Wu Junhao, Tao Yong, Deng Di, Meng Zhaoli, Zhao Yu
Department of Otorhinolaryngology-Head & Neck Surgery, West China Hospital of Sichuan University, Chengdu, 610041, China.
Department of Audiology and Speech Language Pathology, West China Hospital of Sichuan University, Chengdu, China.
Cell Biosci. 2023 May 20;13(1):93. doi: 10.1186/s13578-023-01021-7.
Hearing loss (HL) can be caused by a number of different genetic factors. Non-syndromic HL refers that HL occurs as an isolated symptom in an individual, whereas syndromic HL refers that HL is associated with other symptoms or abnormalities. To date, more than 140 genes have been identified as being associated with non-syndromic HL, and approximately 400 genetic syndromes can include HL as one of the clinical symptoms. However, no gene therapeutic approaches are currently available to restore or improve hearing. Therefore, there is an urgent necessity to elucidate the possible pathogenesis of specific mutations in HL-associated genes and to investigate the promising therapeutic strategies for genetic HL. The development of the CRISPR/Cas system has revolutionized the field of genome engineering, which has become an efficacious and cost-effective tool to foster genetic HL research. Moreover, several in vivo studies have demonstrated the therapeutic efficacy of the CRISPR/Cas-mediated treatments for specific genetic HL. In this review, we briefly introduce the progress in CRISPR/Cas technique as well as the understanding of genetic HL, and then we detail the recent achievements of CRISPR/Cas technique in disease modeling and therapeutic strategies for genetic HL. Furthermore, we discuss the challenges for the application of CRISPR/Cas technique in future clinical treatments.
听力损失（HL）可由多种不同的遗传因素引起。非综合征性HL是指HL在个体中作为一种孤立症状出现，而综合征性HL是指HL与其他症状或异常相关。迄今为止，已有140多个基因被确定与非综合征性HL相关，约400种遗传综合征可将HL作为临床症状之一。然而，目前尚无恢复或改善听力的基因治疗方法。因此，迫切需要阐明HL相关基因中特定突变的可能发病机制，并研究有前景的遗传性HL治疗策略。CRISPR/Cas系统的发展彻底改变了基因组工程领域，它已成为促进遗传性HL研究的一种有效且经济高效的工具。此外，多项体内研究已证明CRISPR/Cas介导的治疗对特定遗传性HL具有治疗效果。在本综述中，我们简要介绍了CRISPR/Cas技术的进展以及对遗传性HL的认识，然后详细阐述了CRISPR/Cas技术在疾病建模和遗传性HL治疗策略方面的最新成果。此外，我们还讨论了CRISPR/Cas技术在未来临床治疗应用中面临的挑战。
