Wang Dawei, Zhang YiZhan, Zhang Jinning, Zhao JiaJun
Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, China; Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging, Ministry of Education, Shandong Provincial Hospital Affiliated to Shandong First Medical University, China; "Chuangxin China" Innovation Base of stem cell and Gene Therapy for endocrine Metabolic diseases, China; Shandong Engineering Research Center of Stem Cell and Gene Therapy for Endocrine and Metabolic Diseases, Jinan, Shandong 250021, China.
Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging, Ministry of Education, Shandong Provincial Hospital Affiliated to Shandong First Medical University, China; Department of Endocrinology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong 250021, China; "Chuangxin China" Innovation Base of stem cell and Gene Therapy for endocrine Metabolic diseases, China; Shandong Engineering Research Center of Stem Cell and Gene Therapy for Endocrine and Metabolic Diseases, Jinan, Shandong 250021, China.
Mutat Res Rev Mutat Res. 2024 Jul-Dec;794:108515. doi: 10.1016/j.mrrev.2024.108515. Epub 2024 Oct 23.
Single nucleotide variants (SNVs) constitute the most frequent variants that cause human genetic diseases. Base editors (BEs) comprise a new generation of CRISPR-based technologies, which are considered to have a promising future for curing genetic diseases caused by SNVs as they enable the direct and irreversible correction of base mutations. Two of the early types of BEs, cytosine base editor (CBE) and adenine base editor (ABE), mediate C-to-T, T-to-C, A-to-G, and G-to-A base transition mutations. Together, these represent half of all the known disease-associated SNVs. However, the remaining transversion (i.e., purine-pyrimidine) mutations cannot be restored by direct deamination and so these require the replacement of the entire base. Recently, a variety of base transversion editors were developed and so these add to the currently available BEs enabling the correction of all types of point mutation. However, compared to the base transition editors (including CBEs and ABEs), base transversion editors are still in the early development stage. In this review, we describe the basics and advances of the various base transversion editors, highlight their limitations, and discuss their potential for treating human diseases.
单核苷酸变异（SNV）是导致人类遗传疾病最常见的变异类型。碱基编辑器（BE）是新一代基于CRISPR的技术，由于能够直接且不可逆地纠正碱基突变，因此在治疗由SNV引起的遗传疾病方面被认为具有广阔前景。早期的两种碱基编辑器，胞嘧啶碱基编辑器（CBE）和腺嘌呤碱基编辑器（ABE），介导C到T、T到C、A到G和G到A的碱基转换突变。这些突变加起来占所有已知疾病相关SNV的一半。然而，其余的颠换（即嘌呤-嘧啶）突变无法通过直接脱氨恢复，因此需要替换整个碱基。最近，多种碱基颠换编辑器被开发出来，这增加了目前可用的碱基编辑器类型，能够纠正所有类型的点突变。然而，与碱基转换编辑器（包括CBE和ABE）相比，碱基颠换编辑器仍处于早期开发阶段。在这篇综述中，我们描述了各种碱基颠换编辑器的基本原理和进展，强调了它们的局限性，并讨论了它们在治疗人类疾病方面的潜力。
