
10/19/2021
PITTSBURGH – A novel computational platform developed by researchers from the University of Pittsburgh School of Medicine identifies top-performing viral vectors that could deliver gene therapies to the retina with maximum efficiency and precision.
The technology, described in a paper published today in the journal eLife, streamlines development of gene therapy approaches for the treatment of genetic blinding disorders. The approach saves precious time and resources by speeding up identification of suitable gene-carrying candidates able to deliver therapy to an affected part of the retina with astounding accuracy.

Even though blinding genetic disorders that affect the retina are considered rare, approximately 1 in every 3,000 people worldwide carries one or more copies of broken genes that cause retinal degeneration and loss of vision. For centuries, many people with inherited blindness were all but guaranteed to spend a portion of their lives in darkness.
Now, with several gene therapies already on the market in Europe and the U.S., and dozens more entering clinical trials, hope for people with inherited blindness is within reach, but a key obstacle remains: ensuring that vectors, or inactivated viruses carrying the therapeutic genetic code, enter the exact cells that scientists are targeting. The retina is composed of hundreds of millions of cells that are arranged into a series of layers, so precisely targeting the vector to a specific location within that universe is not a trivial task.

The traditional approach of evaluating AAVs is painstakingly slow, requiring several years and many experimental animals. It also is not very precise, since it doesn’t directly measure if AAVs not only entered the cells but also delivered their gene therapy cargo.
In contrast, scAAVengr uses single-cell RNA sequencing, which detects if the cargo arrives at its destination safely. And with scAAVengr, that process takes months, not years.
The platform’s uses aren’t just limited to the retina—the researchers showed that it works just as well for the identification of AAVs that target other tissues, including the brain, heart and liver.
“A rising tide lifts all boats, and we hope that this technology propels gene therapy treatments not just in the field of vision restoration but for other purposes,” said Byrne. “Rapidly developing fields of gene editing and optogenetics all rely on efficient gene delivery, so the ability to quickly and strategically choose the delivery vectors would be an exciting leap forward.”
Other authors of this research include Bilge Öztürk, Ph.D., Molly Johnson, B.S., Serhan Turunç, Ph.D., Jing He, B.S., Sara Jabalameli, P.S.M., Zhouhuan Xi, B.S., William R. Stauffer, Ph.D., and José-Alain Sahel, M.D., all of Pitt; Michael Kleyman, Ph.D., and Andreas Pfenning, Ph.D., both of Carnegie Mellon University; Meike Visel, Ph.D., David Schaffer, Ph.D., and John Flannery, Ph.D., all of the University of California Berkeley; Valérie Dufour, Ph.D., Simone Iwabe, Ph.D., Felipe Pompeo Marinho, Ph.D., and Gustavo Aguirre, Ph.D., all of the University of Pennsylvania.
This research was supported by the National Institutes of Health (F32EY023891, R24EY-022012, R01EY017549, P30EY001583, UG3MH120094, DP2MH113095), The UPMC Immune Transplant and Therapy Center, Foundation Fighting Blindness, Ford Foundation, Research to Prevent Blindness and the Van Sloun Fund for Canine Genetic Research.
PHOTO INFO: (click images for high-res versions)
Top:
CREDIT: Joshua Franzos
CAPTION: Leah Byrne, Ph.D., assistant professor of ophthalmology, University of Pittsburgh School of Medicine.
Bottom:
CREDIT: Leah Byrne
CAPTION: Cells in the periphery of the retina infected with AAV carrying a green fluorescent protein. The cells’ nuclei are labeled blue.