4.5 Article

PIWI-Interacting RNA (piRNA) and Epigenetic Editing in Environmental Health Sciences

期刊

CURRENT ENVIRONMENTAL HEALTH REPORTS
卷 9, 期 4, 页码 650-660

出版社

SPRINGERNATURE
DOI: 10.1007/s40572-022-00372-6

关键词

DNA methylation; Epigenome editing; Genome editing; Non-coding RNA; piRNA; Toxicoepigenetics

资金

  1. TaRGET II U01 consortium [ES026697]
  2. NIH R35 RIVER award [ES031686]
  3. Michigan Lifestage Environmental Exposures and Disease (M-LEEaD) NIEHS P30 Core Center [ES017885]
  4. Career Training in Reproductive Biology [T32 HD079342]
  5. NIEHS Transition to Independent Environmental Health Research [ES032048]
  6. UM Institutional Environmental Toxicology and Epidemiology Program Training Grant [T32 ES0077062]

向作者/读者索取更多资源

This review discusses the available genome and epigenome editing technologies, emphasizing the potential role of non-coding RNA as a tool for targeted epigenome editing. Advances in zinc finger nucleases, transcription activator-like effector nucleases, and CRISPR/Cas have significantly improved genome editing technology. Future developments in non-coding RNA have the potential to overcome the limitations of global modification and allow for locus-specific epigenome editing.
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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