Fully automated fast-flow synthesis of antisense phosphorodiamidate morpholino oligomers

Abstract Rapid development of antisense therapies can enable on-demand responses to new viral pathogens and make personalized medicine for genetic diseases practical. Antisense phosphorodiamidate morpholino oligomers (PMOs) are promising candidates fill such a role, but their challenging synthesis limits widespread application. To rapidly prototype potential PMO drug candidates, we report fully automated flow-based oligonucleotide synthesizer. Our optimized platform reduces coupling times by up 22-fold compared previously reported methods. We demonstrate the power our technology with milligram quantities three candidate therapeutic sequences an unserved class Duchenne muscular dystrophy (DMD). further test platform, synthesize that targets genomic mRNA SARS-CoV-2 its antiviral effects. This could find broad application not only in designing DMD therapeutics, also rapid treat emerging diseases.