Lipid Nanoparticle Formulations for Enhanced Co-delivery of siRNA and mRNA

Co-formulation of siRNA and mRNA in the same nanoparticle enhanced both therapies, achieving up to 87% gene silencing in mice.

• The combination of siRNA and mRNA in a single lipidoid nanoparticle formulation improved the efficacy of both agents in vitro and in vivo.
• Co-formulated nanoparticles achieved Factor VII gene silencing of 87% with an siRNA dose of 0.03 mg/kg, compared to 44% with siRNA alone.
• A dose of 0.5 mg/kg mRNA co-formulated with siRNA resulted in three times the luciferase protein expression compared to mRNA delivery without siRNA.
• Substituting helper RNA with the negatively charged polymer polystyrenesulfonate (PSS) maintained efficacy while using 2-3-fold less RNA.
• LNPs containing PSS achieved 50% Factor VII silencing at siRNA doses of 0.01 mg/kg, demonstrating similar performance to standard formulations.

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