Pancreatic ductal adenocarcinoma remains one of the most lethal malignancies due to dense desmoplastic stroma and lack of druggable targets. Here, we engineer surface-functionalized ionizable lipid nanoparticles encapsulating KRAS-G12D targeted mRNA transcript degraders. In murine xenograft models, targeted LNP delivery induced tumor regression by 78% with negligible systemic hepatotoxicity.
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