CRISPR/Cas9-Based therapeutics as a promising strategy for management of Alzheimer's disease: progress and prospects
- PMID: 40260080
- PMCID: PMC12009953
- DOI: 10.3389/fncel.2025.1578138
CRISPR/Cas9-Based therapeutics as a promising strategy for management of Alzheimer's disease: progress and prospects
Abstract
CRISPR/Cas9 technology has revolutionized genetic and biomedical research in recent years. It enables editing and modulation of gene function with an unparalleled precision and effectiveness. Among the various applications and prospects of this technology, the opportunities it offers in unraveling the molecular underpinnings of a myriad of central nervous system diseases, including neurodegenerative disorders, psychiatric conditions, and developmental abnormalities, are unprecedented. In this review, we highlight the applications of CRISPR/Cas9-based therapeutics as a promising strategy for management of Alzheimer's disease and transformative impact of this technology on AD research. Further, we emphasize the role of CRISPR/Cas9 in generating accurate AD models for identification of novel therapeutic targets, besides the role of CRISPR-based therapies aimed at correcting AD-associated mutations and modulating the neurodegenerative processes. Furthermore, various delivery systems are reviewed and potential of the non-viral nanotechnology-based carriers for overcoming the critical limitations of effective delivery systems for CRISPR/Cas9 is discussed. Overall, this review highlights the promise and prospects of CRISPR/Cas9 technology for unraveling the intricate molecular processes underlying the development of AD, discusses its limitations, ethical concerns and several challenges including efficient delivery across the BBB, ensuring specificity, avoiding off-target effects. This article can be helpful in better understanding the applications of CRISPR/Cas9 based therapeutic approaches and the way forward utilizing enormous potential of this technology in targeted, gene-specific treatments that could change the trajectory of this debilitating and incurable illness.
Keywords: Alzheimer’s disease; CNS; gene editing (CRISPR/Cas9); nanocarriers; therapeutics.
Copyright © 2025 Khan, Qureshi, Khan, Son and Maqbool.
Conflict of interest statement
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Figures





Similar articles
-
CRISPR/Cas9 gene editing: New hope for Alzheimer's disease therapeutics.J Adv Res. 2022 Sep;40:207-221. doi: 10.1016/j.jare.2021.07.001. Epub 2021 Jul 6. J Adv Res. 2022. PMID: 36100328 Free PMC article. Review.
-
CRISPR-Cas9 in Alzheimer's disease: Therapeutic trends, modalities, and challenges.Drug Discov Today. 2023 Aug;28(8):103652. doi: 10.1016/j.drudis.2023.103652. Epub 2023 Jun 7. Drug Discov Today. 2023. PMID: 37290639 Review.
-
CRISPR/Cas9 Delivery Potentials in Alzheimer's Disease Management: A Mini Review.Pharmaceutics. 2020 Aug 25;12(9):801. doi: 10.3390/pharmaceutics12090801. Pharmaceutics. 2020. PMID: 32854251 Free PMC article. Review.
-
Optimizing CRISPR/Cas9 precision: Mitigating off-target effects for safe integration with photodynamic and stem cell therapies in cancer treatment.Biomed Pharmacother. 2024 Nov;180:117516. doi: 10.1016/j.biopha.2024.117516. Epub 2024 Sep 26. Biomed Pharmacother. 2024. PMID: 39332185 Review.
-
Lipid nanoparticles: The game-changer in CRISPR-Cas9 genome editing.Heliyon. 2024 Jan 11;10(2):e24606. doi: 10.1016/j.heliyon.2024.e24606. eCollection 2024 Jan 30. Heliyon. 2024. PMID: 38288017 Free PMC article. Review.
Cited by
-
CRISPR/Cas9 and iPSC-Based Therapeutic Approaches in Alzheimer's Disease.Antioxidants (Basel). 2025 Jun 25;14(7):781. doi: 10.3390/antiox14070781. Antioxidants (Basel). 2025. PMID: 40722885 Free PMC article. Review.
References
-
- Aghamiri S., Talaei S., Ghavidel A. A., Zandsalimi F., Masoumi S., Hafshejani N. H., et al. (2020). Nanoparticles-mediated CRISPR/Cas9 delivery: Recent advances in cancer treatment. J. Drug Deliv. Sci. Technol. 56:101533. 10.1016/j.jddst.2020.101533 - DOI
-
- Akyuz E., Aslan F. S., Gokce E., Ilmaz O., Topcu F., Kakac S. (2024). Extracellular vesicle and CRISPR gene therapy: Current applications in Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and Huntington’s disease. Eur. J. Neurosci. 60 6057–6090. 10.1111/ejn.16541 - DOI - PubMed
Publication types
LinkOut - more resources
Full Text Sources