Experimental & molecular medicineSep 30, 2026

Using patient-derived tumor models to test cell therapy and gene editing for restoring dystrophin

CRISPR Gene Editing Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Oct 2, 2026

Abstract

Teratomas generated from DMD patient-derived stem cells contained mesodermal derivatives, including skeletal muscle-like tissue.

Patient-derived teratomas enable the assessment of therapeutic strategies for Duchenne muscular dystrophy (DMD).
Myogenic progenitors from corrected stem cells partially restored shorter dystrophin isoforms after ex vivo transplantation.
In vivo gene editing with adenine base editor mRNA led to dose-dependent editing and restoration of shorter dystrophin isoforms.
Full-length muscle-specific dystrophin was detected in some secondary teratomas, suggesting myogenic maturation influences therapeutic outcomes.
The model supports the potential for evaluating patient-specific gene correction and dystrophin restoration strategies.

Simplified

Cell and gene therapies hold great promise for treating monogenic disorders, yet their preclinical evaluation remains limited by the lack of scalable, human-specific models. Here we establish a patient-derived teratoma xenograft platform as a proof-of-concept system to evaluate ex vivo and in vivo therapeutic strategies for Duchenne muscular dystrophy (DMD). Teratomas generated from DMD patient-derived induced pluripotent stem cells contained mesodermal derivatives, including skeletal muscle-like tissue, enabling assessment of dystrophin restoration after therapeutic intervention. For ex vivo cell therapy, myogenic progenitors derived from adenine base editor-corrected induced pluripotent stem cells were transplanted into DMD teratomas, resulting in partial restoration of shorter dystrophin isoforms but not reproducible recovery of full-length Dp427m. For in vivo gene editing, local delivery of adenine base editor mRNA encapsulated in lipid nanoparticles induced dose-dependent editing and restoration of shorter dystrophin isoforms, including Dp71. Full-length, muscle-specific Dp427m was detected only in a subset of sequentially matured secondary teratomas with enriched muscle differentiation, indicating that myogenic maturation is a critical determinant of this therapeutic readout. Together, these findings support patient-derived DMD teratomas as an exploratory humanized platform for evaluating patient-specific gene correction and dystrophin isoform restoration, while highlighting the need for further optimization to reproducibly model full-length Dp427m recovery.

Full Text

Full text is available at the source.

View Full Text ↗

Using patient-derived tumor models to test cell therapy and gene editing for restoring dystrophin

Abstract

Full Text

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