Researchers have engineered a new adeno-associated virus that could greatly expand gene therapy to help restore sight to patients with blinding diseases like retinitis pigmentosa and macular degeneration.

Over the last six years, several teams of scientists have successfully treated people with a rare inherited eye disease by injecting a virus with a normal gene directly into the retina of an eye with a defective gene. Despite the invasive process, the virus with the normal gene was not capable of reaching all the retinal cells that need fixing.

“Sticking a needle through the retina and injecting the engineered virus behind the retina is a risky surgical procedure,” explained Prof David Schaffer of the University of California, Berkeley, senior author of a paper published in the journal Science Translational Medicine.

“But doctors have no choice because none of the gene delivery viruses can travel all the way through the back of the eye to reach the photoreceptors – the light sensitive cells that need the therapeutic gene.”

Prof Schaffer generated around 100 million variants of adeno-associated virus – each carrying slightly different proteins on its coat – from which he and his colleagues selected five that were effective in penetrating the retina.

They then used the best of these, labeled 7m8, to transport genes to cure two types of hereditary blindness for which there are mouse models: X-linked retinoschisis, which strikes only boys and makes their retinas look like Swiss cheese; and Leber’s congenital amaurosis. In each case, when injected into the vitreous humor, the engineered virus delivered the corrective gene to all areas of the retina and restored retinal cells nearly to normal.

“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. It’s a 15-minute procedure, and you can likely go home that day.”

The engineered adeno-associated virus works far better than current therapies in rodent models of two human degenerative eye diseases, and can penetrate photoreceptor cells in the eyes of monkeys.

“The team is now collaborating with physicians to identify the patients most likely to benefit from this gene-delivery technique and, after some preclinical development, hope soon to head into clinical trials,” Prof Schaffer said.

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Bibliographic information: Deniz Dalkara et al. 2013. In Vivo–Directed Evolution of a New Adeno-Associated Virus for Therapeutic Outer Retinal Gene Delivery from the Vitreous. Sci Transl Med, vol. 5, no. 189; doi: 10.1126/scitranslmed.3005708