Toll-like receptor 2 agonist Pam3CSK4 enhances lipid nanoparticle uptake and enhanced green fluorescent protein mRNA translation in dendritic cells

Document Type

Poster

Date of Original Version

3-27-2026

Abstract

Messenger ribonucleic acid (mRNA) vaccines require translation in host cells to elicit antigen-specific immune responses. Dendritic cells (DCs) are known to be professional antigen-presenting cells (APCs), responsible for bridging adaptive immunity. Thus, enhancing mRNA translation in DCs has important implications to enhance mRNA vaccine efficacy. This study found toll-like receptor 2 (TLR2) agonist Pam3CSK4 was highly potent to enhance lipid nanoparticle (LNP) encapsulated enhanced green fluorescent protein (EGFP) mRNA translation in murine bone marrow-derived DCs (BMDCs) at concentrations as low as 1 ng/mL. We further found Pam3CSK4 could enhance DiD-encapsulated LNP uptake with high dependence on TLR2. Pre-incublation of BMDCs with EGFP mRNA for 2 hours followed by washing away EGFP mRNA in the medium and overnight incubation with Pam3CSK4 found Pam3CSK4 could still enhance EGFP expression. Thus, our data support that Pam3CSK4 could simultaneously enhance LNP uptake and EGFP mRNA translation in BMDCs.

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