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.

• Klíčová slova
• Angelman syndrome, CRISPR/Cas9, Prader-Willi syndrome, Silver-Russell syndrome, epigenome editing, genomic imprinting, rare disease, transcriptome editing, transient neonatal diabetes mellitus,
• MeSH
• Angelmanův syndrom genetika   metabolismus   MeSH
• CRISPR-Cas systémy * MeSH
• diabetes mellitus genetika   metabolismus   MeSH
• editace genu metody   MeSH
• epigeneze genetická MeSH
• epigenom účinky léků   genetika   MeSH
• genomový imprinting genetika   MeSH
• lidé MeSH
• metylace DNA MeSH
• nemoci novorozenců genetika   metabolismus   MeSH
• Praderův-Williho syndrom genetika   metabolismus   MeSH
• Silverův-Russellův syndrom genetika   metabolismus   MeSH
• vzácné nemoci genetika   metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH