Acuitas: (noun) insight, perception, sharpness.


LNP Access to Cells After Systemic Administration


Acuitas scientists, in collaboration with other researchers, have established the mechanism whereby certain LNP carriers can provide highly efficient delivery to hepatocytes in the liver (Akinc et al., Mol Ther. 2010). After intravenous administration, the PEG-lipid component that shields the surface of our LNP exchanges off. This allows binding of the plasma protein ApoE to the exposed neutral LNP surface. In the liver, the LNP with bound ApoE passes out of the blood vessels through holes (“fenestrations”) and accesses the interstitial space. The bound ApoE is then recognized by receptors on the surface of hepatocytes resulting in an uptake of the LNP into endosomes.

As the endosome “matures,” its interior becomes more acidic causing the cationic lipid within the LNP to become positively charged. The charged LNP then interacts with negatively charged lipids within the endosome membrane, resulting in a rupture of the LNP and a delivery of the mRNA payload into the cell cytoplasm.

This cellular uptake process is also believed to be the route of entry into other cell types after local administration (e.g.: for mRNA-LNP vaccines).