Molecular therapy. Nucleic acidsDec 2, 2025

Genetic approaches for treating Duchenne muscular dystrophy

CRISPR Gene Editing Weekly Brief ↗PubMed ↗DOI ↗

Updated Jan 3, 2026

Abstract

Currently, there are no cures for Duchenne muscular dystrophy (DMD), a severe genetic disorder.

DMD is caused by mutations in the dystrophin gene, critical for muscle structure.
Available therapies mainly alleviate symptoms rather than correct the genetic defect.
Genetic strategies like exon skipping, gene replacement, and gene editing may restore dystrophin expression.
Upregulating utrophin could serve as an alternative approach to address dystrophin deficiency.
Novel modulatory therapies may reduce the consequences of dystrophin deficiency despite not addressing the root cause.
Preclinical results and early-stage clinical success have been observed, but challenges in delivery, immune response, and long-term efficacy remain.

Simplified

Duchenne muscular dystrophy (DMD) is a severe, X-linked genetic disorder caused by mutations in thegene, which encodes dystrophin, an essential structural muscle protein. Currently, there are no cures for DMD, and available therapies primarily focus on alleviating symptoms rather than correcting the underlying genetic defect. However, restoration of a shortened version of dystrophin offers the potential for partially addressing the underlying cause of the disease. This review focuses on the promises and challenges of various genetic strategies, such as exon skipping, gene replacement, and gene editing (e.g., by CRISPR-Cas9) aimed at restoring or replacing the dystrophin expression or upregulating utrophin, a paralog of dystrophin that is primarily expressed during fetal life. Finally, novel approaches for modulatory therapies are considered. While they cannot address the cause of DMD, they offer the potential to attenuate the wide-ranging consequences of dystrophin deficiency. Although some of these interventions have demonstrated encouraging preclinical results and early-stage clinical success, challenges remain in optimizing delivery methods, addressing immune responses, and ensuring long-term therapeutic efficacy. Achieving the latter will be crucial for demonstrating the effectiveness of already registered exon-skipping strategies and gene therapy with microdystrophin, which is of utmost importance for the validity of the field. DMD

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Funding

Competing interests

A.Ł. and J.D. declare that they have no conflict of interest and have no relationships with the industry. J.S.C. is an inventor and holds intellectual property related to numerous micro- and mini-dystrophins and CK-based regulatory cassettes, and he also holds equity in and is a member of the scientific advisory board for Solid Biosciences and KineaBio.

PubMed

Genetic approaches for treating Duchenne muscular dystrophy

Abstract

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Competing interests

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Abstract

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Funding

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Related papers

You found one interesting study. We’ll send the next 7.

What Lands in Your Inbox Each Week:

Recent issues from the crispr gene editing brief