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Abstract
Mannose-cholesterol LNPs achieve 9.9-fold greater brain accumulation than non-targeted formulations in healthy mice.
- GLUT1 is a potential target for delivering mRNA to brain tumors due to its abundance on brain blood vessels and overexpression in glioblastoma.
- High ligand densities on LNPs are necessary for effective GLUT1 engagement but are difficult to achieve with conventional methods.
- Mannose-cholesterol conjugation allows for ~30 mol% surface ligand density without compromising mRNA encapsulation.
- Functional delivery of Cre mRNA using MC_LNPs shows expression in neurons and astrocytes in Ai14 reporter mice.
- In glioblastoma models, mRNA-loaded MC_LNPs reduce tumor burden by 6-fold and extend median survival from 33 to 49 days.
Simplified
mRNA Technology