Nanotechnology Could Improve Gene Therapy for Blindness

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Scientists created a lipid nanoparticle capable of delivering mRNA to the retina, opening up an opportunity for the development of additional gene therapies for the eye.

In a study of mice and primates, a lipid nanoparticle has been shown to reach photoreceptors in the eye and successfully deliver mRNA to the retina, according to a study published in Scientific progress. Researchers at Oregon Health & Science University and Oregon State University have developed an approach that uses lipid nanoparticles to deliver strands of messenger ribonucleic acid, or mRNA, into the eye.

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

“More than 250 genetic mutations have been linked to inherited retinal disorders, but only one has an approved gene therapy,” said one of the study’s authors, Renee Ryals, Ph.D., an assistant professor of ophthalmology at 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 may provide more treatment options to prevent blindness. The findings of our research show that lipid nanoparticles could help us do that.”

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

But AAV vectors are small and can only deliver DNA. Lipid nanoparticles do not have the same size limitation 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 author of the study, said the peptide they developed causes mRNA to be precisely delivered to photoreceptors, cells that have so far been unable to target with lipid nanoparticles.

In this study, Ryals, Sahay and colleagues showed that a peptide-coated shell of lipid nanoparticles can be targeted to photoreceptor cells in the retina. To demonstrate a proof of concept, researchers added mRNA with instructions to make a green fluorescent protein. After being injected into the eyes of mice and non-human primates, the retinal tissue of the animals glowed green, showing that the lipid nanoparticle reached the photoreceptors.

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

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