Gene therapy’s had a bad reputation over the years, but some gene-based treatments have been successful. One type of therapy, for degeneration of the retina, has been somewhere in the middle: Injecting a gene directly into the retina that can aid against eye disease. This procedure requires a hospital stay and general anesthesia, and can often damage the retina itself (thus defeating the point of the therapy).
But other eye drugs are often delivered into the eye’s vitreous humor (the fluid inside the eyeball), which is a much safer procedure that can be conducted in a doctor’s office. So, what if the gene for retinal degeneration could be delivered that way?
The problem was that the virus that usually delivers to the gene to its destination, called an Adeno-associated virus or AAV, was never very good at puncturing through dense tissues like the retina. It works fine for thin lung tissue, or even other areas, but not the retina. So, researchers at the University of California, Berkeley, started looking for versions of AAV that could penetrate into the retina.
And as they reported in Science Translational Medicine, they found those versions. Testing several types of AAV on mice, a tiny percentage made their way into mouse retinas. By collecting those versions and amplifying the growth of them in the lab, they finally isolated about 48 AAV variants for genetic sequencing (up to now, by the way, is now traditionally breeding for traits is done). Two thirds of those variants, it turns out, were the same. Now, thanks to what they called “directed evolution,” the scientists had their viral delivery system for retinal gene therapy.
The scientists still don’t know how or why these variants work better at penetrating the retina. Perhaps the gene sequencing studies will provide clues.
Sources: The Scientist
Dalkara, D., Byrne, L., Klimczak, R., Visel, M., Yin, L., Merigan, W., Flannery, J., & Schaffer, D. (2013). In Vivo-Directed Evolution of a New Adeno-Associated Virus for Therapeutic Outer Retinal Gene Delivery from the Vitreous Science Translational Medicine, 5 (189), 189-189 DOI: 10.1126/scitranslmed.3005708
eye degeneration,adeno-associated viruses,gene therapy research article