The eyes have it: gene therapy delivered to retina in mice

A 'non-invasive' method for delivering gene therapy into the eye has been developed by US researchers.

The team found that a version of the gene therapy vector adeno-associated virus (AAV) successfully delivered genes to the retina in mice after being injected into the gel-like core of the eye, known as the vitreous humour.

This is less invasive than the current method, where AAVs are injected directly into the retina, and therefore potentially safer.

'Sticking a needle through the retina and injecting the engineered virus behind the retina is a risky surgical procedure', said Professor David Schaffer, director of the Berkeley Stem Cell Center, who led the study. 'Building upon 14 years of research, we have now created a virus that you just inject into the liquid vitreous humor inside the eye, and it delivers genes to a very difficult-to-reach population of delicate cells in a way that is surgically non-invasive and safe'.

Previously, delivering gene therapy into the retina posed a challenge as AAVs are evolved to infect lung cells rather than penetrating tissue. To bioengineer AAV into a form that could migrate to, and penetrate, the retina, the Berkeley team used a technique known as directed evolution.

Directed evolution involved injecting millions of AAVs into the vitreous humour of mouse eyes and selecting only those AAVs that reached retinal cells. Researchers collected these 'successful' vectors, replicated them and repeated the process. This selected the virus particles best adapted to reach and penetrate the retina. After six cycles, the research group sequenced the genomes of the final AAV vectors collected.

Around two-thirds of the evolved AAV vectors were of the same type, which the researchers named 7m8. In mice with hereditary blindness, 7m8 successfully introduced corrective genes to the retina. However, when tested on macaques, vector uptake was patchy, as primates have thicker retinas than mice, but the team hope that further directed evolution may improve uptake.

This method shows promise as a treatment for some forms of hereditary blindness, and could expand the scope of gene therapy. Professor Shaffer predicts these enhanced AAVs could also knock out genes that actively kill retina cells.

Helen May, optometrist and eye health advisor for the Royal National Institute for the Blind, told the Daily Express: 'Clearly it is still at an early stage and more extensive trials are needed to confirm the safety and effectiveness of this kind of treatment'.