Guyancourt, January 30, 2026 – SQY Therapeutics, a biotechnology company specializing in the development of therapies using tricyclo-DNA antisense oligonucleotides (tcDNA-ASO), today announces the results of a preclinical study published on January 22, 2026, in NAR Molecular Medicine. This study, conducted in collaboration with a team from the PHARMAColigo unit at UVSQ, demonstrates the feasibility of pulmonary administration of the antisense oligonucleotide SQY51, a tcDNA-ASO (currently in clinical trials by SQY Therapeutics for Duchenne muscular dystrophy). This route of administration enables effective systemic distribution, prolonged bioavailability, and excellent tolerance, paving the way for a less invasive alternative to intravenous (IV) injection for the treatment of chronic diseases. .
In this study, researchers evaluated the intratracheal (IT) instillation of SQY51 in mice, compared to intravenous (IV) administration. A single pulmonary dose was administered to analyze pharmacokinetics, biodistribution, tissue localization, and immunological effects. The results show that intratracheal administration of SQY51 in mice allows systemic absorption through the lungs, with a bioavailability of 34.4%, comparable to standards for pulmonary therapies.
Compared to IV injection, the IT route offers a lower maximum plasma concentration, slower clearance, and prolonged detection (up to 48 hours), potentially reducing renal burden and improving tolerance.
SQY51 accumulates more in the lungs after IT administration, while still reaching target organs such as the heart, diaphragm, and kidneys, albeit at lower levels than those observed with the IV route.
No significant inflammation or alteration of lung architecture was observed, confirming the safety of this administration route.
SQY51 is internalized by alveolar macrophages (marked CD68+ and CD11b+) and localized in lysosomes, suggesting an efficient endocytosis mechanism without triggering a pro-inflammatory response.
Thérèse Deramaudt, lead author of the study and researcher at UVSQ, states: “This study validates pulmonary administration as a promising route for tcDNA-ASO therapies. Not only does it enable effective systemic distribution, but it also offers a gentler alternative for patients, which is crucial for chronic diseases like DMD.“
Pulmonary administration of tcDNA-ASO could revolutionize the management of genetic diseases, such as DMD, by providing a non-invasive method that improves patients’ quality of life, offers sustained systemic distribution optimizing therapeutic efficacy, and has an enhanced safety profile, with a potential reduction in renal and inflammatory side effects. Luis Garcia, President of SQY Therapeutics, adds: “These results strengthen our belief that tcDNA-ASO can transform the therapeutic landscape for genetic diseases. We are eager to continue the clinical development of SQY51 to make it a reality for patients.”
SQY Therapeutics is now preparing new studies to evaluate the long-term efficacy of IT administration. This work opens important perspectives for the development and systemic administration of tcDNA-ASO.
About SQY Therapeutics
SQY Therapeutics is a French biotechnology company specializing in the development of antisense oligonucleotide (ASO) therapies for the treatment of genetic diseases, particularly Duchenne muscular dystrophy. Founded by parents of affected children and researchers, the company uses a unique technological platform based on tricyclo-DNA (tcDNA-ASO) to design molecules capable of correcting certain genetic mutations at the messenger RNA level. SQY Therapeutics entered the clinical trial phase in 2023 and continues to develop its first drug candidate, SQY51, a next-generation antisense oligonucleotide (tcDNA-ASO) for the treatment of Duchenne muscular dystrophy in 12 patients eligible for the exon-51 skipping therapeutic approach of the mutated DMD gene (Phase I/IIa clinical trial AVANCE-1, conducted at R. Poincaré Hospital AP-HP – UFR Simone Veil – Santé).
About PHARMACOligo
PHARMACOligo is a translational research unit at the Université Versailles Saint Quentin (UR 20261 UVSQ), led by Professors Helge Amthor and Marcel Bonay. Its research spans from fundamental myology to the development of new therapeutic modalities for neuromuscular diseases. The ‘triad’ of PHARMACOligo, SQY Therapeutics, and the Raymond-Poincaré University Hospital (APHP-UVSQ) forms a unique Hospital-University Ecosystem (EHU) that brings together multidisciplinary research in chemistry, biology, medicine, and clinical studies essential for developing new therapeutic modalities for diseases with unsatisfied or unsatisfactory care options.
Study Reference: Laurent, J. et al., (2026). Systemic distribution of tricyclo-DNA antisense oligonucleotide following intratracheal instillation in the mouse. NAR Molecular Medicine. DOI: 10.1093/narmme/ugag001.