Bioconjugate chemistry

Lipid Nanoparticles Coated with Polymers for Targeted mRNA Delivery Using Nanobody Attachment

Updated

Abstract

9G8-attached PMSEA mRNA-LNPs showed significantly enhanced cell association and transfection efficiency with an EGFR-positive cell line.

  • Current immunotherapeutic mRNA approaches lack site- and immune-cell-specific delivery, leading to off-target immune responses.
  • Commercial lipid nanoparticle formulations tend to accumulate significantly in the liver during clearance.
  • Bioconjugation methods were explored to attach targeting antibodies to polymer-functionalized mRNA lipid nanoparticles.
  • The incorporation of cyclooctene functionality in PMSEA-DSPE allowed for effective conjugation to the tetrazine-functionalized nanobody 9G8.
  • Active targeting through 9G8 conjugation could enhance mRNA-LNP platform efficacy.

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