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Open AccessReview

CRISPR/Cas9 Epigenome Editing Potential for Rare Imprinting Diseases: A Review

1
Laboratory of Transgenic Models of Diseases, Institute of Molecular Genetics of the CAS, v.v.i, 252 50 Vestec, Czech Republic
2
Czech Centre for Phenogenomics, Institute of Molecular Genetics of the CAS, v.v.i, 252 50 Vestec, Czech Republic
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Cells 2020, 9(4), 993; https://doi.org/10.3390/cells9040993
Received: 21 March 2020 / Revised: 14 April 2020 / Accepted: 15 April 2020 / Published: 16 April 2020
(This article belongs to the Special Issue CRISPR Genome Editing)
Imprinting diseases (IDs) are rare congenital disorders caused by aberrant dosages of imprinted genes. Rare IDs are comprised by a group of several distinct disorders that share a great deal of homology in terms of genetic etiologies and symptoms. Disruption of genetic or epigenetic mechanisms can cause issues with regulating the expression of imprinted genes, thus leading to disease. Genetic mutations affect the imprinted genes, duplications, deletions, and uniparental disomy (UPD) are reoccurring phenomena causing imprinting diseases. Epigenetic alterations on methylation marks in imprinting control centers (ICRs) also alters the expression patterns and the majority of patients with rare IDs carries intact but either silenced or overexpressed imprinted genes. Canonical CRISPR/Cas9 editing relying on double-stranded DNA break repair has little to offer in terms of therapeutics for rare IDs. Instead CRISPR/Cas9 can be used in a more sophisticated way by targeting the epigenome. Catalytically dead Cas9 (dCas9) tethered with effector enzymes such as DNA de- and methyltransferases and histone code editors in addition to systems such as CRISPRa and CRISPRi have been shown to have high epigenome editing efficiency in eukaryotic cells. This new era of CRISPR epigenome editors could arguably be a game-changer for curing and treating rare IDs by refined activation and silencing of disturbed imprinted gene expression. This review describes major CRISPR-based epigenome editors and points out their potential use in research and therapy of rare imprinting diseases. View Full-Text
Keywords: rare disease; CRISPR/Cas9; epigenome editing; transcriptome editing; genomic imprinting; Angelman syndrome; Prader-Willi syndrome; transient neonatal diabetes mellitus; Silver-Russell syndrome rare disease; CRISPR/Cas9; epigenome editing; transcriptome editing; genomic imprinting; Angelman syndrome; Prader-Willi syndrome; transient neonatal diabetes mellitus; Silver-Russell syndrome
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MDPI and ACS Style

Syding, L.A.; Nickl, P.; Kasparek, P.; Sedlacek, R. CRISPR/Cas9 Epigenome Editing Potential for Rare Imprinting Diseases: A Review. Cells 2020, 9, 993.

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