Nanotechnology Could Improve Gene Therapy for Blindness

A lipid nanoparticle has been shown in a study of mice and primates to reach photoreceptors in the eye and successfully deliver mRNA to the retina, according to a study published in Science Advances. Researchers with Oregon Health & Science University and Oregon State University have created an approach that uses lipid nanoparticles to deliver strands of messenger ribonucleic acid, or mRNA, inside the eye.

This research opens the door for the development of additional gene therapies to treat eye disease. Lipid nanoparticles can be used with mRNA that create proteins to edit genes that lead to blindness.

Renee Ryals, Ph.D.

“More than 250 genetic mutations have been linked to inherited retinal diseases, but only one has an approved gene therapy,” one of the study authors, Renee Ryals, Ph.D., an assistant professor of ophthalmology in the OHSU School of Medicine and a scientist at the OHSU Casey Eye Institute, said in a press release. “Improving the technologies used for gene therapy can provide more treatment options to prevent blindness. Our study’s findings show that lipid nanoparticles could help us do just that.”

The only gene therapy approval to treat a disease of the eye is Luxturna (voretigene neparvovec-rzyl), which was approved by the FDA in December 2017, to treat children and adult patients with an inherited form of blindness. Developed by Spark Therapeutics, Luxturna uses a modified version of the adeno-associated viral (AAV) to deliver the biallelic RPE65 gene.

But AAV vectors are small and can only delivery DNA. Lipid nanoparticles don’t have the same restriction of size and can be used to deliver mRNA, which could prevent off-target effects.

Gaurav Sahay, Ph.D., an associate professor in the OSU College of Pharmacy who also has a joint research appointment at the OHSU Casey Eye Institute and another study author, said they peptide they developed ensures mRNA is precisely delivered to photoreceptors, cells that haven’t been able to target with lipid nanoparticles until now.

In this study, Ryals, Sahay and colleagues showed that a peptide-covered lipid nanoparticle shell can be directed toward photoreceptor cells in the retina. To demonstrate a proof of concept, researchers included mRNA with instructions to make a green fluorescent protein. After injecting this into the eyes of mice and nonhuman primates, the animals’ retinal tissue glowed green, which demonstrated that the lipid nanoparticle reached the photoreceptors.

The researchers are working to develop a therapy with mRNA that carries the code for gene-editing molecules with a $3.1-million grant from the National Eye Institute of the National Institutes of Health.