Impact of Chromatin Organization and Epigenetics on CRISPR-Cas and TALEN Genome Editing.

IF 3.7 2区生物学 Q1 BIOCHEMICAL RESEARCH METHODS ACS Synthetic Biology Pub Date : 2024-09-24 DOI:10.1021/acssynbio.4c00099

Surbhi Jain, Guanhua Xun, Huimin Zhao

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引用次数: 0

Abstract

DNA lies at the heart of the central dogma of life. Altering DNA can modify the flow of information in fundamental cellular processes such as transcription and translation. The ability to precisely manipulate DNA has led to remarkable advances in treating incurable human genetic ailments and has changed the landscape of biological research. Genome editors such as CRISPR-Cas nucleases and TALENs have become ubiquitous tools in basic and applied biological research and have been translated to the clinic to treat patients. The specificity and modularity of these genome editors have made it possible to efficiently engineer genomic DNA; however, underlying principles governing editing outcomes in eukaryotes are still being uncovered. Editing efficiency can vary from cell type to cell type for the same DNA target sequence, necessitating de novo design and validation efforts. Chromatin structure and epigenetic modifications have been shown to affect the activity of genome editors because of the role they play in hierarchical organization of the underlying DNA. Understanding the nuclear search mechanism of genome editors and their molecular interactions with higher order chromatin will lead to improved models for predicting precise genome editing outcomes. Insights from such studies will unlock the entire genome to be engineered for the creation of novel therapies to treat critical illnesses.

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染色质组织和表观遗传学对 CRISPR-Cas 和 TALEN 基因组编辑的影响。

DNA 是生命基本原理的核心。改变 DNA 可以改变转录和翻译等基本细胞过程中的信息流。精确操纵 DNA 的能力在治疗人类无法治愈的遗传疾病方面取得了显著进展，并改变了生物研究的格局。CRISPR-Cas 核酸酶和 TALENs 等基因组编辑器已成为基础和应用生物学研究中无处不在的工具，并已应用于临床治疗病人。这些基因组编辑器的特异性和模块化使得高效地设计基因组 DNA 成为可能；然而，真核生物编辑结果的基本原理仍在研究之中。对于相同的 DNA 目标序列，不同细胞类型的编辑效率可能会有所不同，因此有必要进行全新设计和验证。染色质结构和表观遗传修饰已被证明会影响基因组编辑器的活性，因为它们在底层 DNA 的分层组织中发挥作用。了解基因组编辑器的核搜索机制及其与高阶染色质的分子相互作用，将有助于改进预测精确基因组编辑结果的模型。从这些研究中获得的洞察力将开启整个基因组的工程设计，从而创造出治疗危重疾病的新型疗法。

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来源期刊

ACS Synthetic Biology 生物-

CiteScore

8.00

自引率

10.60%

发文量

380

审稿时长

6-12 weeks

期刊介绍： The journal is particularly interested in studies on the design and synthesis of new genetic circuits and gene products; computational methods in the design of systems; and integrative applied approaches to understanding disease and metabolism. Topics may include, but are not limited to: Design and optimization of genetic systems Genetic circuit design and their principles for their organization into programs Computational methods to aid the design of genetic systems Experimental methods to quantify genetic parts, circuits, and metabolic fluxes Genetic parts libraries: their creation, analysis, and ontological representation Protein engineering including computational design Metabolic engineering and cellular manufacturing, including biomass conversion Natural product access, engineering, and production Creative and innovative applications of cellular programming Medical applications, tissue engineering, and the programming of therapeutic cells Minimal cell design and construction Genomics and genome replacement strategies Viral engineering Automated and robotic assembly platforms for synthetic biology DNA synthesis methodologies Metagenomics and synthetic metagenomic analysis Bioinformatics applied to gene discovery, chemoinformatics, and pathway construction Gene optimization Methods for genome-scale measurements of transcription and metabolomics Systems biology and methods to integrate multiple data sources in vitro and cell-free synthetic biology and molecular programming Nucleic acid engineering.