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Transgenic Research

, Volume 27, Issue 6, pp 489–509 | Cite as

In vivo epigenome editing and transcriptional modulation using CRISPR technology

  • Cia-Hin Lau
  • Yousin Suh
Review

Abstract

The rapid advancement of CRISPR technology has enabled targeted epigenome editing and transcriptional modulation in the native chromatin context. However, only a few studies have reported the successful editing of the epigenome in adult animals in contrast to the rapidly growing number of in vivo genome editing over the past few years. In this review, we discuss the challenges facing in vivo epigenome editing and new strategies to overcome the huddles. The biggest challenge has been the difficulty in packaging dCas9 fusion proteins required for manipulation of epigenome into the adeno-associated virus (AAV) delivery vehicle. We review the strategies to address the AAV packaging issue, including small dCas9 orthologues, truncated dCas9 mutants, a split-dCas9 system, and potent truncated effector domains. We discuss the dCas9 conjugation strategies to recruit endogenous chromatin modifiers and remodelers to specific genomic loci, and recently developed methods to recruit multiple copies of the dCas9 fusion protein, or to simultaneous express multiple gRNAs for robust epigenome editing or synergistic transcriptional modulation. The use of Cre-inducible dCas9-expressing mice or a genetic cross between dCas9- and sgRNA-expressing flies has also helped overcome the transgene delivery issue. We provide perspective on how a combination use of these strategies can facilitate in vivo epigenome editing and transcriptional modulation.

Keywords

Adeno-associated virus Cis-regulatory elements CRISPR activation CRISPR interference Epigenome editing Epigenetic regulation 

Notes

Acknowledgements

This work was funded by NIH Grants (AG017242, GM104459, AG056278, and CA180126) and by the Glenn Center for the Biology of Human Aging (Paul Glenn Foundation for Medical Research) (Suh).

Compliance with ethical standards

Conflict of interest

The author declares that they have no conflict of interest.

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Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  1. 1.Department of Biomedical EngineeringCity University of Hong KongHong KongChina
  2. 2.Department of Genetics, Michael F. Price CenterAlbert Einstein College of MedicineBronxUSA
  3. 3.Department of MedicineAlbert Einstein College of MedicineBronxUSA
  4. 4.Department of Ophthalmology and Visual SciencesAlbert Einstein College of MedicineBronxUSA

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