Treatment with lipid Nanoparticles, Genetic therapy, Fluorescent staining
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Researchers at Oregon Health & Science University have applied lipid nanoparticles previously used to deliver COVID-19 vaccines as a new approach to gene therapy which could improve the treatment of inherited types of blindness.

Five years ago, the FDA approved the first adeno-associated virus (AAV) based gene therapy to treat an inherited form of blindness, helping many patients improve their vision. Despite its effectiveness, AAV therapy has its limitations due to the virus’s small size and inability to carry large gene-editing machinery for complex mutations.

Reporting in Science Advances, a team of researchers at Oregon Health & Science University have developed a new gene therapy approach using lipid nanoparticles coated with a peptide to deliver strands of mRNA to light-sensitive cells in the eye, called photoreceptors. To treat blindness, the mRNA will be engineered to create proteins able to edit vision-harming gene mutations.

“Our peptide is like a zip code, and the lipid nanoparticles are similar to an envelope that sends gene therapy in the mail. The peptide ensures mRNA is precisely delivered to photoreceptors—cells that we haven’t been able to target with lipid nanoparticles until now,” said Gaurav Sahay, PhD, associate professor at Oregon Science University College of Pharmacy and co-author of the study.

According to the researchers, the lipid nanoparticles are a promising alternative to AAV as they are flexible in size and able to deliver mRNA, which only keeps the gene-editing machinery active for a short time, preventing off-target edits. AAV particles can only carry DNA molecules, resulting in the continuous creation of gene-editing molecules.

For their study, the scientists used mice and nonhuman primates as model organisms to demonstrate lipid nanoparticle gene editing delivery to photoreceptors in the retina. Using green fluorescent protein to track the nanoparticles and various imaging techniques, the researchers were able to show that the mRNA bound to the nanoparticles successfully reached photoreceptors in the models.

“More than 250 genetic mutations have been linked to inherited retinal diseases, but only one has an approved gene therapy. 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,” concluded co-author Renee Ryals, PhD, assistant professor of ophthalmology at Oregon Health & Science University School of Medicine.

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