How drug form and timing affect inflammation and gene activity of lipid-based JAK-inhibitor and corticosteroid treatments

Co-formulation of peficitinib with saRNA-lipid nanoparticles may exacerbate endosomal damage signaling.

• saRNA-lipid nanoparticle therapeutics allow prolonged protein expression at lower doses than traditional mRNA systems.
• Pronounced innate immune activation from saRNA replication intermediates and LNP components limits clinical translation.
• Co-formulation of peficitinib increased endosomal damage signaling and hindered saRNA replication and expression.
• Independent delivery of peficitinib delayed immune responses, preserving saRNA replication and expression.
• Formulation strategy and timing, rather than drug identity alone, significantly affect the balance between inflammation control and therapeutic efficacy.

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