Two independent reports introduced in vivo methods to quantify endosomal escape — the rate‑limiting step for lipid nanoparticle (LNP) delivery — and applied the assays to optimize liver-targeted formulations. Researchers developed lysosomal barcoding and related readouts to measure cytosolic release of nucleic acids in mice, enabling direct comparison of lipid chemistries and formulations in situ. The work, published in Nature Biotechnology and related outlets, identified branched ionizable lipids and formulation parameters that increase endosomal escape and hepatic potency without necessarily changing systemic exposure. Authors highlighted how these assays allow mechanistic selection of lipids for liver delivery and can accelerate preclinical screening of RNA therapeutics. For developers of mRNA vaccines, gene editing LNPs and siRNA drugs, the new tools offer a path to rationally improve efficacy and reduce dose, which could lower toxicity and manufacturing burdens. The methods also provide actionable benchmarks for industrial LNP optimization and regulatory discussions around potency assays.