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 Advances, Johns 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 cells, said study author, Professor Peter Campochiaro. However, a 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 polymer, surrounding and compacting long stretches of DNA, creating nanoparticles that can enter the cells, converting 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 AMD. Three 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.
