CRISPR-Cas9 Gene Therapy for ALS Enhanced by TJ-Targeted Barrier Modulation

Amyotrophic Lateral Sclerosis (ALS) is the fatal motor neuron disease without effective treatment. AAV-mediated CRISPR/Cas9 editing represents a promising therapeutic strategy, but current data suggest that the blood-brain-barrier (BBB) limits the AAV entry into the brain, hindering its therapeutic efficacy. The goal of this application is to test the therapeutic efficacy of a novel strategy, which allows a significantly increased entry of AAV-CRIPR/Cas9 into the brain by plasmonic nanoparticles. We will be specifically responsible for assessing the therapeutic benefit of this treatment in the ALS mutant SOD1 mouse model.