cGASΔN-LNP

**cGASΔN-LNP** is a lipid nanoparticle (LNP) formulation encapsulating mRNA encoding cGAS∆N, an active mutant of the enzyme cyclic GMP-AMP synthase (cGAS) lacking the N-terminal regulatory domain. This design enables constitutive enzymatic activity, catalyzing the production of the second messenger 2′3′-cGAMP upon translation in dendritic cells (DCs), which potently activates the STING pathway independently of self-DNA sensing. As a catalytic adjuvant, it is co-administered with antigen-encoding LNPs to enhance DC maturation, upregulate costimulatory molecules (e.g., CD40, CD80, CD86), MHC proteins, chemokine receptors, and pro-inflammatory cytokines including type I interferons (IFNα, IP-10, RANTES), driving robust antigen-specific CD8+ T cell priming, expansion, and long-term memory formation with Th1-biased responses. Preclinical studies demonstrate superior immunogenicity over standard LNPs in murine models, potentiating antitumor immunity when combined with checkpoint blockade, with applications in cancer vaccines and immunotherapy.