Scientists at Oregon State University College of Pharmacy have demonstrated in animal models the potential to use lipid nanoparticles and messenger RNA, the technology behind COVID-19 vaccines, to treat blindness associated with rare genetic disease.
Researchers have developed nanoparticles capable of penetrating the neural retina and delivering mRNA to photoreceptor cells whose proper functioning makes 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 today in Scientists progress.
Scientists overcame what had been the main limitation of using lipid nanoparticles, or LNPs, to carry genetic material for vision therapy – by getting them to reach the back of the eye, where the retina.
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 provides instructions for cells to make a particular 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 in the body. As a therapy for vision disorders resulting from inherited retinal degeneration, or IRD, mRNA would instruct photoreceptor cells – defective due to a genetic mutation – to make proteins necessary for sight.
IRD encompasses a group of disorders of varying severity and prevalence that affect one in a few thousand people worldwide.
Scientists have shown, in research involving mice and non-human primates, that peptide-equipped LNPs are able to cross barriers in the eye and reach the neural retina, where light is transformed into electrical signals that the brain converts into images.
“We have identified a new set of peptides that can reach the fundus,” Sahay said. “We used these peptides to act as zip codes to deliver nanoparticles carrying genetic material to the intended address in the eye.”
“The peptides we discovered can be used as targeting ligands directly conjugated to silent RNAs, small molecules for therapeutic purposes, or as imaging probes,” Herrera-Barrera added.
Sahay and Ryals received a $3.2 million grant from the National Eye Institute to continue studying the promise of lipid nanoparticles in the treatment of hereditary blindness. They will lead research into using LNPs to provide a gene-editing tool that might remove bad genes in photoreceptor cells and replace them with properly functioning genes.
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 ability compared to LNPs and it can trigger an immune system response,” Sahay said. “It also doesn’t work fantastically to keep expressing the 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 regarding LNPs to develop an improved gene-editor delivery system.”
The peptide-guided LNP study was funded by the National Institutes of Health. College of Pharmacy professors 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 bioengineering student Nick Jacomino at the College , also participated in the research for Oregon State. of engineering who graduated in 2020.
