G9-1 is a nitric oxide (NO)-inhibitory ionizable lipid designed for anti-inflammatory mRNA delivery. Derived from the potent NO inhibitor G9, it retains the ability to suppress macrophage-driven inflammation while enabling efficient mRNA encapsulation and lung-targeted delivery. In a murine acute lung injury model, G9-1 lipid nanoparticles (LNPs) loaded with IL-10 mRNA demonstrated synergistic therapeutic effects by reducing inflammatory cell infiltration, suppressing pro-inflammatory cytokines, and improving systemic tissue injury markers. With its intrinsic immunomodulatory activity and preferential targeting of lung-resident cells, G9-1 represents a promising platform for safer and more effective mRNA therapeutics in inflammatory disorders.
