Oregon State University researchers develop new treatment for hereditary blindness

PORTLAND, Ore. — Oregon State University College of Pharmacy scientists have demonstrated in animal models the potential of using lipid nanoparticles and messenger RNA, the technology backing COVID-19 vaccines, to treat blindness associated with a rare genetic condition, according to a release from the university.

Researchers developed nanoparticles that are able to penetrate the neural retina and transmit mRNA to the photoreceptor cells, making vision possible.

The study, led by OSU associate professor of pharmaceutical sciences Gaurav Sahay, Oregon State doctoral student Marco Herrera-Barrera and Oregon Health & Science University assistant professor of ophthalmology Renee Ryals, was published on Wednesday in Science Advances.

According to the release, scientists had a main limitation of getting the lipid nanoparticles (LNPs), used to carry genetic material, to reach 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 tiny pieces of material ranging in size from one- to 100-billionths of a meter. Messenger RNA delivers instructions to cells for making a particular protein.

In research using mice specimen and non-human primates, scientists showed that LNPs equipped with peptides were able to pass through the natural barriers in the eye and reach the neural retina, where light is turned into electric signals that alert the brain to convert images.

“We identified a novel set of peptides that can reach the back of the eye,” Sahay said. “We used these peptides to act as zip codes to deliver nanoparticles carrying genetic materials to the intended address within the eye.”

"The peptides that we have discovered can be used as targeting ligands directly conjugated to silencing RNAs, small molecules for therapeutics or as imaging probes,” Herrera-Barrera added.

Sahay and Ryals are expected to lead research into using LNPs in order to deliver a gene editing tool that could remove "bad genes" in the photoreceptor cells and replace them with correctly functioning genes.

This comes after Sahay and Ryals received a $3.2 million grant from the National Eye Institute to continue studying the potential of lipid nanoparticles and the role they play in treating hereditary blindness.

According to the release, the research aims to develop solutions for the limitations associated with the current primary means of delivery for gene editing: a type of virus known as adeno-associated virus, or AAV.

“AAV has limited packaging capacity compared to LNPs and it can prompt an immune system response,” Sahay said. “It also doesn’t do fantastically well in continuing to express the enzymes the editing tool uses as molecular scissors to make cuts in the DNA to be edited. We’re hoping to use what we’ve 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 participating in the research for Oregon State were College of Pharmacy faculty Oleh Taratula and Conroy Sun, postdoctoral researchers Milan Gautam and Mohit Gupta, doctoral students Antony Jozic and Madeleine Landry, research assistant Chris Acosta and undergraduate Nick Jacomino, a bioengineering student in the College of Engineering who graduated in 2020.

For more information about Oregon State University College of Pharmacy, visit their website.