Using Tissue-Specific Silencing of Synthetic mRNAs to Identify Vaccination-Active Tissues and Reduce Immune Response to Cas9

Muscle and spleen are identified as the most immunologically competent tissues for robust immune priming in mRNA/LNP vaccine models.

• The study investigates how specific organs influence immune responses triggered by mRNA lipid nanoparticle (LNP) vaccines.
• Engineered mRNAs with de-targeting elements allow selective silencing of antigen expression in certain tissues.
• A causal link between translation sites and immune outputs is established through this selective silencing approach.
• The findings suggest a framework for designing mRNA/LNP formulations that enhance targeting precision and reduce side effects.
• This strategy can also be applied to genome editing, potentially lowering the immunogenicity and toxicity of mRNA-Cas9 treatments.

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