In order for a potential gene therapy for a retinal degenerative disease to be effective, there needs to be a good way to deliver the therapy to the photoreceptors in the retina. One delivery strategy is to use lipid nanoparticles (also called LNPs), which are a protective shell that gets wrapped around the gene therapy cargo and helps the cargo enter its target cell.
One common challenge with using LNPs is that they tend to accumulate in certain cells in the body (like the liver) rather than in the retina. To overcome this challenge, Drs. Gaurav Sahay and Yulia Eygeris tested dozens of modifications in the lipids that make up the protective shell of the LNP. They tested how these modifications improved the ability of the LNPs to deliver cargo to the photoreceptors, and identified several candidates that were able to effectively deliver their cargo to rods and cones.
What this means for Usher syndrome: Gene therapy is a potential treatment for USH. However, one challenge for effective gene therapy is delivering the cargo (a health copy of a gene) to the right cells, like photoreceptors. It's also important to avoid delivering it to cells that don't need it. LNPs are a great candidate for gene therapy delivery because they can potentially carry very large cargo (like some of the USH genes). So, improvements in LNP technology that lead to effective delivery of large cargo to the photoreceptors can then be applied to USH subtypes that are caused by mutations in large genes.
