Download pdf
CRISPR/Cas9 gene editing: A promising approach towards Huntington’s Disease
- 1 University High School
* Author to whom correspondence should be addressed.
Abstract
Huntington's Disease (HD) is an incurable neurodegenerative condition marked by the gradual decline of motor abilities, cognitive capabilities, and emotional stability. It results from a mutation in the Huntingtin gene (HTT), which triggers the generation of a harmful variant of the Huntingtin protein known as mutant Huntingtin (mHTT). Despite significant advancements in understanding the disease's molecular basis, effective treatments to halt or reverse its progression remain elusive. Over the past few years, the groundbreaking genetic modification technique called Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) has risen as a hopeful tool in the realm of genetic investigation and treatment. CRISPR has the potential to precisely target and modify specific genes, offering new possibilities for the treatment of Huntington's Disease. This paper aims to provide an overview of Huntington's Disease, the CRISPR technology, and its potential applications in addressing the underlying genetic causes of HD. By exploring the fundamental aspects of both HD and CRISPR, this paper hopes to provide a clearer picture to the therapeutic potential of CRISPR in mitigating the effects of this neurodegenerative disorder.
Keywords
CRISPR Cas9, Huntington’s Disease, gene editing, neurodegenerative disorder
[1]. Walker, F. O. (2007). Huntington’s disease. The Lancet, 369(9557), 218–228. https://doi.org/10. 1016/s0140-6736(07)60111-1
[2]. Roos, R. A. (2010). Huntington’s disease: a clinical review. Orphanet Journal of Rare Diseases, 5(1). https://doi.org/10.1186/1750-1172-5-40
[3]. Adli, M. (2018). The CRISPR tool kit for genome editing and beyond. Nature Communications, 9(1). https://doi.org/10.1038/s41467-018-04252-2
[4]. Baumann, M. (2016). CRISPR/Cas9 genome editing – new and old ethical issues arising from a revolutionary technology. NanoEthics, 10(2), 139–159. https://doi.org/10.1007/s11569-016-0259-0
[5]. Gostimskaya, I. (2022). CRISPR–Cas9: A History of Its Discovery and Ethical Considerations of Its Use in Genome Editing. Biochemistry (Moscow), 87(8), 777–788. https://doi.org/10. 1134/ s0006297922080090
[6]. Gupta, D., Bhattacharjee, O., Mandal, D., Sen, M. K., Dey, D., Dasgupta, A., Kazi, T. A., Gupta, R., Sinharoy, S., Acharya, K., Chattopadhyay, D., Ravichandiran, V., Roy, S., & Ghosh, D. (2019). CRISPR-Cas9 system: A new-fangled dawn in gene editing. Life Sciences, 232, 116636. https://doi.org/10.1016/j.lfs.2019.116636
[7]. Vachey, G., & Déglon, N. (2018). CRISPR/Cas9-Mediated Genome Editing for Huntington’s Disease. Methods in Molecular Biology (Clifton, N.J.), 1780, 463–481. https://doi.org/10. 1007/978-1-4939-7825-0_21
[8]. Boudreau, R. L., McBride, J. L., Martins, I., Shen, S., Xing, Y., Carter, B. J., & Davidson, B. L. (2009). Nonallele-specific Silencing of Mutant and Wild-type Huntingtin Demonstrates Therapeutic Efficacy in Huntington’s Disease Mice. Molecular Therapy: The Journal of the American Society of Gene Therapy, 17(6), 1053–1063. https://doi.org/10.1038/mt.2009.17
[9]. Drouet, V., Ruiz, M., Zala, D., Feyeux, M., Auregan, G., Cambon, K., Troquier, L., Carpentier, J., Aubert, S., Merienne, N., Bourgois-Rocha, F., Hassig, R., Rey, M., Dufour, N., Saudou, F., Perrier, A. L., Hantraye, P., & Déglon, N. (2014). Allele-Specific Silencing of Mutant Huntingtin in Rodent Brain and Human Stem Cells. PLoS ONE, 9(6), e99341. https://doi.org/10.1371/journal.pone.0099341
[10]. Lee, J.M., Gillis, T., Mysore, J. S., Ramos, E. M., Myers, R. H., Hayden, M. R., Morrison, P. J., Nance, M., Ross, C. A., Margolis, R. L., Squitieri, F., Griguoli, A., Di Donato, S., Gomez-Tortosa, E., Ayuso, C., Suchowersky, O., Trent, R. J., McCusker, E., Novelletto, A., & Frontali, M. (2012). Common SNP-based haplotype analysis of the 4p16.3 Huntington disease gene region. American Journal of Human Genetics, 90(3), 434–444. https://doi.org/10.1016/ j.ajhg.2012.01.005
[11]. Bolukbasi, M. F., Gupta, A., Oikemus, S., Derr, A. G., Garber, M., Brodsky, M. H., Zhu, L. J., & Wolfe, S. A. (2015). DNA-binding-domain fusions enhance the targeting range and precision of Cas9. Nature Methods, 12(12), 1150–1156. https://doi.org/10.1038/nmeth.3624
[12]. Doench, J. G., Fusi, N., Sullender, M., Hegde, M., Vaimberg, E. W., Donovan, K. F., Smith, I., Tothova, Z., Wilen, C., Orchard, R., Virgin, H. W., Listgarten, J., & Root, D. E. (2016). Optimized sgRNA design to maximize activity and minimize off-target effects of CRISPR-Cas9. Nature Biotechnology, 34(2), 184–191. https://doi.org/10.1038/nbt.3437
[13]. Tycko, J., Myer, Vic E., & Hsu, Patrick D. (2016). Methods for Optimizing CRISPR-Cas9 Genome Editing Specificity. Molecular Cell, 63(3), 355–370. https://doi.org/10.1016/j. molcel.2016.07.004
[14]. Doench, J. G., Hartenian, E., Graham, D. B., Tothova, Z., Hegde, M., Smith, I., Sullender, M., Ebert, B. L., Xavier, R. J., & Root, D. E. (2014). Rational design of highly active sgRNAs for CRISPR-Cas9–mediated gene inactivation. Nature Biotechnology, 32(12), 1262–1267. https://doi.org/10.1038/nbt.3026
[15]. Fu, Y., Sander, J. D., Reyon, D., Cascio, V. M., & Joung, J. K. (2014). Improving CRISPR-Cas nuclease specificity using truncated guide RNAs. Nature Biotechnology, 32(3), 279–284. https://doi.org/10.1038/nbt.2808
[16]. Mali, P., Yang, L., Esvelt, K. M., Aach, J., Guell, M., DiCarlo, J. E., Norville, J. E., & Church, G. M. (2013). RNA-Guided Human Genome Engineering via Cas9. Science, 339(6121), 823–826. https://doi.org/10.1126/science.1232033
[17]. Monteys, A. M., Ebanks, S. A., Keiser, M. S., & Davidson, B. L. (2017). CRISPR/Cas9 Editing of the Mutant Huntingtin Allele In Vitro and In Vivo. Molecular Therapy, 25(1), 12–23. https://doi.org/10.1016/j.ymthe.2016.11.010
[18]. Kabadi, A. M., Ousterout, D. G., Hilton, I. B., & Gersbach, C. A. (2014). Multiplex CRISPR/Cas9-based genome engineering from a single lentiviral vector. Nucleic Acids Research, 42(19), e147–e147. https://doi.org/10.1093/nar/gku749
[19]. Liu, J., & Shui, S. (2016). Delivery methods for site-specific nucleases: Achieving the full potential of therapeutic gene editing. Journal of Controlled Release, 244, 83–97. https://doi.org/10.1016/j.jconrel.2016.11.014
[20]. Wang, L., Li, F., Dang, L., Liang, C., Wang, C., He, B., Liu, J., Li, D., Wu, X., Xu, X., Lu, A., & Zhang, G. (2016). In Vivo Delivery Systems for Therapeutic Genome Editing. International Journal of Molecular Sciences, 17(5), 626. https://doi.org/10.3390/ijms17050626
[21]. Ran, F. A. (2017). Adaptation of CRISPR nucleases for eukaryotic applications. Analytical Biochemistry, 532, 90–94. https://doi.org/10.1016/j.ab.2016.10.018
[22]. Yang, S., Chang, R., Yang, H., Zhao, T., Hong, Y., Kong, H. E., Sun, X., Qin, Z., Jin, P., Li, S., & Li, X.-J. (2017). CRISPR/Cas9-mediated gene editing ameliorates neurotoxicity in mouse model of Huntington’s disease. Journal of Clinical Investigation, 127(7), 2719–2724. https://doi.org/10.1172/jci92087
[23]. Smith, C., Gore, A., Yan, W., Abalde-Atristain, L., Li, Z., He, C., Wang, Y., Brodsky, Robert A., Zhang, K., Cheng, L., & Ye, Z. (2014). Whole-Genome Sequencing Analysis Reveals High
[24]. Slaymaker, I. M., Gao, L., Zetsche, B., Scott, D. A., Yan, W. X., & Zhang, F. (2015). Rationally engineered Cas9 nucleases with improved specificity. Science, 351(6268), 84–88. https://doi.org/10.1126/science.aad5227
[25]. Tsai, S. Q., Zheng, Z., Nguyen, N. T., Liebers, M., Topkar, V. V., Thapar, V., Wyvekens, N., Khayter, C., Iafrate, A. J., Le, L. P., Aryee, M. J., & Joung, J. K. (2014). GUIDE-seq enables genome-wide profiling of off-target cleavage by CRISPR-Cas nucleases. Nature Biotechnology, 33(2), 187–197. https://doi.org/10.1038/nbt.3117
Cite this article
Liu,I.I. (2023). CRISPR/Cas9 gene editing: A promising approach towards Huntington’s Disease. Theoretical and Natural Science,24,19-24.
Data availability
The datasets used and/or analyzed during the current study will be available from the authors upon reasonable request.
Disclaimer/Publisher's Note
The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of EWA Publishing and/or the editor(s). EWA Publishing and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.
About volume
Volume title: Proceedings of the 3rd International Conference on Biological Engineering and Medical Science
© 2024 by the author(s). Licensee EWA Publishing, Oxford, UK. This article is an open access article distributed under the terms and
conditions of the Creative Commons Attribution (CC BY) license. Authors who
publish this series agree to the following terms:
1. Authors retain copyright and grant the series right of first publication with the work simultaneously licensed under a Creative Commons
Attribution License that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this
series.
2. Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the series's published
version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial
publication in this series.
3. Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and
during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See
Open access policy for details).