Increasing Specificity of Targeted DNA Methylation Editing by Non-Enzymatic CRISPR/dCas9-Based Steric Hindrance

As advances in genome engineering inch the technology towards wider clinical use—slowed by technical and ethical hurdles—a newer offshoot, termed “epigenome engineering”, offers the ability to correct disease-causing changes in the DNA without changing its sequence and, thus, without some of the unf...

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Main Authors: Daniel M. Sapozhnikov, Moshe Szyf
Format: Article
Language:English
Published: MDPI AG 2023-04-01
Series:Biomedicines
Subjects:
Online Access:https://www.mdpi.com/2227-9059/11/5/1238
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author Daniel M. Sapozhnikov
Moshe Szyf
author_facet Daniel M. Sapozhnikov
Moshe Szyf
author_sort Daniel M. Sapozhnikov
collection DOAJ
description As advances in genome engineering inch the technology towards wider clinical use—slowed by technical and ethical hurdles—a newer offshoot, termed “epigenome engineering”, offers the ability to correct disease-causing changes in the DNA without changing its sequence and, thus, without some of the unfavorable correlates of doing so. In this review, we note some of the shortcomings of epigenetic editing technology—specifically the risks involved in the introduction of epigenetic enzymes—and highlight an alternative epigenetic editing strategy using physical occlusion to modify epigenetic marks at target sites without a requirement for any epigenetic enzyme. This may prove to be a safer alternative for more specific epigenetic editing.
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spelling doaj.art-5e9d4a9712a240ec96162e4833ef4cdc2023-11-18T00:34:03ZengMDPI AGBiomedicines2227-90592023-04-01115123810.3390/biomedicines11051238Increasing Specificity of Targeted DNA Methylation Editing by Non-Enzymatic CRISPR/dCas9-Based Steric HindranceDaniel M. Sapozhnikov0Moshe Szyf1Department of Pharmacology and Therapeutics, Faculty of Medicine and Health Sciences, McGill University, Montreal, QC H3G 1Y6, CanadaDepartment of Pharmacology and Therapeutics, Faculty of Medicine and Health Sciences, McGill University, Montreal, QC H3G 1Y6, CanadaAs advances in genome engineering inch the technology towards wider clinical use—slowed by technical and ethical hurdles—a newer offshoot, termed “epigenome engineering”, offers the ability to correct disease-causing changes in the DNA without changing its sequence and, thus, without some of the unfavorable correlates of doing so. In this review, we note some of the shortcomings of epigenetic editing technology—specifically the risks involved in the introduction of epigenetic enzymes—and highlight an alternative epigenetic editing strategy using physical occlusion to modify epigenetic marks at target sites without a requirement for any epigenetic enzyme. This may prove to be a safer alternative for more specific epigenetic editing.https://www.mdpi.com/2227-9059/11/5/1238epigenetic editingDNA methylationCRISPR/Cas9dCas9DNMT1DNMT3A
spellingShingle Daniel M. Sapozhnikov
Moshe Szyf
Increasing Specificity of Targeted DNA Methylation Editing by Non-Enzymatic CRISPR/dCas9-Based Steric Hindrance
Biomedicines
epigenetic editing
DNA methylation
CRISPR/Cas9
dCas9
DNMT1
DNMT3A
title Increasing Specificity of Targeted DNA Methylation Editing by Non-Enzymatic CRISPR/dCas9-Based Steric Hindrance
title_full Increasing Specificity of Targeted DNA Methylation Editing by Non-Enzymatic CRISPR/dCas9-Based Steric Hindrance
title_fullStr Increasing Specificity of Targeted DNA Methylation Editing by Non-Enzymatic CRISPR/dCas9-Based Steric Hindrance
title_full_unstemmed Increasing Specificity of Targeted DNA Methylation Editing by Non-Enzymatic CRISPR/dCas9-Based Steric Hindrance
title_short Increasing Specificity of Targeted DNA Methylation Editing by Non-Enzymatic CRISPR/dCas9-Based Steric Hindrance
title_sort increasing specificity of targeted dna methylation editing by non enzymatic crispr dcas9 based steric hindrance
topic epigenetic editing
DNA methylation
CRISPR/Cas9
dCas9
DNMT1
DNMT3A
url https://www.mdpi.com/2227-9059/11/5/1238
work_keys_str_mv AT danielmsapozhnikov increasingspecificityoftargeteddnamethylationeditingbynonenzymaticcrisprdcas9basedsterichindrance
AT mosheszyf increasingspecificityoftargeteddnamethylationeditingbynonenzymaticcrisprdcas9basedsterichindrance