Leber congenital amaurosis (LCA) is an inherited retinal disease. Many distinct gene mutations are related to LCA; these are often found in both copies of the gene in each chromosome of the homologous chromosome pair (biallelic mutations). LCA's clinical symptoms are diverse, including low light sensitivity (photophobia), altered shape of the eyes (nyctalopia), outward bulging of the cornea (keratoconus), cataracts, and more. However, four clinical features are described in all forms of LCS: early and pronounced visual loss, lack of pupillary light reflex (amaurotic pupils), nystagmus, and a lack of electrical signs on electroretinogram. Nystagmus is generally the first sign, apparent at the age of 6 weeks. LCA is a form of retinal dystrophy without major systemic implications.

One LCA type, LCA type 2 (LCA2), is caused by the biallelic mutation of the gene coding for the retinal pigment epithelium-specific 65 kDa (RPE65) protein.

In LCA2 patients with viable retinal cells, the lack of functional RPE65 can, in principle, be overcome through the supply of an artificial gene coding for this protein. The gene is packed inside viral particles that are surgically injected into the patient’s retina. Viral particles will deliver the gene into retinal cells, which will produce RPE65, to restore the visual cycle. The preferred viral particles are adeno-associated viruses. These lack pathogenicity and cause only minor immune responses. They can also maintain regular levels of therapeutic gene expression in non-dividing cells. The outcome of gene therapy in LCA2 patients is frequently assessed using a multi-luminance mobility test.

The eye has unique features that make it an ideal site for gene therapy interventions. It is easily accessible via injection or surgery. As retinal cells stop dividing about 12 months after birth, a single gene therapy intervention is, in principle, sufficient after this age. As the eye is a relatively small compartment, small treatment dosages are also, in principle, sufficient. Moreover, one eye can serve as a control of the other. The physical isolation of the eye from the rest of the body decreases the risk of affecting other parts of the body, minimizing side effects. The eye's specific immune status makes it less predisposed to immune reactions than most human organs. Its accessibility also facilitates the assessment of therapeutic outcomes by non-invasive medical procedures.