Prime Editing in Neurogenetic Disorders: Molecular Mechanisms, Therapeutic Applications, and Translational Challenges
DOI:
https://doi.org/10.68041/medsc.v1i1/01Keywords:
CRISPR-Associated Protein 9, Gene Editing, Genetic Therapy, Heredodegenerative Disorders, Nervous System, Nervous System DiseasesAbstract
Genome editing has progressed rapidly, and prime editing is among the most impactful advances since the advent of CRISPR-Cas9. Rather than snipping both strands of DNA and repairing them, prime editors insert a new DNA sequence into the genome via a fused Cas9 nickase and reverse transcriptase, directed to the target sequence by an engineered pegRNA that encodes both the target address and the edit. That combination matters most in tissues where mistakes can't be undone, and few tissues fit that description better than the brain. This editorial briefly discusses the molecular basis of prime editing and then examines its current status for a selection of neurogenetic disorders: Tay-Sachs disease, Duchenne muscular dystrophy, Huntington disease, and Rett syndrome. Preclinical studies have demonstrated prime-editing applications in selected genetic disorders, while evidence for other conditions remains based on related genome-editing approaches, particularly base editing. The translational barriers that currently separate cell-based proof-of-concept from clinical application, including vector packaging constraints, blood-brain barrier penetration, and long-term safety in postmitotic neurons, are also discussed.
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