Postdoctoral Associate MIT Cambridge, Massachusetts, United States
Introduction: Oral and buccal delivery of mRNA could transform nucleic acid therapy by enabling noninvasive, repeatable dosing, but remains limited by gastrointestinal degradation, poor epithelial uptake, and endosomal sequestration of lipid nanoparticles.1, 2, 3 We investigated that rationally selected small‑molecule modulators, acting on endocytosis and endolysosomal escape, could synergize with optimized lipid nanoparticles to enhance local mRNA delivery to the cheek epithelium in preclinical models.
Learning Objectives:
describe key barriers to oral and buccal mRNA delivery with lipid nanoparticles.
explain how small‑molecule modulators can enhance endocytic uptake and endosomal escape of mRNA-LNP.
discuss how formulation parameters and mechanism‑guided design inform development of oral RNA therapeutics
