Inherited retinal diseases and gene therapy: A good fit

Diagram showing how gene therapy is administered to the eye.

Gene therapy is bringing treatment options to patients who previously had none.7

Gene therapy is the delivery of genetic material into cells via a vector to treat a genetic disease.1


There are different types of gene therapy that can address the underlying cause of a genetic disease2:

  • Gene augmentation: introducing an additional copy of an existing gene to restore or enhance the normal function.2
  • Gene inactivation: blocks the expression of a mutated gene that is causing the disease state.2,3
  • Therapeutic gene delivery: introduces a specific gene that can cause selective cell death, i.e. causing cells to produce a cell surface protein recognised by antibodies.2,3
  • Gene editing: modifying DNA in the cell to correct specific mutations, e.g. CRISPR/Cas9.2,3
Image showing how genetic material is transferred in gene therapy.

Image to illustrate the components of gene therapy.



Viruses are often used as vectors

  • Common virus vectors: adeno-associated virus (AAV), adenovirus and lentivirus.2
  • They can deliver the gene by infecting the cell.1–3
  • Modified vectors lack viral DNA and do not replicate in host.1
  • They are engineered to target various host cell/tissue types.1–3
  • The viral capsid serotype determines the cell types the vector will preferentially target.1–3
  • For example, the serotype AAV2 targets several cell types including retinal epithelial cells (RPE).1–3


In ophthalmology, modified AAV is commonly used as a gene therapy vector2,6 because:

  • It has low potential to cause an immune response.2,5
  • It has been shown to be safe and effective in preclinical and clinical studies to date.1



  • The gene is episomal (circular), and it does not incorporate into the host DNA and cannot be passed onto offspring.1,6
  • The genetic material inside the vector generally contains a gene of interest and DNA elements that allow the gene to be expressed.1,6

>270 genes have identified mutations associated with IRDs.8

The eye is an easily accessible, highly compartmentalised and immune-privileged organ.5


There are multiple ongoing gene therapy trials for IRDs utilising AAV, lentivirus and other gene technology, including for6:

  • Stargardt disease
  • Achromatopsia
  • X-linked retinoschisis
  • Choroideremia
  • X-linked retinitis pigmentosa
  • Leber’s hereditary optic neuropathy

Genetic testing is essential to confirm your patient’s eligibility for gene therapy.

With the help of genetic testing, gene therapy can be targeted to address IRDs caused by single gene mutations.5,9

• IRDs are often monogenic and >270 genes are implicated across a variety of phenotypes.5,9,10

Venn diagram highlighting how different gene mutations can be identified for gene therapy through the use of genetic testing


The American Academy of Ophthalmology® 2014 guidelines:

Genetic tests can improve the accuracy of diagnoses and prognoses, can improve the accuracy of genetic counseling, can reduce the risk of disease occurrence or recurrence in families at risk, and can facilitate the development and delivery of mechanism-specific care.10

Give patients with IRDs the opportunity for a complete diagnosis with a clinical and genetic test.10


IRD, inherited retinal dystrophy; RPE, retinal pigment epithelium.


  1. Naso M et al. BioDrugs 2017;31:317–334.
  2. Trapani I et al. Prog Retin Eye Res 2014;43:108–128.
  3. Sahel JA, Roska B. Annu Rev Neurosci 2013;36:467–488.  
  4. Rodrigues GA et al. Pharm Res 2018;36(2):29.  
  5. Leroy B et al. EyeNet Supplement 2018; July. https://www.aao.org/Assets/bebfbaef-a092-45b0-9883-c563331546ae/636649294795430000/july-2018-eyenet-supplement-pdf?inline=1 (Accessed October 2022).
  6. Liu M et al. Br J Ophthalmol 2011;95(5):604–612.
  7. Russell S et al. Lancet 2017;390(10097):849–860.
  8. RetNet. https://sph.uth.edu/retnet/sum-dis.htm#A-genes (Accessed October 2022).  
  9. Verbakel SK et al. Prog Retin Eye Res 2018;66:157–186.
  10. American Academy of Ophthalmology®, IRD Clinical Statement. 2016. https://www.aao.org/clinical-statement/recommendations-on-clinical-assessment-of-patients (Accessed October 2022).
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UK | October 2022 | 236128

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