ArticleStem cell reports2025
Optimized prime editing of the Alzheimer's disease-associated APOE4 mutation.
Article in Stem cell reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- Therapeutic Gene Editing of APOE4 in Sporadic Alzheimer's Disease via Prime Editor 7.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Protective mutations associated with APOE in Alzheimer's disease.Molecular psychiatry · 2026Review
- Targeting Mitochondria in Aging-Related Diseases: Therapeutic Potential and Obstacles.MedComm · 2026Review
- Gene-sized editing for the therapy of genetic diseases.Functional & integrative genomics · 2026Review
- Executive Summary of 2025 International Conference of the Korean Dementia Association and International Congress of the Asian Society Against Dementia (IC-KDA/ASAD 2025): A Report From the Academic Committee of the Korean Dementia Association.Dementia and neurocognitive disorders · 2025Review
- Clinical Significance of APOE4 Genotyping: Potential for Personalized Therapy and Early Diagnosis of Alzheimer's Disease.Journal of clinical medicine · 2025Review
- In Vitro Correction of Point Mutations in theInternational journal of molecular sciences · 2025Article
- CRISPR-Cas technologies in neurodegenerative disorders: mechanistic insights, therapeutic potential, and translational challenges.Frontiers in neurology · 2025Review
- CRISPR/Cas9-Based therapeutics as a promising strategy for management of Alzheimer's disease: progress and prospects.Frontiers in cellular neuroscience · 2025Review
- Trained immunity in atherosclerosis: plasticity, metabolic-vascular axis, and AI-driven precision remodeling.Frontiers in immunology · 2025Review
- Spatial distribution characteristics and influencing factors of China martial arts schools based on Baidu map API.PloS one · 2025Article
Corrections and comments
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Gene editing strategies to safely and robustly modify the Alzheimer's disease-associated APOE4 isoform are still lacking. Prime editing (PE) enables the precise introduction of genetic variants with minimal unintended editing and without donor templates. However, it requires optimization for each target site and has not yet been applied to APOE4 gene editing. Here, we screened PE guide RNA (pegRNA) parameters and PE systems for introducing the APOE4 variant and applied the optimized PE strategy to generate disease-relevant human induced pluripotent stem cell models. We show that introducing a single-nucleotide difference required for APOE4 correction inhibits PE activity. To advance efficient and robust genome engineering of precise genetic variants, we further present a reliable PE enrichment strategy based on diphtheria toxin co-selection. Our work provides an optimized and reproducible genome engineering pipeline to generate APOE4 disease models and outlines novel strategies to accelerate genome editing in cellular disease model generation.
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