Safety and toxicology of ocular gene therapy with recombinant AAV Vector rAAV.hCNGA3 in non-human primates.

The purpose of this study was to examine the toxicity and side effects of a recombinant AAV8 vector, aimed to treat CNGA3-linked achromatopsia, after a single subretinal administration in cynomolgus macaques. Animals were followed in two studies: a 13-week study with 22 animals and a 28-day study with 12 animals. Both groups were divided into subgroups receiving either vehicle only, a low (1x1011 vector genomes (vg)), or a high dose (1x1012 vg) of rAAV.hCNGA3. In the 13-week study, an extra group received single high dose intravitreal injections. Here we show the group results of the histological examinations carried out after necropsy from the 28-day study, the retinal functional (ERG) in the 13-week study and clinical observations from both studies. Treatment related adverse effects were not found and parameter changes were mostly related to the surgical procedure. The treatment of achromatopsia with rAAV.hCNGA3 is therefore deemed safe to apply to humans.