451.
  11. Rastall DPW, Amalfitano A. Recent advances in gene therapy for lysosomal storage disorders. Appl Clin Genet. 2015;8:157-169.