Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2025 Apr 7:19:1578138.
doi: 10.3389/fncel.2025.1578138. eCollection 2025.

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

Affiliations
Review

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

Mohamad Sultan Khan et al. Front Cell Neurosci. .

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.

PubMed Disclaimer

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

FIGURE 1
FIGURE 1
Simplified structure of a typical CRISPR/Cas system.
FIGURE 2
FIGURE 2
Diagrammatic representation of the mechanism of action of CRISPR/Cas9.
FIGURE 3
FIGURE 3
Schematic representation of several important central nervous system-related disorders. AD: Alzheimer’s disease; PD: Parkinson’s disease; ALS: Amyotrophic lateral sclerosis; ASD: Autism spectrum disorder; ADHD: Attention-deficit/hyperactivity disorder; TBI: Traumatic brain injury.
FIGURE 4
FIGURE 4
Simplified mechanism involved in amyloid beta deposition and tau phosphorylation during the progression of Alzheimer’s disease (AD). During normal conditions, APP is processed involving α- and γ-secretase enzymes and the cytoskeleton of neurons, that is microtubules, are stabilized by Tau proteins leading to functional and healthy neurons and neuronal network. In AD condition, APP is processed by β- and γ-secretase enzymes leading to the formation of amyloid plaques between the synapses, blocking the neuronal network. Tau proteins are also hyperphosphorylated leading to destabilized microtubules contributing toward nonfunctional neuronal network. = Tau; = phosphorylation; = microtubules.
FIGURE 5
FIGURE 5
Basic and simplified diagram highlighting the application of CRISPR/Cas9 in developing Alzheimer’s disease (AD) model by carrying out various mutations and its therapeutic role. The figure also highlights the need for thoroughly investigating nanoparticles-based vectors (red) for CRISPR/Cas9.

Similar articles

Cited by

References

    1. Adli M. (2018). The CRISPR tool kit for genome editing and beyond. Nat. Commun. 9:1911. 10.1038/s41467-018-04252-2 - DOI - PMC - PubMed
    1. 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
    1. Ahmed M. E., Iyer S., Thangavel R., Kempuraj D., Selvakumar G. P., Raikwar S. P., et al. (2017). Co-localization of glia maturation factor with NLRP3 inflammasome and autophagosome markers in human Alzheimer’s disease brain. J. Alzheimers Dis. 60 1143–1160. 10.3233/JAD-170634 - DOI - PMC - PubMed
    1. Akhtar A., Singh S., Kaushik R., Awasthi R., Behl T. (2024). Types of memory, dementia, Alzheimer’s disease, and their various pathological cascades as targets for potential pharmacological drugs. Ageing Res. Rev. 96:102289. 10.1016/j.arr.2024.102289 - DOI - PubMed
    1. 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

LinkOut - more resources