Nature Reviews Drug Discovery, Published online: 09 September 2026; doi:10.1038/d41573-026-00125-2 To unlock the ‘plug-and-play’ potential of extrahepatic delivery of oligonucleotide-based drugs, the field must bridge the gap between preclinical promise and clinical reality. Here, we outline an industry-grade quality framework to eliminate methodological artifacts and ensure the translational and commercial viability of novel platforms.