DNA nanoparticles successful in treating RP in mice

DNA compacted nanotechnology, a non-viral technology, has been used to rescue a murine model with retinitis pigmentosa with haploid insufficiency (referred to as retinal degeneration slow [RDS], said Muna Naash, PhD, of the Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City.

In their study, investigators combined the nanoparticles with DNA and injected the nanoparticles subretinally. They used 8- to 11-nanometer acetate particles to test the level of expression in the retinas of adult mice.

Dr. Naash and her colleagues found "enormous expression" in the retina and pigment epithelium in this animal model. Testing of the functional recovery after the subretinal injection indicated that 1 month later the electroretinography results for the rods and cones recovered, indicating that the nanoparticles are nontoxic. Importantly, expression was present up to 120 days post-injection. In newborn animals, there also was full recovery of the rods and cones.

This RDS model has about a 70% reduction in the rod a-wave and about a 40% reduction in the cone b-wave in animals aged 7 months. Dr. Naash reported that functional improvement was seen in the rod a-wave and a four-fold increase in the scotopic a-wave. The improvement was found to decrease over time. In adult animals, investigators also saw high expression levels (three-fold compared with uninjected eyes) with expression seen in almost all photoreceptor cells and functional improvements in the scotopic a-waves and photopic b-waves.

"Compacted DNA nanoparticles are effective in a nonviral delivery method," Dr. Naash said. "They are highly effective in transfected dividing and nondividing cells. The nanoparticles can target multiple ocular cell types and mediate high levels of gene expression up to 120 days after injection.

"Finally, this technology can rescue functionally and structurally the phenotype in the RDS model," she concluded.