CRISPR/Cas9: Genethon Unveils an Innovative Strategy to Increase Utrophin in Duchenne Muscular Dystrophy

In a study published in March 2026 in the journal Molecular Therapy, scientists from the “ Gene Editing ” team , led by Dr. Mario Amendola, unveil an innovative approach to genome editing aimed at sustainably increasing utrophin expression. This protein could compensate for the absence of dystrophin in people with Duchenne muscular dystrophy (DMD), a severe neuromuscular disease for which there is still no cure.

This publication once again highlights the excellence of Genethon’s teams in designing next-generation gene therapy approaches and their commitment to developing therapeutic solutions for all patients, regardless of their mutations.

A strategy that unlocks UTRN gene expression

Rather than directly targeting the DMD gene, the team focused on a key regulatory mechanism. The researchers used CRISPR-Cas9 to inactivate a binding site of the microRNA Let-7c, a small molecule that normally blocks UTRN gene expression.

Result: utrophin is “unlocked” and its expression naturally increases, by 2 to 3 times, in human DMD cells and in human muscles reproduced in 3D in vitro and derived from myoblasts.

Benefits observed from the laboratory to the mouse model

The effects of this strategy have been confirmed in several preclinical models:

• Human muscles grown in 3D in vitro (organoids): improved calcium regulation and contractile force.
• Mdx mice (DMD model): increased utrophin levels in multiple muscles, reduced fibrosis, and improved functional parameters following local or systemic administration of AAV9.

This work brings together a unique set of internal expertise: genome editing, viral bioproduction, histology, advanced imaging, and functional assessments. A strong demonstration of Genethon’s collective excellence.

Toward a potentially universal strategy for DMD patients

Because it does not depend on any specific mutation in the DMD gene, this approach could be applicable to all patients, a major challenge in a disease with highly varied genetic profiles.

“This genome editing strategy demonstrates that by removing a single molecular barrier, we can reactivate a natural muscle protection mechanism. It paves the way for more universal, longer-lasting gene therapies that fully complement the dystrophin or microdystrophin based approaches already in development.” — Dr. Mario Amendola, Head of the Gene Editing Team.