Systemic distribution of tricyclo-DNA antisense oligonucleotide following intratracheal instillation in the mouse.

ABSTRACT: This study evaluated intratracheal (IT) instillation as an alternative route for systemic delivery of therapeutic tricyclo-DNA antisense oligonucleotides (tcDNA-ASOs), using the Duchenne muscular dystrophy (DMD)-targeting compound SQY51 as a model. IT administration was compared with intravenous (IV) injection by assessing pharmacokinetics, biodistribution, tissue localization, and immunological effects in mice. Fluorescent hybridization assays demonstrated that IT instillation delivered SQY51 into the bloodstream, confirming systemic absorption via the pulmonary route. Compared with IV injection, IT administration produced lower peak plasma concentrations, slower clearance, and prolonged detection. Tissue distribution analysis showed higher lung accumulation but reduced levels in the kidn

SUBMITTER: Laurent J 

PROVIDER: S-EPMC12828233 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature