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[This article belongs to Volume - 70, Issue - 7]
Published on : 2025-07-21 14:56:28
Article Code: AMJ-21-07-2025-12324
Title : CRISPR-Cas9 Epigenetic Reprogramming of Microglia: A Novel Therapeutic Strategy for Alzheimer's Disease Modulation
Author(s) : Dr. Sarah Chen, Dr. James Al-Khatib, Dr. Maria Rodriguez
Abstract :
Alzheimer's disease (AD) pathogenesis is increasingly linked to microglial dysfunction and neuroinflammation. While
genetic editing approaches have shown promise, epigenetic modulation of microglial phenotype transitions remains
unexplored. This study introduces a novel CRISPR-dCas9-based epigenetic editing platform targeting the TREM2 and
CX3CR1 loci to induce M2-like anti-inflammatory microglial states in APP/PS1 transgenic mice. Using adeno
associated virus serotype 9 (AAV9) delivery vectors crossing the blood-brain barrier, we demonstrate sustained
transcriptional upregulation of phagocytic pathways and suppression of pro-inflammatory cytokine cascades. Our
findings reveal a 40% reduction in amyloid-beta plaque burden and significant restoration of synaptic density at 12
week post-intervention. Single-cell RNA sequencing confirmed stable epigenetic remodeling across microglial
subpopulations without off-target genomic integration. This work establishes epigenetic reprogramming as a viable
disease-modifying therapy for neurodegenerative disorders.