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基于CRISPR/Cas9的疗法作为治疗阿尔茨海默病的一种有前景的策略:进展与展望

CRISPR/Cas9-Based therapeutics as a promising strategy for management of Alzheimer's disease: progress and prospects.

作者信息

Khan Mohamad Sultan, Qureshi Nousheen, Khan Rehan, Son Young-Ok, Maqbool Tariq

机构信息

Laboratory of Nanotherapeutics and Regenerative Medicine, Department of Nanotechnology, University of Kashmir, Srinagar, India.

Department of Higher Education, Government of Jammu and Kashmir, Srinagar, India.

出版信息

Front Cell Neurosci. 2025 Apr 7;19:1578138. doi: 10.3389/fncel.2025.1578138. eCollection 2025.


DOI:10.3389/fncel.2025.1578138
PMID:40260080
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12009953/
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.

摘要

近年来,CRISPR/Cas9技术彻底改变了基因和生物医学研究。它能够以前所未有的精度和有效性编辑和调节基因功能。在这项技术的各种应用和前景中,它在揭示包括神经退行性疾病、精神疾病和发育异常在内的众多中枢神经系统疾病的分子基础方面提供的机会是前所未有的。在这篇综述中,我们强调基于CRISPR/Cas9的治疗方法作为治疗阿尔茨海默病的一种有前景的策略的应用,以及该技术对AD研究的变革性影响。此外,我们强调CRISPR/Cas9在生成准确的AD模型以识别新的治疗靶点方面的作用,以及基于CRISPR的疗法在纠正与AD相关的突变和调节神经退行性过程方面的作用。此外,还综述了各种递送系统,并讨论了基于非病毒纳米技术的载体在克服CRISPR/Cas9有效递送系统的关键局限性方面的潜力。总体而言,这篇综述强调了CRISPR/Cas9技术在揭示AD发展背后复杂分子过程方面的前景,讨论了其局限性、伦理问题以及包括跨血脑屏障有效递送、确保特异性、避免脱靶效应在内的几个挑战。本文有助于更好地理解基于CRISPR/Cas9的治疗方法的应用,以及利用该技术在靶向、基因特异性治疗中的巨大潜力的前进方向,这些治疗可能会改变这种使人衰弱且无法治愈疾病的进程。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f44/12009953/eec036528ccd/fncel-19-1578138-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f44/12009953/ce3331172420/fncel-19-1578138-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f44/12009953/482cd0181531/fncel-19-1578138-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f44/12009953/338453c6ca18/fncel-19-1578138-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f44/12009953/df5f50b0692d/fncel-19-1578138-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f44/12009953/eec036528ccd/fncel-19-1578138-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f44/12009953/ce3331172420/fncel-19-1578138-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f44/12009953/482cd0181531/fncel-19-1578138-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f44/12009953/338453c6ca18/fncel-19-1578138-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f44/12009953/df5f50b0692d/fncel-19-1578138-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f44/12009953/eec036528ccd/fncel-19-1578138-g005.jpg

相似文献

[1]
CRISPR/Cas9-Based therapeutics as a promising strategy for management of Alzheimer's disease: progress and prospects.

Front Cell Neurosci. 2025-4-7

[2]
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[3]
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[4]
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Pharmaceutics. 2020-8-25

[5]
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[6]
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[7]
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引用本文的文献

[1]
TIGR-Tas and the Expanding Universe of RNA-Guided Genome Editing Systems: A New Era Beyond CRISPR-Cas.

Genes (Basel). 2025-7-28

[2]
Combined Hyaluronic Acid Nanobioconjugates Impair CD44-Signaling for Effective Treatment Against Obesity: A Review of Comparison with Other Actors.

Int J Nanomedicine. 2025-8-21

[3]
CRISPR/Cas9 and iPSC-Based Therapeutic Approaches in Alzheimer's Disease.

Antioxidants (Basel). 2025-6-25

本文引用的文献

[1]
Applications of Gene Editing and Nanotechnology in Stem Cell-Based Therapies for Human Diseases.

Stem Cell Rev Rep. 2025-2-27

[2]
Safety issues of Donepezil combined with Memantine in Alzheimer's disease population: real-world pharmacovigilance.

Expert Opin Drug Saf. 2025-2-23

[3]
Comparative the efficacy and safety of Gosuranemab, Semorinemab, Tilavonemab, and Zagotenemab in patients with Alzheimer's disease: a systematic review and network meta-analysis of randomized controlled trials.

Front Aging Neurosci. 2025-1-29

[4]
Alzheimer's disease: assessing the therapeutic potential of anti-Aβ (Beta-Amyloid) treatments.

Cell Mol Biol (Noisy-le-grand). 2025-2-2

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The impact of rare genetic variants on Alzheimer disease.

Nat Rev Neurol. 2025-3

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Transl Neurodegener. 2025-1-27

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A de novo, mosaic and complex chromosome 21 rearrangement causes APP triplication and familial autosomal dominant early onset Alzheimer disease.

Sci Rep. 2025-1-23

[8]
Optimized prime editing of the Alzheimer's disease-associated APOE4 mutation.

Stem Cell Reports. 2025-1-14

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Ageing Res Rev. 2025-2

[10]
Animal models of Alzheimer's disease: Current strategies and new directions.

Zool Res. 2024-11-18

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