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通过基于非酶CRISPR/dCas9的空间位阻提高靶向DNA甲基化编辑的特异性

Increasing Specificity of Targeted DNA Methylation Editing by Non-Enzymatic CRISPR/dCas9-Based Steric Hindrance.

作者信息

Sapozhnikov Daniel M, Szyf Moshe

机构信息

Department of Pharmacology and Therapeutics, Faculty of Medicine and Health Sciences, McGill University, Montreal, QC H3G 1Y6, Canada.

出版信息

Biomedicines. 2023 Apr 22;11(5):1238. doi: 10.3390/biomedicines11051238.

Abstract

As advances in genome engineering inch the technology towards wider clinical use-slowed by technical and ethical hurdles-a newer offshoot, termed "epigenome engineering", offers the ability to correct disease-causing changes in the DNA without changing its sequence and, thus, without some of the unfavorable correlates of doing so. In this review, we note some of the shortcomings of epigenetic editing technology-specifically the risks involved in the introduction of epigenetic enzymes-and highlight an alternative epigenetic editing strategy using physical occlusion to modify epigenetic marks at target sites without a requirement for any epigenetic enzyme. This may prove to be a safer alternative for more specific epigenetic editing.

摘要

随着基因组工程的进展推动该技术朝着更广泛的临床应用迈进——尽管受到技术和伦理障碍的阻碍——一个名为“表观基因组工程”的新分支,提供了在不改变DNA序列的情况下纠正致病DNA变化的能力,因此也避免了一些相关的不利影响。在这篇综述中,我们指出了表观遗传编辑技术的一些缺点——特别是引入表观遗传酶所涉及的风险——并强调了一种替代的表观遗传编辑策略,即使用物理阻断在目标位点修饰表观遗传标记,而无需任何表观遗传酶。这可能被证明是一种更安全的替代方法,用于更特异性的表观遗传编辑。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d41/10215309/37ab7c892fc3/biomedicines-11-01238-g001.jpg

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