On RNA-programmable gene modulation as a versatile set of principles targeting muscular dystrophies.

Publisher: Cell Press Country of Publication: United States NLM ID: 100890581 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1525-0024 (Electronic) Linking ISSN: 15250016 NLM ISO Abbreviation: Mol Ther Subsets: MEDLINE

Publication: 2017- : Cambridge, MA : Cell Press
Original Publication: San Diego, CA : Academic Press, 2000-

Gene Editing*/methods ; CRISPR-Cas Systems* ; Muscular Dystrophies*/therapy ; Muscular Dystrophies*/genetics ; Genetic Therapy*/methods ; Epigenesis, Genetic*; Humans ; Animals ; RNA/genetics

The repurposing of RNA-programmable CRISPR systems from genome editing into epigenome editing tools is gaining pace, including in research and development efforts directed at tackling human disorders. This momentum stems from the increasing knowledge regarding the epigenetic factors and networks underlying cell physiology and disease etiology and from the growing realization that genome editing principles involving chromosomal breaks generated by programmable nucleases are prone to unpredictable genetic changes and outcomes. Hence, engineered CRISPR systems are serving as versatile DNA-targeting scaffolds for heterologous and synthetic effector domains that, via locally recruiting transcription factors and chromatin remodeling complexes, seek interfering with loss-of-function and gain-of-function processes underlying recessive and dominant disorders, respectively. Here, after providing an overview about epigenetic drugs and CRISPR-Cas-based activation and interference platforms, we cover the testing of these platforms in the context of molecular therapies for muscular dystrophies. Finally, we examine attributes, obstacles, and deployment opportunities for CRISPR-based epigenetic modulating technologies.
Competing Interests: Declaration of interests The authors declare no competing interests.
(Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

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Keywords: CRISPR activation; CRISPR interference; Duchenne muscular dystrophy; disease-modifying genes; epigenetic editors; epigenome editing; muscular dystrophies

63231-63-0 (RNA)

Date Created: 20240822 Date Completed: 20241107 Latest Revision: 20241121

20241121

PMC11573585

10.1016/j.ymthe.2024.08.016

39169620