Antisense oligonucleotide selection scheme for rare Duchenne muscular dystrophy mutations: Application to DMD exon 16 skipping

In Duchenne muscular dystrophy (DMD), a lethal X-linked disorder affecting 1:5,000 males, four AON therapies have received accelerated approval. However, these treatments are applicable to only 27% of patients, leaving most individuals with rare mutations without therapeutic options.

Here, we outline a methodology to identify relevant AONs for such populations. This approach aims to prequalify candidates and eliminate unsuitable leads before animal testing, reducing development time and costs. Following high-throughput screening, selected AONs are assessed for intravenous delivery compatibility and serum protein binding to support model selection and forecast human pharmacokinetics.