DNA nanoparticles were successfully used by researchers at the University of Oklahoma to express DNA in the rods and cones of mouse retinas, according to a new study. Researchers concluded that these nanoparticles appear to be a clinically viable, safe, and efficient alternative to using viral vectors for the expression of nucleic acids in the retina. This gene therapy technique has the potential for treating genetic-related vision problems, such as macular degeneration.

In the study, researchers injected several sites of the retina with DNA nanoparticles. One retina of each mouse was injected intravitreally with 1l of naked plasmid DNA.

After euthanizing the mice, each retina and each lens were individually harvested to measure the amounts of nanoparticle-driven DNA expression through fluorescence microscopy and electroretinography. Study results indicate that more than 95% of the retinal cells injected expressed the DNA nanoparticle, with no evidence of toxicity. Modification of the nanoparticle dose resulted in varying levels of genetic expression, which researchers suggest could be beneficial therapeutically.

Until now, viral vectors have been the most common method for genetic therapy. The virus is genetically altered so that, upon infection, it replicates not the viral cells, but the needed RNA strands, via a reverse transcriptase. But some viral vectors, such as those from lentiviruses, do not insert the genomes they carry onto a predictable section of the host DNA and can cause cancer through this uncontrolled replication. Others, such as retroviruses, integrate more stably, although there is still risk of cancerous growth.

This new study, however, suggests that DNA nanoparticle injection is a more feasiblenot to mention saferalternative.

Researchers hope to apply their findings to the development of DNA-based therapeutics for ocular disorders such as retinitis pigmentosa and macular degeneration. These exciting results suggest that genetic replacement therapy is feasible for various eye diseases, says Copernicus president and CEO Robert C. Moen, M.D., Ph.D., who assisted the study. The formulation permits a non-viral approach to treat human disease by introducing a normal copy of the underlying gene that is responsible for the disease process.

 

Farjo R, Skaggs J, Naash MI, et al. Efficient non-viral ocular gene transfer with compacted DNA nanoparticles. PLoS ONE 2006 Dec 20;1:e38.