New gene delivery system to prevent vision loss: study

Scientists have developed nanoparticles that can deliver genes to target cells and prevent vision loss due to an inherited eye disorder - one of the most common causes of blindness in children.

Researchers from Case Western Reserve University in the US focused on the form of the disease called Leber congenital amaurosis 2 (LCA2).

Those with LAC2 carry a mutated RPE65 gene and suffer from profound vision loss from birth.

The mutated gene fails to produce RPE65 protein in the retinal pigment epithelium (RPE), a cell layer critical for protecting photoreceptors (rods and cones), researchers said.

The protein is an essential constituent of the visual cycle that converts light to electrical signals to the brain.

"We believe this technology can deliver almost any type of gene to tackle inherited visual disorders," said Zheng-Rong Lu, professor at Case Western Reserve.

Researchers designed a lipid-based nanoparticle called ECO to deliver healthy RPE65 genes to RPE cells.

The exterior of the nanoparticle is coated with nucleic acids that act as targeting agents, drawing the delivery system to the retina and facilitating uptake by RPE cells, researchers said.

To track activity, researchers included a fluorescent marker. Following injection into the retina of mice, the researchers could see fluorescent green concentrating in RPE cells.

Testing showed a significant increase in light-induced electrical activity from the eyes to the brain, indicating the rods and cones were operating as they should in the visual cycle.

The therapeutic effect lasted 120 days in treated mice. No improvements were observed in untreated mice, researchers said.

"The promise of this technology is it localises the drug to the photoreceptor cells, sparing the liver and kidney from exposure," said Krzysztof Palczewski from Case Western Reserve University.

"The nanoparticle uses a protein present in the eye to serve as an anchor, and the gene is delivered when bound," Palczewski said.

"While other researchers focus on using modified viruses to deliver genes for therapy, sometimes the genes are too large for viruses to carry. The ECO can be tailored to fit the cargo," said Lu.

Though researchers focused on LCA2, they believe the technology holds promise for other forms of LCA as well as other inherited diseases that lead to severe vision loss or blindness.

The study was published in the journal Molecular Therapy - Nucleic Acids.