DMD, RIPK3, and MLKL gene editing by CRISPR Cas9 as myofiber protection against dystrophin deficiency and necroptosis in Duchenne muscular dystrophy: A literature review

Jordan Steven Widjaja; Arga Setyo Adji; Vira Aulia Kusuma Wardani; Eilien Levina Santoso; Fadhilla Rachmawati Sunarto; Fitri Handajani; Firman Suryadi Rahman

doi:10.53730/ijhs.v6nS6.10886

Authors

Jordan Steven Widjaja Medical Faculty of Hang Tuah University, Surabaya, Indonesia
Arga Setyo Adji Medical Faculty of Hang Tuah University, Surabaya, Indonesia
Vira Aulia Kusuma Wardani Medical Faculty of Hang Tuah University, Surabaya, Indonesia
Eilien Levina Santoso Medical Faculty of Hang Tuah University, Surabaya, Indonesia
Fadhilla Rachmawati Sunarto Medical Faculty of Hang Tuah University, Surabaya, Indonesia
Fitri Handajani
fitrihandajanidr@gmail.com
Biochemistry Laboratory Medical Faculty of Hang Tuah University, Surabaya, Indonesia
Firman Suryadi Rahman

Keywords:

duchenne muscular dystrophy, CRISPR-Cas9, DMD, RIPK3, MLKL

Abstract

BACKGROUND: Duchenne muscular dystrophy is a neuromuscular disease caused by a deficiency of dystrophin, which causes the skeletal and cardiac muscles to degenerate. Targeted deletion of DMD, RIPK3, and MLKL has been shown in several studies to prevent dystrophin deficiency and necroptosis, a critical hypothesis in the etiology of Duchenne muscular dystrophy. AIM: This research aimed to see if using CRISPR/Cas9 to target DMD, RIPK3, and MLKL is an effective therapeutic and if it has a long-term effect on Duchenne muscular dystrophy. METHODS: Abstracts and titles of articles were searched for specific keywords to summarize them using the method used in this study. The researcher will look over the entire article to see if it is valuable and relevant to the topic. RESULTS: CRISPR/Cas9-mediated genome editing in MDX mice can improve the primary genetic lesions that cause muscular dystrophy (DMD) and prevent disease development. Furthermore, Ripk3/Mlk1 double knockout completely blocked necroptosis susceptibility in necroptosis-sensitive cell lines, each to an indistinguishable degree. CONCLUSION: DMD, RIPK3, and MLKL gene editing by CRISPR/Cas9 is effective dystrophin insufficiency, sarcolemma fragility, poor intracellular signaling, myocyte death, inflammatory infiltration, muscle replacement, and necroptosis. However, more research is needed to determine its side effects and safety.

Downloads

Download data is not yet available.

References

Suryasa, I. W., Rodríguez-Gámez, M., & Koldoris, T. (2021). Health and treatment of diabetes mellitus. International Journal of Health Sciences, 5(1), i-v. https://doi.org/10.53730/ijhs.v5n1.2864

Suryasa, I. W., Rodríguez-Gámez, M., & Koldoris, T. (2021). The COVID-19 pandemic. International Journal of Health Sciences, 5(2), vi-ix. https://doi.org/10.53730/ijhs.v5n2.2937

Gustiani, R., Hakimi, M., & Suryaningsih, E. K. (2022). The implementation of referral system in postpartum hemorrhage cases by midwife. International Journal of Health & Medical Sciences, 5(3). https://doi.org/10.21744/ijhms.v5n3.1917

Aartsma-Rus, A., Van Deutekom, J. C. T., Fokkema, I. F., Van Ommen, G. J. B., & Den Dunnen, J. T. (2006). Entries in the Leiden Duchenne muscular dystrophy mutation database: An overview of mutation types and paradoxical cases that confirm the reading-frame rule. Muscle and Nerve, 34(2), 135–144. https://doi.org/10.1002/mus.20586

Alanis-Lobato, G., Zohren, J., McCarthy, A., Fogarty, N. M. E., Kubikova, N., Hardman, E., … Niakan, K. K. (2021). Frequent loss of heterozygosity in CRISPR-Cas9–edited early human embryos. Proceedings of the National Academy of Sciences, 118(22). https://doi.org/10.1073/pnas.2004832117

Amitai, G., & Sorek, R. (2016). CRISPR–Cas adaptation: insights into the mechanism of action. Nature Publishing Group, 1–10. https://doi.org/10.1038/nrmicro.2015.14

Amoasii, L., Hildyard, J. C. W., Li, H., Sanchez-Ortiz, E., Mireault, A., Caballero, D., … Olson, E. N. (2018). Gene editing restores dystrophin expression in a canine model of Duchenne muscular dystrophy. Science, 362(6410), 86–91. https://doi.org/10.1126/science.aau1549

Amoasii, L., Long, C., Li, H., Mireault, A. A., Shelton, J. M., Sanchez-Ortiz, E., … Olson, E. N. (2017). Single-cut genome editing restores dystrophin expression in a new mouse model of muscular dystrophy. Science Translational Medicine, 9(418). https://doi.org/10.1126/scitranslmed.aan8081

Bello, L., & Pegoraro, E. (2019). The “usual suspects”: Genes for inflammation, fibrosis, regeneration, and muscle strength modify duchenne muscular dystrophy. Journal of Clinical Medicine, 8(5), 1–23. https://doi.org/10.3390/jcm8050649

Bengtsson, N. E., Hall, J. K., Odom, G. L., Phelps, M. P., Andrus, C. R., Hawkins, R. D., … Chamberlain, J. S. (2017). Muscle-specific CRISPR/Cas9 dystrophin gene editing ameliorates pathophysiology in a mouse model for Duchenne muscular dystrophy. Nature Communications, 8, 1–9. https://doi.org/10.1038/ncomms14454

Birnkrant, D. J., Bushby, K., Bann, C. M., Apkon, S. D., Blackwell, A., Brumbaugh, D., … Weber, D. R. (2018, March). Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and neuromuscular, rehabilitation, endocrine, and gastrointestinal and nutritional management. The Lancet Neurology, Vol. 17, pp. 251–267. https://doi.org/10.1016/S1474-4422(18)30024-3

Chang, N. C., Chevalier, F. P., & Rudnicki, M. A. (2016). Satellite Cells in Muscular Dystrophy - Lost in Polarity. Trends in Molecular Medicine, 22(6), 479–496. https://doi.org/10.1016/j.molmed.2016.04.002

Chengzu Long, John R. McAnally, John M. Shelton, Alex A. Mireault, Rhonda Bassel- Duby, E. N. O. (2015). Prevention of muscular dystrophy in mice by CRISPR/Cas9–mediated editing of germline DNA. 345(6201), 1184–1188. https://doi.org/10.1126/science.1254445.Prevention

Cornelis, E., & Gessal, J. (2021). Duchene Muscular Disorder. Jurnal Medik Dan Rehabilitasi, 3(1), 1–10. Retrieved from https://ejournal.unsrat.ac.id/index.php/jmr/article/view/32925

David G Ousterout , Ami M Kabadi , Pratiksha I Thakore , William H Majoros , Timothy E Reddy, C. A. G. (2015). Multiplex CRISPR/Cas9-Based Genome Editing for Correction of Dystrophin Mutations that Cause Duchenne Muscular Dystrophy David. HHS Public Access. https://doi.org/10.1038/ncomms7244.Multiplex

De Los Angeles Beytía, M., Vry, J., & Kirschner, J. (2012). Drug treatment of Duchenne muscular dystrophy: Available evidence and perspectives. Acta Myologica, 31(MAY), 4–8.

Degterev, A., Huang, Z., Boyce, M., Li, Y., Jagtap, P., Mizushima, N., … Yuan, J. (2005). Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury. Nature Chemical Biology, 1(2), 112–119. https://doi.org/10.1038/nchembio711

Doetschman, T., & Georgieva, T. (2017). Gene Editing With CRISPR/Cas9 RNA-Directed Nuclease. 876–895. https://doi.org/10.1161/CIRCRESAHA.116.309727

Duchêne, B. L., Cherif, K., Iyombe-Engembe, J. P., Guyon, A., Rousseau, J., Ouellet, D. L., … Tremblay, J. P. (2018). CRISPR-Induced Deletion with SaCas9 Restores Dystrophin Expression in Dystrophic Models In Vitro and In Vivo. Molecular Therapy, 26(11), 2604–2616. https://doi.org/10.1016/j.ymthe.2018.08.010

Ehrke-Schulz, E., Schiwon, M., Leitner, T., Dávid, S., Bergmann, T., Liu, J., & Ehrhardt, A. (2017). CRISPR/Cas9 delivery with one single adenoviral vector devoid of all viral genes. Scientific Reports, 7(1), 1–11. https://doi.org/10.1038/s41598-017-17180-w

Erkut, E., & Yokota, T. (2022). CRISPR Therapeutics for Duchenne Muscular Dystrophy. International Journal of Molecular Sciences, 23(3), 1832. https://doi.org/10.3390/ijms23031832

Falzarano, M. S., Scotton, C., Passarelli, C., & Ferlini, A. (2015). Duchenne muscular dystrophy: From diagnosis to therapy. Molecules, 20(10), 18168–18184. https://doi.org/10.3390/molecules201018168

Fayssoil, A., Nardi, O., Orlikowski, D., & Annane, D. (2010). Cardiomyopathy in Duchenne muscular dystrophy: pathogenesis and therapeutics. Heart Failure Reviews, 15(1), 103–107. https://doi.org/10.1007/s10741-009-9156-8

Fletcher, S., Neri, M., Rossi, R., Trabanelli, C., Mauro, A., Selvatici, R., … Tessa, A. (2020). The Genetic Landscape of Dystrophin Mutations in Italy : A Nationwide Study. 11(March), 1–15. https://doi.org/10.3389/fgene.2020.00131

Fong, P., Turner, P. R., Denetclaw, W. F., & Steinhardt, R. A. (1990). Increased Activity of Calcium Leak Channels in Myotubes of Duchenne Human and mdx Mouse Origin. Science, 250(4981), 673–676. https://doi.org/10.1126/science.2173137

Gao, Q. Q., & McNally, E. M. (2015). The dystrophin complex: Structure, function, and implications for therapy. Comprehensive Physiology, 5(3), 1223–1239. https://doi.org/10.1002/cphy.c140048

Gupta, R., Sinharoy, S., Acharya, K., & Ghosh, D. (2019). CRISPR-Cas9 system: A new-fangled dawn in gene editing. Life Sciences, 116636. https://doi.org/10.1016/j.lfs.2019.116636

He, S., Wang, L., Miao, L., Wang, T., Du, F., Zhao, L., & Wang, X. (2009). Receptor Interacting Protein Kinase-3 Determines Cellular Necrotic Response to TNF-α. Cell, 137(6), 1100–1111. https://doi.org/10.1016/j.cell.2009.05.021

Hryhorowicz, M., Lipiński, D., Zeyland, J., & Słomski, R. (2017). CRISPR/Cas9 Immune System as a Tool for Genome Engineering. Archivum Immunologiae et Therapiae Experimentalis, 65(3), 233–240. https://doi.org/10.1007/s00005-016-0427-5

Hsu, P. D., Lander, E. S., & Zhang, F. (2014). Development and applications of CRISPR-Cas9 for genome engineering. Cell, 157(6), 1262–1278. https://doi.org/10.1016/j.cell.2014.05.010

Huang, J.-F., Shang, L., Zhang, M.-Q., Wang, H., Chen, D., Tong, J.-B., … Xiong, K. (2013). Differential neuronal expression of receptor interacting protein 3 in rat retina: involvement in ischemic stress response. BMC Neuroscience, 14(1), 16. https://doi.org/10.1186/1471-2202-14-16

Janik, E., Niemcewicz, M., Ceremuga, M., & Krzowski, L. (n.d.). Various Aspects of a Gene Editing System — CRISPR – Cas9.

Jiang, C., Meng, L., Yang, B., & Luo, X. (n.d.). Application of CRISPR/Cas9 gene editing technique in the study of cancer treatment. https://doi.org/10.1111/cge.13589

Jouan-Lanhouet, S., Riquet, F., Duprez, L., Vanden Berghe, T., Takahashi, N., & Vandenabeele, P. (2014). Necroptosis, in vivo detection in experimental disease models. Seminars in Cell & Developmental Biology, 35, 2–13. https://doi.org/10.1016/j.semcdb.2014.08.010

Khan, S., Mahmood, M. S., Rahman, S. U., Zafar, H., Habibullah, S., Khan, Z., & Ahmad, A. (2018). CRISPR/Cas9: The Jedi against the dark empire of diseases. Journal of Biomedical Science, 25(1), 1–18. https://doi.org/10.1186/s12929-018-0425-5

Koo, T., Lu-Nguyen, N. B., Malerba, A., Kim, E., Kim, D., Cappellari, O., … Kim, J. S. (2018). Functional Rescue of Dystrophin Deficiency in Mice Caused by Frameshift Mutations Using Campylobacter jejuni Cas9. Molecular Therapy, 26(6), 1529–1538. https://doi.org/10.1016/j.ymthe.2018.03.018

Kyrychenko, V., Kyrychenko, S., Tiburcy, M., Shelton, J. M., Long, C., Schneider, J. W., … Olson, E. N. (2017). Functional correction of dystrophin actin binding domain mutations by genome editing. JCI Insight, 2(18), 1–16. https://doi.org/10.1172/JCI.INSIGHT.95918

Lattanzi, A., Moiani, A., Izmiryan, A., Martin, S., Mavilio, F., Bovolenta, M., … Bernardi, F. (2017). Correction of the Exon 2 Duplication in DMD Myoblasts by a Single CRISPR/Cas9 System. Molecular Therapy - Nucleic Acids, 7(June), 11–19. https://doi.org/10.1016/j.omtn.2017.02.004

Lee, K., Conboy, M., Park, H. M., Jiang, F., Kim, H. J., Dewitt, M. A., … Murthy, N. (2017). Nanoparticle delivery of Cas9 ribonucleoprotein and donor DNA in vivo induces homology-directed DNA repair. Nature Biomedical Engineering, 1(11), 889–901. https://doi.org/10.1038/s41551-017-0137-2

Li, H. L., Fujimoto, N., Sasakawa, N., Shirai, S., Ohkame, T., Sakuma, T., … Hotta, A. (2015). Precise Correction of the Dystrophin Gene in Duchenne Muscular Dystrophy Patient Induced Pluripotent Stem Cells by TALEN and CRISPR-Cas9. Stem Cell Reports, 4(1), 143–154. https://doi.org/10.1016/j.stemcr.2014.10.013

Lim, K. R. Q., Yoon, C., & Yokota, T. (2018). Applications of CRISPR/Cas9 for the treatment of duchenne muscular dystrophy. Journal of Personalized Medicine, 8(4). https://doi.org/10.3390/jpm8040038

Lino, C. A., Harper, J. C., Carney, J. P., & Timlin, J. A. (2018). Delivering crispr: A review of the challenges and approaches. Drug Delivery, 25(1), 1234–1257. https://doi.org/10.1080/10717544.2018.1474964

Long, C., Amoasii, L., Mireault, A. A., & Mcanally, J. R. (2016). Postnatal genome editing partially restores dystrophin expression in a mouse model of muscular dystrophy. 351(6271), 400–403. https://doi.org/10.1126/science.aad5725.Postnatal

Long, C., Li, H., Tiburcy, M., Rodriguez-Caycedo, C., Kyrychenko, V., Zhou, H., … Olson, E. N. (2018). Correction of diverse muscular dystrophy mutations in human engineered heart muscle by single-site genome editing. Science Advances, 4(1), 1–11. https://doi.org/10.1126/sciadv.aap9004

Maggio, I., Liu, J., Janssen, J. M., Chen, X., & Gonçalves, M. A. F. V. (2016). Adenoviral vectors encoding CRISPR / Cas9 multiplexes rescue dystrophin synthesis in unselected populations of DMD muscle cells. Nature Publishing Group, (June), 1–12. https://doi.org/10.1038/srep37051

Maggio, I., Stefanucci, L., Janssen, J. M., Liu, J., Chen, X., Mouly, V., & Gonc, M. A. F. V. (2016). Selection-free gene repair after adenoviral vector transduction of designer nucleases : rescue of dystrophin synthesis in DMD muscle cell populations. 44(3), 1449–1470. https://doi.org/10.1093/nar/gkv1540

Mah, J. K. (2016). Current and emerging treatment strategies for Duchenne muscular dystrophy. Current Treatment Options in Neurology, 12, 1795–1807. https://doi.org/10.1007/s11940-018-0513-6

McCarter, G. C., & Steinhardt, R. A. (2000). Increased Activity of Calcium Leak Channels Caused by Proteolysis Near Sarcolemmal Ruptures. The Journal of Membrane Biology, 176(2), 169–174. https://doi.org/10.1007/s00232001086

Milanti Dewi, M., Putro Widodo, D., Amardiyanto, R., Sinaga, N., & Hidayah, N. (2018). Prevalensi, Spektrum Klinis dan Gambaran Neurofisiologi Kasus Neuromuskular. 20(4).

Min, Y.-L., Bassel-Duby, R., & Olson, E. N. (2019). CRISPR Correction of Duchenne Muscular Dystrophy. Annual Review of Medicine, 70(1), 239–255. https://doi.org/10.1146/annurev-med-081117-010451

Moat, S. J., Bradley, D. M., Salmon, R., Clarke, A., & Hartley, L. (2013). Newborn bloodspot screening for Duchenne Muscular Dystrophy: 21 years experience in Wales (UK). European Journal of Human Genetics, 21(10), 1049–1053. https://doi.org/10.1038/ejhg.2012.301

Moerke, C., Bleibaum, F., Kunzendorf, U., & Krautwald, S. (2019). Combined Knockout of RIPK3 and MLKL Reveals Unexpected Outcome in Tissue Injury and Inflammation. Frontiers in Cell and Developmental Biology, 7(February), 1–6. https://doi.org/10.3389/fcell.2019.00019

Morgan, J. E., Prola, A., Mariot, V., Pini, V., Meng, J., Hourde, C., … Bencze, M. (2018). Necroptosis mediates myofibre death in dystrophin-deficient mice. Nature Communications, 9(1). https://doi.org/10.1038/s41467-018-06057-9

Nelson, C. E., Hakim, C. H., Ousterout, D. G., Thakore, P. I., Moreb, E. A., Rivera, R. M. C., … Ann, F. (2017). In vivo genome editing improves muscle function in a mouse model of Duchenne muscular dystrophy. 351(6271), 403–407. https://doi.org/10.1126/science.aad5143.In

Ng, R., Metzger, J. M., Claflin, D. R., & Faulkner, J. A. (2008). Poloxamer 188 reduces the contraction-induced force decline in lumbrical muscles from mdx mice. American Journal of Physiology-Cell Physiology, 295(1), C146–C150. https://doi.org/10.1152/ajpcell.00017.2008

Ofengeim, D., Ito, Y., Najafov, A., Zhang, Y., Shan, B., DeWitt, J. P., … Yuan, J. (2015). Activation of Necroptosis in Multiple Sclerosis. Cell Reports, 10(11), 1836–1849. https://doi.org/10.1016/j.celrep.2015.02.051

Olson, E. N. (2021). Toward the correction of muscular dystrophy by gene editing. Proceedings of the National Academy of Sciences of the United States of America, 118(22). https://doi.org/10.1073/PNAS.2004840117

Ouellet, D. L., Barbeau, X., Rousseau, J., Chapdelaine, P., Lagüe, P., & Tremblay, J. P. (2016). Efficient Restoration of the Dystrophin Gene Reading Frame and Protein Structure in DMD Myoblasts Using the CinDel Method. (January), 1–12. https://doi.org/10.1038/mtna.2015.58

Paquin, R. S., Fischer, R., Mansfield, C., Mange, B., Beaverson, K., Ganot, A., … Peay, H. L. (2019). Priorities when deciding on participation in early-phase gene therapy trials for Duchenne muscular dystrophy: A best-worst scaling experiment in caregivers and adult patients. Orphanet Journal of Rare Diseases, 14(1), 1–9. https://doi.org/10.1186/s13023-019-1069-6

Porter, G. A., Dmytrenko, G. M., Winkelmann, J. C., & Bloch, R. J. (1992). Dystrophin colocalizes with β-spectrin in distinct subsarcolemmal domains in mammalian skeletal muscle. Journal of Cell Biology, 117(5), 997–1005. https://doi.org/10.1083/jcb.117.5.997

Romitti, P. A., Zhu, Y., Puzhankara, S., James, K. A., Nabukera, S. K., Zamba, G. K. D., … Bolen, J. (2015). Prevalence of Duchenne and Becker Muscular Dystrophies in the United. 135(3).

Ryder, S., Leadley, R. M., Armstrong, N., Westwood, M., De Kock, S., Butt, T., … Kleijnen, J. (2017). The burden, epidemiology, costs and treatment for Duchenne muscular dystrophy: An evidence review. Orphanet Journal of Rare Diseases, 12(1), 1–21. https://doi.org/10.1186/s13023-017-0631-3

Ryu, S. M., Koo, T., Kim, K., Lim, K., Baek, G., Kim, S. T., … Kim, J. S. (2018). Adenine base editing in mouse embryos and an adult mouse model of Duchenne muscular dystrophy. Nature Biotechnology, 36(6), 536–539. https://doi.org/10.1038/nbt.4148

Shastry, A., Aravind, S., Sunil, M., Ramesh, K., Ashley, B., Vedam, N. T., … Phalke, S. (2021). Matrilineal analysis of mutations in the DMD gene in a multigenerational South Indian cohort using DMD gene panel sequencing. (January), 1–12. https://doi.org/10.1002/mgg3.1633

Sinha, R., Sarkar, S., Khaitan, T., & Dutta, S. (2017). Duchenne muscular dystrophy: Case report and review. Journal of Family Medicine and Primary Care, 6(3), 654. https://doi.org/10.4103/2249-4863.222015

Sun, C., Serra, C., Lee, G., & Wagner, K. R. (2020). Stem cell-based therapies for Duchenne muscular dystrophy. Experimental Neurology, 323(Dmd), 1–28. https://doi.org/10.1016/j.expneurol.2019.113086

Tabebordbar, M., Zhu, K., Cheng, J. K. W., Chew, W. L., Widrick, J. J., Yan, W. X., … Amy, J. (2016). In vivo gene editing in dystrophic mouse muscle and muscle stem cells. 351(6271), 407–411. https://doi.org/10.1126/science.aad5177.In

Takeda, S., Clemens, P. R., & Hoffman, E. P. (2021). Exon-Skipping in Duchenne Muscular Dystrophy. Journal of Neuromuscular Diseases, 8(s2), S343–S358. https://doi.org/10.3233/JND-210682

Tomar, S., Moorthy, V., Sethi, R., Chai, J., Low, P. S., Hong, S. T. K., & Lai, P. S. (2019). Mutational spectrum of dystrophinopathies in Singapore: Insights for genetic diagnosis and precision therapy. American Journal of Medical Genetics, Part C: Seminars in Medical Genetics, 181(2), 230–244. https://doi.org/10.1002/ajmg.c.31704

Trichonas, G., Murakami, Y., Thanos, A., Morizane, Y., Kayama, M., Debouck, C. M., … Vavvas, D. G. (2010). Receptor interacting protein kinases mediate retinal detachment-induced photoreceptor necrosis and compensate for inhibition of apoptosis. Proceedings of the National Academy of Sciences, 107(50), 21695–21700. https://doi.org/10.1073/pnas.1009179107

Vijay Venugopal; Steven Pavlakis. (2021). Duchenne Muscular Dystrophy. StatPearls Publishing.

Vila, M. C., Rayavarapu, S., Hogarth, M. W., Van Der Meulen, J. H., Horn, A., Defour, A., … Jaiswal, J. K. (2017). Mitochondria mediate cell membrane repair and contribute to Duchenne muscular dystrophy. Cell Death and Differentiation, 24(2), 330–342. https://doi.org/10.1038/cdd.2016.127

Wang, H., Sun, L., Su, L., Rizo, J., Liu, L., Wang, L.-F., … Wang, X. (2014). Mixed Lineage Kinase Domain-like Protein MLKL Causes Necrotic Membrane Disruption upon Phosphorylation by RIP3. Molecular Cell, 54(1), 133–146. https://doi.org/10.1016/j.molcel.2014.03.003

Werneck, L. C., Lorenzoni, P. J., Ducci, R. D. P., Fustes, O. H., Kay, C. S. K., & Scola, R. H. (2019). Duchenne muscular dystrophy: An historical treatment review. Arquivos de Neuro-Psiquiatria, 77(8), 579–589. https://doi.org/10.1590/0004-282X20190088

Wojtal, D., Kemaladewi, D. U., Malam, Z., Abdullah, S., Wong, T. W. Y., Hyatt, E., … Ivakine, E. A. (2016). Spell Checking Nature : Versatility of CRISPR / Cas9 for Developing Treatments for Inherited Disorders. The American Journal of Human Genetics, 98(1), 90–101. https://doi.org/10.1016/j.ajhg.2015.11.012

Xu, L., Park, K. H., Zhao, L., Xu, J., Refaey, M. El, Gao, Y., … Han, R. (2016). CRISPR-mediated Genome Editing Restores Dystrophin Expression and Function in mdx Mice. 24(3), 564–569. https://doi.org/10.1038/mt.2015.192

Yao, S., Chen, Z., Yu, Y., Zhang, N., Jiang, H., Zhang, G., … Zhang, B. (2021). Current Pharmacological Strategies for Duchenne Muscular Dystrophy. Frontiers in Cell and Developmental Biology, Vol. 9. https://doi.org/10.3389/fcell.2021.689533

Yeung, E. W., Whitehead, N. P., Suchyna, T. M., Gottlieb, P. A., Sachs, F., & Allen, D. G. (2005). Effects of stretch-activated channel blockers on [Ca 2+ ] i and muscle damage in the mdx mouse. The Journal of Physiology, 562(2), 367–380. https://doi.org/10.1113/jphysiol.2004.075275

Young, C. S., Hicks, M. R., Ermolova, N. V., Nakano, H., Jan, M., Younesi, S., … Pyle, A. D. (2016). A Single CRISPR-Cas9 Deletion Strategy that Targets the Majority of DMD Patients Restores Dystrophin Function in hiPSC-Derived Muscle Cells. Cell Stem Cell, 18(4), 533–540. https://doi.org/10.1016/j.stem.2016.01.021

Young, C. S., Mokhonova, E., Quinonez, M., Pyle, A. D., & Spencer, M. J. (2017). Creation of a Novel Humanized Dystrophic Mouse Model of Duchenne Muscular Dystrophy and Application of a CRISPR/Cas9 Gene Editing Therapy. Journal of Neuromuscular Diseases, 4(2), 139–145. https://doi.org/10.3233/JND-170218

Yuan, J., Ma, Y., Huang, T., Chen, Y., Peng, Y., Li, B., … Chang, X. (2018). Genetic Modulation of RNA Splicing with a CRISPR-Guided Cytidine Deaminase. Molecular Cell, 72(2), 380-394.e7. https://doi.org/10.1016/j.molcel.2018.09.002

Zhang, T., Zhang, Y., Cui, M., Jin, L., Wang, Y., Lv, F., … Xiao, R.-P. (2016). CaMKII is a RIP3 substrate mediating ischemia- and oxidative stress–induced myocardial necroptosis. Nature Medicine, 22(2), 175–182. https://doi.org/10.1038/nm.4017

Zhang, Y., Long, C., Li, H., McAnally, J. R., Baskin, K. K., Shelton, J. M., … Olson, E. N. (2017). CRISPR-Cpf1 correction of muscular dystrophy mutations in human cardiomyocytes and mice. Science Advances, 3(4), 1–10. https://doi.org/10.1126/sciadv.1602814

Zhu, P., Wu, F., Mosenson, J., Zhang, H., He, T. C., & Wu, W. S. (2017). CRISPR/Cas9-Mediated Genome Editing Corrects Dystrophin Mutation in Skeletal Muscle Stem Cells in a Mouse Model of Muscle Dystrophy. Molecular Therapy - Nucleic Acids, 7(June), 31–41. https://doi.org/10.1016/j.omtn.2017.02.007