Khan Mohamad Sultan, Qureshi Nousheen, Khan Rehan, Son Young-Ok, Maqbool Tariq
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.
Front Cell Neurosci. 2025 Apr 7;19:1578138. doi: 10.3389/fncel.2025.1578138. eCollection 2025.
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.
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。
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