Nanoparticles: unlocking genetic eye therapy?
Nanoparticle-delivered gene therapy successfully limited blinding retinal disease in rodents. Credit: Johns Hopkins Medicine

Nanoparticles: unlocking genetic eye therapy?

August 3, 2020 Staff reporters

An experimental trial has shown that nanoparticles can provide a safe and effective gene therapy vector for the treatment of wet age-related macular degeneration (AMD), potentially providing a future alternative to anti-VEGF injections.   

 

In the study, published by Science AdvancesJohns Hopkins University School of Medicine researchers used a specifically engineered large molecule, a nanoparticle, to enable them to compact large bundles of therapeutic DNA and deliver it into eye cells.  

 

Many gene therapy approaches depend on viral vectors, using a virus’ natural ability to carry genetic material into cellssaid study author, Professor Peter Campochiaro. Howevera viral vector creates an immune response, which prevents repeat dosing, and the most common one for ocular gene therapy cannot carry large genes, he said. “Some of the most prevalent inherited retinal degenerations are due to mutations in large genes that simply cannot fit into the most commonly used viral vector.  

 

To overcome these limitations, the Johns Hopkins team developed a new approach involving a biodegradable polymersurrounding and compacting long stretches of DNA, creating nanoparticles that can enter the cellsconverting eye cells into mini-factories for therapeutic protein. The study showed these nanoparticles effectively reached their target cells and deposited their genetic load in a rodent model 

 

The team also tested the nanoparticle’s ability to deliver a therapeutic gene for wet AMDThree weeks after injecting mice with nanoparticles containing the gene that neutralises the VEGF protein, they had a 60% reduction in abnormal blood vessels compared with the control mice. The same effect was seen 35 days later.  

 

“These results are extremely promising,” said co-author Dr Jordan Green, professor of biomedical engineering. “We have the ability to reach the cells most significantly affected by degenerative eye disease with non-viral treatments that can allow the eye to create its own sustained therapies.”