Brain-Targeted Nano delivery System for CRISPRa-Mediated Activation of the Arc Gene in Alzheimer’s Disease

Yibing Lu

doi:10.54097/7axcw386

Authors

Yibing Lu

DOI:

https://doi.org/10.54097/7axcw386

Keywords:

Alzheimer’s disease, CRISPR activation (CRISPRa), Arc gene, Nanodelivery, Brain-targeted gene therapy.

Abstract

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by cognitive decline and synaptic dysfunction, for which effective treatments remain lacking. Recent advances in CRISPR activation (CRISPRa) systems and nanodelivery platforms have opened new therapeutic avenues, particularly through modulation of Arc gene expression to improve synaptic plasticity. However, efficient brain-targeted delivery remains a critical challenge. This study systematically analyzes the molecular mechanisms of CRISPRa-mediated Arc gene regulation and its therapeutic potential in AD, with a focus on optimizing delivery strategies such as lipid nanoparticles (LNPs) with ligand modifications and improved immunocompatibility to enhance brain-targeting efficiency. Current evidence demonstrates considerable promise in vitro and in animal models, though the precise activation of Arc by CRISPRa requires further validation. The findings provide valuable insights for AD gene therapy and nanodelivery technologies, while emphasizing the need for further optimization of delivery system safety and scalability. Future work should focus on multi-ligand synergistic targeting, immune modulation, and standardized manufacturing processes to facilitate clinical translation.

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