UC Berkeley Researchers Developing Improved Optogenetic Therapy

July 10, 2015

While two commercially backed optogenetic therapies for restoring vision are poised to move into human studies, a Foundation-funded research team led by John Flannery, Ph.D., at the University of California, Berkeley, is developing an optogenetic alternative that may provide additional advantages.

Optogenetics is of strong interest to retinal researchers because it holds promise for restoring vision for people who are completely blind due to the loss of photoreceptors from retinal diseases like retinitis pigmentosa, Usher syndrome and age-related macular degeneration. The treatment approach involves delivery of proteins or chemicals that provide light-sensitivity to surviving retinal cells. Also, it works regardless of the mutated gene causing the vision loss.

The companies GenSight Biologics and RetroSense Therapeutics are preparing for human studies for their optogenetic therapies, which produce light-sensing proteins derived from blue-green algae.

In a research paper published in Molecular Therapy, Dr. Flannery reports that his approach involves delivery of a gene that expresses rhodopsin — a light-sensitive protein naturally occurring in human photoreceptors — in adjacent bipolar cells. Because they survive even after photoreceptors have degenerated, bipolar cells are a desirable target. Dr. Flannery’s treatment restored vision in blind mice during a pre-clinical trial, so he is cautiously optimistic about his approach.

“We think of it as simply moving the retina’s natural light-sensitive protein, rhodopsin, down to the next cell layer,” says Dr. Flannery.

He explains that the rhodopsin therapy may offer advantages over other alternatives. Namely, it shows potential for working in lower levels of light than algae-derived proteins. Furthermore, he believes it may be a safer alternative, because rhodopsin is naturally expressed in the eye.

“Our hope was that rhodopsin would continue to operate at lower, more natural light levels and adapt to a wider range of lighting intensities than other optogenetic treatments,” he says. “We found that other approaches may require the patient to use special glasses or goggles to modify the light intensity.”

Dr. Flannery acknowledges that his therapy is still a long way from being ready for a clinical trial. Much more lab research is needed before it can be studied in humans.

“While optogenetic therapies will likely soon be in the clinic, it doesn’t mean we stop improving upon them to have better options available down the road,” says Stephen Rose, Ph.D., chief research officer at the Foundation. “It is important that we keep the pipeline full.”

Dr. Rose notes that, in addition to funding Dr. Flannery’s emerging treatment, the Foundation has also provided support for development of the GenSight and RetroSense therapies.

GenSight’s optogenetic treatment involves production of light-sensing proteins in bipolar cells. RetroSense is targeting ganglion cells, which also persist after photoreceptors have degenerated. 

In all of the treatments, a human-engineered virus known as an adeno-associated virus, or AAV, is used to deliver therapeutic genes to the retinal cells.