OSU Research in Hereditary Blindness

Photo: OSU

Oregon State University College of Pharmacy scientists have demonstrated in animal models the possibility of using lipid nanoparticles and messenger RNA, the technology underlying COVID-19 vaccines, to treat blindness associated with a rare genetic condition.

Researchers have developed nanoparticles that are able to penetrate the neural retina and deliver messenger RNA to the photoreceptor cells whose proper function makes vision possible.

The study, which was led by Oregon State University Associate Professor of Pharmaceutical Sciences Gaurav Sahi, Oregon State doctoral student Marco Herrera-Barrera, and Oregon Health & Science University Associate Professor of Ophthalmology Rene Ryals, is published today in Science Advances.

The scientists overcame what had been the main limitation of using lipid nanoparticles, or LNPs, to transport genetic material for the purpose of vision therapy — getting it to the back of the eye, where the retina is located.

Lipids are fatty acids and similar organic compounds including many natural oils and waxes. Nanoparticles are small pieces of material ranging in size from one to 100 billionths of a meter. Messenger RNA delivers instructions to cells to make a specific protein.

With coronavirus vaccines, mRNA carried by LNPs instructs cells to make a harmless piece of the virus spike protein, which triggers an immune response from the body. As a treatment for visual impairment caused by inherited retinal degeneration, or IRD, the mRNA would instruct photoreceptor cells — defective due to a genetic mutation — to manufacture proteins needed for vision.

IRD includes a group of disorders of varying severity and prevalence affecting about one in every few thousand people worldwide.

The scientists showed, in research involving mice and non-human primates, that LNPs equipped with peptides were able to pass through barriers in the eye and reach the neural retina — where light is converted into electrical signals that the brain converts into images.

“We identified a new group of peptides that can reach the back of the eye,” Sahi said. “We used these peptides to act as zip codes to deliver nanoparticles carrying genetic material to the intended address within the eye.”

“The peptides we discovered can be used to target ligands directly associated with RNA silencing, small molecules for therapy or as imaging probes,” added Herrera-Barrera.

Sahay and Ryals have received a $3.2 million grant from the National Eye Institute to further study the promise of lipid nanoparticles in treating hereditary blindness. They will lead research in using LNPs to deliver a gene-editing tool that can delete bad genes in photoreceptor cells and replace them with properly functioning genes.

The research aims to develop solutions to the limitations associated with the current primary means of delivering gene editing: a type of virus known as an adeno-associated virus, or AAV.

“AAVs have a limited encapsulation capacity compared to LNPs and can stimulate an immune system response,” Sahi said. “It also does not do fantastically well at continuing to express enzymes that the editing tool uses as molecular scissors to make cuts in the DNA to be edited. We hope to use what we have learned so far about LNPs to develop an improved gene editor delivery system.”

The peptide-guided LNP study was funded by the National Institutes of Health. Also involved in the research for Oregon State were College of Pharmacy faculty members Oleh Taratola and Conroy Sun, postdoctoral researchers Milan Gautam and Mohit Gupta, doctoral students Anthony Guzik and Madeline Landry, research assistant Chris Acosta, and undergraduate Nick Giacomeno, a bioengineering student in the college. of engineering who graduated in 2020.

Source: Oregon State University

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