环境健康科学中的piwi -相互作用RNA (piRNA)和表观遗传编辑。

IF 7.4 2区 医学 Q1 PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH Current Environmental Health Reports Pub Date : 2022-12-01 DOI:10.1007/s40572-022-00372-6
Bambarendage P U Perera, Rachel K Morgan, Katelyn M Polemi, Kimmie E Sala-Hamrick, Laurie K Svoboda, Dana C Dolinoy
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引用次数: 1

摘要

综述的目的:表观基因组在环境刺激下调节基因表达。表观基因组的修饰可能是可逆的,这使它们成为减轻环境暴露对人类健康影响的一种有希望的治疗方法。本文详细介绍了目前可用的基因组和表观基因组编辑技术,并强调了包括piRNA在内的ncRNA作为靶向表观基因组编辑的潜在工具。锌指核酸酶(ZFN)、转录激活因子样效应核酸酶(TALEN)和聚集规律间隔短回文重复(CRISPR)相关核酸酶(CRISPR/Cas)的研究显著推进了基因组编辑技术,在遗传研究和靶向治疗中具有广阔的前景。最初的表观基因组导向疗法依赖于全局修饰,特异性有限。锌指蛋白(ZFP)、TALE和CRISPR/核酸酶失活Cas (dCas)系统改编自当前的基因组编辑工具,现在赋予位点特异性表观基因组编辑功能,在环境健康科学领域具有广阔的应用前景。然而,脱靶效应的高发生率和筛查时间限制了它们的使用。未来发展:ncRNA是一种多功能生物标志物,具有良好的调控机制,可以很容易地用于编辑表观基因组。例如,可以设计种系piwi相互作用rna (piRNA)的转座子沉默机制,使其特异性地甲基化给定基因,从而克服当前全局修饰剂的缺陷。表观基因组编辑技术的未来发展将通过机制调查为风险评估提供信息,并作为潜在的干预模式,以减轻生命后期环境引起的不良健康后果。
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PIWI-Interacting RNA (piRNA) and Epigenetic Editing in Environmental Health Sciences.

PURPOSE OF REVIEW: The epigenome modulates gene expression in response to environmental stimuli. Modifications to the epigenome are potentially reversible, making them a promising therapeutic approach to mitigate environmental exposure effects on human health. This review details currently available genome and epigenome editing technologies and highlights ncRNA, including piRNA, as potential tools for targeted epigenome editing. RECENT FINDINGS: Zinc finger nuclease (ZFN), transcription activator-like effector nuclease (TALEN), and clustered regularly interspaced short palindromic repeats (CRISPR) associated nuclease (CRISPR/Cas) research has significantly advanced genome editing technology, with broad promise in genetic research and targeted therapies. Initial epigenome-directed therapies relied on global modification and suffered from limited specificity. Adapted from current genome editing tools, zinc finger protein (ZFP), TALE, and CRISPR/nuclease-deactivated Cas (dCas) systems now confer locus-specific epigenome editing, with promising applicability in the field of environmental health sciences. However, high incidence of off-target effects and time taken for screening limit their use. FUTURE DEVELOPMENT: ncRNA serve as a versatile biomarker with well-characterized regulatory mechanisms that can easily be adapted to edit the epigenome. For instance, the transposon silencing mechanism of germline PIWI-interacting RNAs (piRNA) could be engineered to specifically methylate a given gene, overcoming pitfalls of current global modifiers. Future developments in epigenome editing technologies will inform risk assessment through mechanistic investigation and serve as potential modes of intervention to mitigate environmentally induced adverse health outcomes later in life.

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来源期刊
CiteScore
13.60
自引率
1.30%
发文量
47
期刊介绍: Current Environmental Health Reports provides up-to-date expert reviews in environmental health. The goal is to evaluate and synthesize original research in all disciplines relevant for environmental health sciences, including basic research, clinical research, epidemiology, and environmental policy.
期刊最新文献
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