Gene editing and Rett syndrome: does it make the cut?

Coorey, Bronte, Haase, Florencia, Ellaway, Carolyn, Clarke, Angus ORCID: https://orcid.org/0000-0002-1200-9286, Lisowski, Leszek and Gold, Wendy A. 2022. Gene editing and Rett syndrome: does it make the cut? The CRISPR Journal 5 (4) , pp. 490-499. 10.1089/crispr.2022.0020

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Abstract

Rett syndrome (RTT) is a rare neurogenetic disorder caused by pathogenic variants of the Methyl CpG binding protein 2 (MECP2) gene. The RTT is characterized by apparent normal early development followed by regression of communicative and fine motor skills. Comorbidities include epilepsy, severe cognitive impairment, and autonomic and motor dysfunction. Despite almost 60 clinical trials and the promise of a gene therapy, no cure has yet emerged with treatment remaining symptomatic. Advances in understanding RTT has provided insight into the complexity and exquisite control of MECP2 expression, where loss of expression leads to RTT and overexpression leads to MECP2 duplication syndrome. Therapy development requires regulated expression that matches the spatiotemporal endogenous expression of MECP2 in the brain. Gene editing has revolutionized gene therapy and promises an exciting strategy for many incurable monogenic disorders, including RTT, by editing the native locus and retaining endogenous gene expression. Here, we review the literature on the currently available editing technologies and discuss their limitations and applicability to the treatment of RTT.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Publisher:	Mary Ann Liebert
ISSN:	2573-1599
Date of First Compliant Deposit:	31 August 2022
Date of Acceptance:	26 July 2022
Last Modified:	30 Nov 2024 14:30
URI:	https://orca.cardiff.ac.uk/id/eprint/152262

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