Perera Bambarendage P U, Morgan Rachel K, Polemi Katelyn M, Sala-Hamrick Kimmie E, Svoboda Laurie K, Dolinoy Dana C
School of Public Health, Department of Environmental Health Sciences, University of Michigan, Ann Arbor, MI, USA.
School of Public Health, Department of Nutritional Sciences, University of Michigan, Ann Arbor, MI, USA.
Curr Environ Health Rep. 2022 Dec;9(4):650-660. doi: 10.1007/s40572-022-00372-6. Epub 2022 Aug 2.
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.
表观基因组可响应环境刺激调节基因表达。对表观基因组的修饰具有潜在的可逆性，使其成为减轻环境暴露对人类健康影响的一种有前景的治疗方法。本综述详细介绍了目前可用的基因组和表观基因组编辑技术，并强调了非编码RNA（ncRNA），包括piRNA，作为靶向表观基因组编辑的潜在工具。
锌指核酸酶（ZFN）、转录激活样效应核酸酶（TALEN）和成簇规律间隔短回文重复序列（CRISPR）相关核酸酶（CRISPR/Cas）的研究显著推动了基因组编辑技术的发展，在基因研究和靶向治疗方面具有广阔前景。最初的表观基因组定向疗法依赖于全局修饰，特异性有限。基于当前的基因组编辑工具改进而来的锌指蛋白（ZFP）、TALE和CRISPR/核酸酶失活的Cas（dCas）系统现在可实现位点特异性表观基因组编辑，在环境卫生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选所需时间限制了它们的应用。
ncRNA作为一种多功能生物标志物，具有特征明确的调控机制，可轻松用于编辑表观基因组。例如，可设计种系PIWI相互作用RNA（piRNA）的转座子沉默机制，使其特异性甲基化特定基因，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研究为风险评估提供信息，并作为潜在的干预方式，以减轻生命后期环境诱导的不良健康后果。
