Researchers published two complementary Nature Biotechnology reports presenting in vivo methods to quantify endosomal escape of lipid nanoparticles (LNPs). One uses a lysosomal barcoding strategy to measure escape performance of branched ionizable lipids in liver delivery; the other reports an independent in vivo assay that quantifies endosomal release efficiency to inform LNP design. Both teams showed that endosomal escape—not uptake alone—drives functional delivery of nucleic acids in vivo. The assays provide actionable metrics for screening lipids, formulations and structure–activity relationships that were previously inferred only from in vitro models. These tools give developers a new, data-driven basis to prioritize ionizable lipid chemistries and formulations for hepatic and extrahepatic targets and should accelerate translation of mRNA, base editing and gene insertion therapies by reducing the empirical burden of LNP optimization.