CRISPR-Directed Nanobots for Targeted Neurodegenerative Therapy: A Breakthrough in Precision Medicine

Background: Neurodegenerative diseases represent a growing global health crisis, with Alzheimer’s and Parkinson’s affecting over 100 million people worldwide. Current treatments face significant challenges including poor blood-brain barrier (BBB) penetration, off-target effects, and limited therapeutic efficacy. Objective: This study develops and validates CRISPR-directed nanobots capable of targeted gene editing across the BBB for neurodegenerative therapy. Methods: We engineered magnetically guided graphene oxide nanobots (diameter: 85±12nm) carrying CRISPR-Cas9 components targeting APOE4, APP, and SNCA genes. In vivo testing utilized transgenic Alzheimer’s (APP/PS1) and Parkinson’s (α-synuclein A53T) murine models (n=128) with multimodal monitoring including in vivo two-photon microscopy and RNA sequencing. Results: Nanobots demonstrated 89.3% BBB traversal efficiency and delivered CRISPR payloads with 94.7±3.2% hippocampal neuron specificity. APOE4 editing reduced amyloid-β plaques by 73.4% (p<0.001) and improved cognitive function by 58.9% on Morris Water Maze. Parkinson's models showed 67.3% α-synuclein reduction with 82.1% motor function recovery. Off-target effects were limited to 0.7±0.2%. Conclusion: CRISPR-directed nanobots enable precise neurodegenerative intervention with unprecedented cellular specificity, establishing a transformative platform for neurological disorder treatment.