Application prospect of CRISPR-Cas9 gene editing in epilepsy
DOI:
https://doi.org/10.54097/shcr4j47Keywords:
Epilepsy, CRISPR-Cas9 system, pathogenesis, gene therapy.Abstract
Epilepsy, a chronic noncommunicable brain disorder, is characterized by abnormal electrical activity in the brain, leading to seizures and disruptions in normal brain functions. Despite various known causes, a significant proportion of epilepsy cases remain unexplained. In recent years, Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR-Cas9) technology has emerged as a powerful tool for genetic engineering. Compared with the first two generations of gene-editing technology, it has the advantages of low cost, easy design and easy operation. Utilizing CRISPR activation (CRISPRa), researchers have explored the potential of increasing the expression of genes involved in regulating synaptic interactions to control epileptic activity. Studies on transgenic mice have shown that upregulating the Kv1.1 gene (Kcnal1), which encodes for a voltage-gated potassium channel responsible for regulating neuronal excitability, can reduce seizures and improve cognitive function. Additionally, CRISPR-Cas9 has been instrumental in creating animal models to study epilepsy, providing insights into gene functions, disease mechanisms, and potential therapeutic interventions. However, further research is needed to fully explore the potential of CRISPR-based therapies for targeted treatment of epilepsy. This review systematically introduces the pathogenesis of epilepsy, including the origins and causes of epilepsy and the mechanism of seizure formation and further discusses the application of the CRISPR/Cas9 system in epilepsy.
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References
Molecular mechanisms of epilepsy | Nature Neuroscience. (n.d.). Retrieved July 26, 2023, from https://www.nature.com/articles/nn.3947
Epilepsy. (n.d.). Retrieved July 26, 2023, from https://www.who.int/news-room/fact-sheets/detail/epilepsy
Wiechert, P., & Herbst, A. (1966). PROVOCATION OF CEREBRAL SEIZURES BY DERANGEMENT OF THE NATURAL BALANCE BETWEEN GLUTAMIC ACID AND γ-AMINOBUTYRIC ACID. Journal of Neurochemistry, 13(2), 59–64.
Banerjee, P. N., Filippi, D., & Allen Hauser, W. (2009). The descriptive epidemiology of epilepsy—A review. Epilepsy Research, 85(1), 31–45.
Wagnon, J. L. (2020). Promoting CRISPRa for Targeted Treatment of Epilepsy. Epilepsy Currents, 20(4), 227–229.
American Association of Neurological Surgeons. (2019). Epilepsy – Seizure Types, Symptoms and Treatment Options. American Association of Neurological Surgeons.
Bromfield, E. B., Cavazos, J. E., & Sirven, J. I. (2015). Basic Mechanisms Underlying Seizures and Epilepsy. American Epilepsy Society.
CDC. (2021, July 15). Bacterial Meningitis. Centers for Disease Control and Prevention.
Danoun MD, O. (2022, February 4). Focal Cortical Dysplasia. Epilepsy Foundation.
Izhikevich, E. M. (2006). Main page. Scholarpedia, 1(2), 1–1.
Kiriakopoulos MD, E. (2020, July 15). Traumatic Brain Injury and Epilepsy. Epilepsy Foundation.
Meningitis and Encephalitis Fact Sheet | National Institute of Neurological Disorders and Stroke. (2019). Nih.gov.
T;, U. F. C. (n.d.). CRISPR gene therapy: Applications, limitations, and implications for the future. Frontiers in oncology.
Stroik, S. (n.d.). CRISPR 101: Homology directed repair. Addgene blog.
Ran FA;Hsu PD;Wright J;Agarwala V;Scott DA;Zhang F; (n.d.). Genome engineering using the CRISPR-cas9 system. Nature protocols.
CF;, G. T. C. (n.d.). ZFN, Talen, and CRISPR/CAS-based methods for Genome Engineering. Trends in biotechnology.
Yeadon, J. (n.d.). Pros and cons of znfs, Talens, and CRISPR/Cas. The Jackson Laboratory.
CRISPR-Cas9, Talens and zfns - the battle in gene editing: Proteintech. Proteintech Group. (2023, July 12).
Raimondo JV, Heinemann U, de Curtis M, Goodkin HP, Dulla CG, Janigro D, Ikeda A, Lin CK, Jiruska P, Galanopoulou AS, Bernard C. Methodological standards for in vitro models of epilepsy and epileptic seizures. A TASK1-WG4 report of the AES/ILAE Translational Task Force of the ILAE. Epilepsia. 2017 Nov;58 Suppl 4(Suppl 4):40-52.
Qin W, Kutny PM, Maser RS, Dion SL, Lamont JD, Zhang Y, Perry GA, Wang H. Generating Mouse Models Using CRISPR-Cas9-Mediated Genome Editing. Curr Protoc Mouse Biol. 2016 Mar 1;6(1):39-66.
Rubio C, Rubio-Osornio M, Retana-Márquez S, Verónica Custodio ML, Paz C. In vivo experimental models of epilepsy. Cent Nerv Syst Agents Med Chem. 2010 Dec 1;10(4):298-309.
Javaid, M.S.; Tan, T.; Dvir, N.; Anderson, A.; J. O’Brien, T.; Kwan, P.; Antonic-Baker, A. Human In Vitro Models of Epilepsy Using Embryonic and Induced Pluripotent Stem Cells. Cells 2022, 11, 3957.
Dulla, C.G., Janigro, D., Jiruska, P., Raimondo, J.V., Ikeda, A., Lin, C.-C.K., Goodkin, H.P., Galanopoulou, A.S., Bernard, C. and de Curtis, M. (2018), How do we use in vitro models to understand epileptiform and ictal activity? A report of the TASK1-WG4 group of the ILAE/AES Joint Translational Task Force. Epilepsia Open, 3: 460-473.
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