Two separate preclinical efforts reported improvements to lipid nanoparticle (LNP) performance for mRNA and gene therapies. University of Pennsylvania researchers showed crosslinked ionizable lipids (C12‑2aN) reprogram dendritic‑cell metabolism to boost vaccine potency while lowering inflammatory signals, published in Nature Materials. The redesign improved delivery to lymphoid organs in mice and human cell assays. A second study from Biohub researchers found that physiological media and specific amino acid supplementation markedly improved in‑vivo LNP uptake; supplementing methionine or arginine doubled delivery in model systems and clarified how cell metabolic state controls nanoparticle reception. These mechanistic findings highlight that both LNP chemistry and host metabolic context determine therapeutic efficiency. Collectively, the work points to iterative chemistry and formulation strategies that can increase on‑target activity while reducing side effects—key levers for next‑generation mRNA vaccines and in‑vivo gene‑editing therapies.