Researchers take crucial step towards new treatment for genetic blindness

Lipid nanoparticles & mRNA show promise for treating hereditary blindness.
Mert Erdemir
Nanoparticles entering neural retina.
Nanoparticles entering neural retina.

Gaurav Sahay, OSU College of Pharmacy 

Scientists from the Oregon State University College of Pharmacy have shown in animal studies that it may be possible to treat a rare genetic condition that causes blindness using lipid nanoparticles and messenger RNA, which are the same technologies used in COVID-19 vaccines.

The researchers developed nanoparticles that are able to enter the neural retina and deliver mRNA to the photoreceptor cells, which are responsible for sensing light and converting it into neural signals that are sent to the brain.

Overcoming the main limitation of using lipid nanoparticles

The researchers were able to successfully handle the challenge of using lipid nanoparticles (LNPs) to deliver genetic material for vision therapy, ensuring that the particles reached the retina at the back of the eye.

Lipids are a diverse group of biomolecules that includes molecules like fatty acids and oils, as well as natural oils and waxes. Nanoparticles are extremely small pieces of material, with sizes ranging from one to one hundred billionths of a meter. Messenger RNA are genetic molecules that give cells the instructions they need to create a specific protein.

In the case of inherited retinal degeneration (IRD), the mRNA delivered by LNPs instructs the defective photoreceptor cells caused by a genetic mutation to produce the necessary proteins for vision.

Studies on mice and non-human primates demonstrated that LNPs fitted with peptides were able to get past obstacles in the eye and reach the neural retina, where light is converted into electric signals that the brain then converts into images.

"We identified a novel set of peptides that can reach the back of the eye. We used these peptides to act as zip codes to deliver nanoparticles carrying genetic materials to the intended address within the eye," Gaurav Sahay, OSU associate professor of pharmaceutical sciences, said in a press release.

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"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.

The study attempts to develop solutions to the difficulties associated with the current principal method of gene editing delivery: Adeno-associated virus (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 study was published today in Science Advances.