A review of application of base editing for the treatment of inner ear disorders

• 作者: Kang Wen Sun Zhuoer Tao Yong Wu Hao Zhao Xingle
• 来源期刊: 生物组学研究杂志（英文）
• 关键词: base editing base editor CRISPR deafness treatment gene editing gene therapy hearing inner ear
• 年，卷（期）: 2020,（2）
• 所属期刊栏目: Review Article
• 页码范围: 66-71
• 页数: 6页
• 语种: 中文
• DOI: 10.1097/JBR.0000000000000040

摘要

The development of applications for the CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated nuclease 9) system has increased greatly in recent years, especially in the area of gene therapy by efficient in vivo genome editing. Although great success has been achieved in repairing and rewriting genomes through homology-directed repair coupled with Cas9 nuclease cleavage, its in vivo efficiency is insufficient for gene therapy. Base editing is a next-generation genome-editing tool that does not involve double-stranded DNA breaks and uses components of the CRISPR system together with other enzymes to make point mutations directly in cellular DNA or RNA. Base editors, composed of an engineered deaminase and a catalytically impaired CRISPR/Cas9 variant, are powerful tools for targeted base editing in cells and organisms. In non-dividing cells, base editors can directly transform one base or base pair into another, efficiently installing a point mutation. Undesired by-products of editing are seldom generated during this procedure. Herein we review the different base-editing platforms, including their deaminase recruitment strategies and editing outcomes, and the in vivo delivery of base editors. Additionally, we summarize therapeutic applications of base editing in disorders of the inner ear.