A light-responsive lipid nanoparticle platform delivering Cas9 RNP for VEGFA editing suppresses choroidal neovascularisation

Light-activated lipid nanoparticles delivering Cas9/sgRNA RNP achieve VEGFA disruption and, after a single intravitreal dose in a laser-induced rat CNV model, significantly suppress CNV.

• Why it matters: CNV causes irreversible vision loss, and repeated anti-VEGF injections create treatment burden and cumulative injection risk. Durable VEGFA editing is limited by safety concerns around uncontrolled VEGFA loss.
• What they did: The nanoparticles averaged ~130 nm hydrodynamic diameter (polydispersity 0.296) with 90.33% sgRNA encapsulation efficiency, releasing Cas9/sgRNA RNP under light. In human retinal pigment epithelial cells, illumination increased VEGFA disruption versus non-illuminated conditions, reducing VEGFA mRNA and protein.
• The result: In laser-induced rat CNV, light plus nanoparticles after a single intravitreal injection significantly reduced vascular leakage and CNV-associated structural abnormalities versus vehicle and non-illuminated controls, with no apparent nanoparticle-related retinal structural abnormalities.