Rapid and scalable personalized ASO screening in patient-derived organoids.

ABSTRACT: Personalized antisense oligonucleotides (ASOs) have achieved positive results in the treatment of rare genetic disease¹. As clinical sequencing technologies continue to advance, the ability to identify patients with rare disease harbouring pathogenic genetic variants amenable to this therapeutic strategy will probably improve. Here we describe a scalable platform for generating patient-derived cellular models and demonstrate that these personalized models can be used for preclinical evaluation of patient-specific ASOs. We describe protocols for delivery of ASOs to patient-derived organoid models and confirm reversal of disease-associated phenotypes in cardiac organoids derived from a patient with Duchenne muscular dystrophy (DMD) with a structural deletion in the gene encoding d

SUBMITTER: Means JC 

PROVIDER: S-EPMC11798851 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature