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mRNA-LNP-Ery is an erythrocyte-mediated mRNA delivery platform designed for the in vivo generation of chimeric antigen receptor (CAR)-myeloid cells for cancer immunotherapy. The system consists of mRNA-loaded lipid nanoparticles (LNPs) covalently conjugated to erythrocyte membrane proteins in a plug-and-play manner. By leveraging the natural splenic homing capacity of erythrocytes, the platform achieves selective delivery to the spleen, specifically targeting CD11b+ myeloid cells while minimizing hepatic uptake. Once internalized via phagocytosis, the mRNA escapes lysosomal degradation and is translated into CAR proteins (e.g., targeting HER2 or CD19). These engineered myeloid cells adopt a pro-inflammatory, antigen-presenting phenotype, migrate to tumors, and remodel the tumor microenvironment to enhance effector T and NK cell infiltration. The platform has demonstrated therapeutic efficacy in syngeneic tumor models, including immune-cold tumors, at significantly lower doses than conventional mRNA-LNPs.
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