Clinical data from the Phase I/II MARINA trial of delpacibart etedesiran (del‑desiran, AOC‑1001), an antibody‑siRNA conjugate targeting DMPK mRNA in myotonic dystrophy type 1 (DM1), demonstrate on‑target delivery to muscle and DMPK knockdown in humans. Investigators reported that the AOC platform enabled siRNA uptake into muscle tissue and produced molecular evidence of target engagement, as detailed in the New England Journal of Medicine. The study recorded two severe adverse events but overall showed that antibody‑mediated delivery can overcome the longstanding challenge of getting oligonucleotides into skeletal muscle. Trial leaders, including Nicholas Johnson at VCU Health, emphasized the modality’s potential to address the genetic root of DM1 rather than solely treating symptoms. If safety is managed in larger cohorts, antibody‑oligo conjugates could open a scalable path for treating muscle diseases, shifting the therapeutic landscape for disorders previously considered undruggable by systemic oligonucleotides.