The applications of CRISPR/Cas-mediated genome editing in genetic hearing loss

Abstract

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.

Advanced Omics Techniques for Understanding Cochlear Genome, Epigenome, and Transcriptome in Health and Disease

“…Therefore, the CRISPR/Cas9 technology represents a powerful tool for basic molecular studies in hearing research and a promising strategy for therapeutic approaches to SNHL [28][29][30]. In particular, CRISPR/Cas9 has been successfully applied to the creation of new in vitro and in vivo models of cochlear diseases [31]. For instance, this technology has allowed the study of genes associated with ototoxicity via the knock-out of Lim-domain only 4 (LMO4), for cisplatin, and HtrA Serine Peptidase 2 (htra2), for aminoglycosides, in vitro and in vivo models, respectively [32,33].…”

“…For instance, this technology has allowed the study of genes associated with ototoxicity via the knock-out of Lim-domain only 4 (LMO4), for cisplatin, and HtrA Serine Peptidase 2 (htra2), for aminoglycosides, in vitro and in vivo models, respectively [32,33]. It has also allowed the study of inherited hearing loss genes, such as MYO7A, CIB2, and CDH23, for Usher syndrome [31]. Moreover, zebrafish models to study genes involved in the development of the auditory system, such as POU4F3, have recently been developed based on CRISPR/Cas9 [34].…”

Advanced Omics Techniques for Understanding Cochlear Genome, Epigenome and Transcriptome in Health and Disease

“…Therefore, the CRISPR/Cas9 technology represents a powerful tool for basic molecular studies in hearing research, and a promising strategy for therapeutic approaches of SNHL [27][28][29]. In particular, CRISPR/Cas9 has been successfully applied for creating new in vitro and in vivo models of cochlear diseases [30]. For instance, this technology has allowed to study genes associated with ototoxicity, via the knock-out of Lim-domain only 4 (LMO4), for cisplatin, and HtrA Serine Peptidase 2 (htra2), for aminoglycosides, in in vitro and in vivo models respectively [31,32].…”

“…For instance, this technology has allowed to study genes associated with ototoxicity, via the knock-out of Lim-domain only 4 (LMO4), for cisplatin, and HtrA Serine Peptidase 2 (htra2), for aminoglycosides, in in vitro and in vivo models respectively [31,32]. It also allowed the study of inherited hearing loss genes, such as MYO7A, CIB2 and CDH23, for the Usher syndrome [30]. Moreover, zebrafish models to study genes involved in the development of the auditory system, such as POU4F3, have recently been developed based on CRISPR/Cas9 [33] .…”