A study published in Molecular Therapy – Nucleic Acids describes a method designed to accelerate the selection of antisense oligonucleotides for rare and ultra-rare mutations causing Duchenne muscular dystrophy. Applied to exon 16 skipping, the approach led to the identification of the preclinical candidate DMD-SQY16.

Guyancourt, September 1, 2026

SQY Therapeutics today announced the publication of a study on the development of antisense therapies for patients with Duchenne muscular dystrophy (DMD) who carry very rare mutations.

Entitled “Antisense oligonucleotide selection scheme for rare Duchenne muscular dystrophy mutations: Application to DMD exon 16 skipping”, the article describes a method for more rapidly identifying effective antisense oligonucleotides with a safety profile suitable for further development.

The study, conducted by SQY Therapeutics in collaboration with the University of Cologne and the University of Copenhagen, was published in the scientific journal Molecular Therapy – Nucleic Acids.

Addressing the needs of patients with ultra-rare mutations

Currently approved antisense exon-skipping therapies are applicable to only a subset of patients with DMD. Developing a treatment for patients with rare or ultra-rare mutations is particularly challenging: the patient populations are extremely small, relevant experimental models are often unavailable, and preclinical development pathways are lengthy and costly.

The researchers sought to establish a strategy for selecting a therapeutic candidate more efficiently while eliminating, at an early stage, molecules likely to pose risks when administered intravenously.

The approach is intended to reduce timelines, costs and reliance on animal models with limited relevance, thereby making treatment development more feasible for very small patient populations.

DMD-SQY16: a preclinical candidate for exon 16 skipping

To demonstrate the feasibility of this approach, the researchers focused on an ultra-rare mutation located in exon 16 of the DMD gene.

A library of 59 antisense oligonucleotides based on SQY Therapeutics’ tcDNA technology was designed and evaluated. Candidates were initially screened for their ability to restore dystrophin expression in patient-derived muscle cells.

The most active molecules then underwent early assessments of their behavior in plasma, potential effects on coagulation and complement activation, and interactions with plasma proteins.

This selection process identified DMD-SQY16. Another oligonucleotide, although more active in certain assays, was excluded because of unfavorable coagulation findings. This result illustrates a core principle of the method: the best candidate is not necessarily the most potent, but the one offering the best balance of efficacy and safety.

Dystrophin restoration confirmed across multiple models

DMD-SQY16 was subsequently evaluated in mice and in a pilot non-human primate study. Following intravenous administration, the candidate reached skeletal, respiratory and cardiac muscles, where it induced exon 16 skipping.

In the pilot non-human primate study, no significant findings affecting coagulation, complement activation, or key hepatic, renal and hematological parameters were observed during four weeks of treatment. These results remain preliminary and will need to be confirmed in the regulatory toxicology studies required before any clinical use.

The efficacy of DMD-SQY16 was also investigated in three-dimensional human muscle models derived from patient cells. Treatment produced dose-dependent exon 16 skipping and dystrophin restoration, reaching up to 47% of the level observed in healthy muscle under the highest experimental exposure conditions.

Transcriptomic and proteomic analyses also showed partial improvement in several molecular signatures characteristic of dystrophic muscle, including pathways related to inflammation, cytoskeletal organization, muscle contraction, mitochondrial function and the extracellular matrix.

Toward individualized n-of-1 development pathways

Beyond DMD-SQY16, the publication establishes proof of concept for developing treatments for extremely small patient populations.

The method could enable more rapid prequalification of antisense oligonucleotides tailored to other rare mutations by combining patient-derived cells, 3D human muscle models and early risk assessment.

“Patients with ultra-rare mutations should not be excluded from therapeutic opportunities simply because their numbers do not support a conventional pharmaceutical development pathway. This study shows that a structured scientific approach can identify a candidate tailored to a very rare mutation while incorporating efficacy and safety requirements from the earliest stages.” Luis Garcia, President of SQY Therapeutics

Subject to completion of all required regulatory steps, this approach could ultimately help enable compassionate use or individualized n-of-1 clinical trials.

It therefore opens a new avenue: developing potential treatments not only for the most frequent mutations, but also for patients whose mutation is currently considered too rare to justify a traditional therapeutic development program.

A preclinical program requiring further development

DMD-SQY16 remains a preclinical candidate. The published findings do not yet support administration to a patient.

Additional studies, including short- and long-term regulatory toxicology studies, are essential to establish its safety profile, therapeutic window and the conditions required for potential clinical development.

Publication reference

Marine Geoffroy-Guiraud et al.
“Antisense oligonucleotide selection scheme for rare Duchenne muscular dystrophy mutations: Application to DMD exon 16 skipping”
Molecular Therapy – Nucleic Acids, Volume 37, September 2026
https://doi.org/10.1016/j.omtn.2026.103048

About SQY Therapeutics

SQY Therapeutics is a French biotechnology company specializing in the development of next-generation antisense oligonucleotides for the treatment of neuromuscular and rare diseases.
Building on research conducted at the University of Versailles Saint-Quentin-en-Yvelines, the company is developing a platform based on tcDNA technology, designed to enhance the systemic distribution of antisense oligonucleotides.
SQY Therapeutics is notably advancing SQY51 through clinical development in Duchenne muscular dystrophy.