Nanotechnology Advancements Show Promise for Gene Therapy Treatments for Blindness

According to research published in OSHU, nanotechnology has allowed a revolutionary gene therapy method in the form of mRNA-based COVID-19 vaccines that may one day help physicians treat hereditary types of blindness.  

A team of Oregon State University and Oregon Health & Science University researchers discovered a mechanism to transport messenger ribonucleic acid (mRNA) into the retina using lipid nanoparticles or little lab-made fat balls. To restore eyesight, scientists must use mRNA to produce proteins that can repair the defective genes that cause blindness. 

The team reveals how they use a lipid nanoparticle delivery technique to target photoreceptors in the eyes of mice and nonhuman primates in a paper published today in Science Advances. Researchers noticed that coating the system’s nanoparticles with a peptide made them more appealing to the body’s photoreceptors, so they made this alteration.  

According to Dr. Gaurav Sahay, corresponding author, and associate professor at the OSU College of Pharmacy with a dual research position at the OHSU Casey Eye Institute, “our peptide is like a zip code,” and the lipid nanoparticles are like an envelope that distributes gene therapy through the mail.   

“Over 250 genetic variations have been linked to hereditary retinal illnesses,” said Renee Ryals, Ph.D., associate professor of ophthalmology at OHSU and scientist at the OHSU Casey Eye Institute. If gene therapy technology advances, it may offer new therapeutic options for blindness prevention.   

In 2017, the FDA authorized the first gene therapy to treat a hereditary form of blindness. Many patients have benefitted from the medicine known as Luxturna, which has helped them keep or regain their vision. The genetic engineering components are carried via a modified adeno-associated virus (AAV) variant.  

Although AAV is commonly employed in modern gene treatments, it has problems. Due to its small size, the virus is physically incapable of containing the complicated gene-editing machinery required to make some types of alterations. Additionally, because AAV-based gene therapy can only transport DNA, it necessitates the continual development of gene-editing agents, which may result in unwanted genetic modifications.  

Because their size is not a limiting issue, lipid nanoparticles might be used in place of AAV. Lipidomic nanoparticles also transport messenger RNA, which can keep gene-editing tools active for a limited period, reducing the potential of undesirable off-target editing.

The success of mRNA-based COVID-19 vaccines, which also employ lipid nanoparticles to deliver mRNA, further validated the promise of lipid nanoparticles. These vaccines were the first to be approved against COVID-19 in the United States, thanks to their rapid and significant production.  

Sahay, Ryals, and colleagues proved that lipid nanoparticles coated with peptides might be guided to the retina, the portion of the eye responsible for vision. They encapsulated mRNA for green fluorescent protein in nanoparticles to illustrate the practicality of this method.   After giving this nanoparticle-based gene therapy model intravitreally to mice and nonhuman primates, researchers examined the treated animals’ eyes using several imaging techniques.

The animals’ retinas fluoresce green, suggesting that the outer lipid bilayer of the lipid nanoparticles could reach photoreceptors and that the mRNA provided by the lipid bilayer could penetrate the retina and create green fluorescent protein. Before, no one knew if lipid nanoparticles could enter the nonhuman primate eye and reach the photoreceptors.  

The expression of green fluorescent protein in animal retina models is still being studied. They are also seeking to improve a treatment that employs messenger RNA (mRNA), which has the potential to change genes.