Fig. 6: NP lipid:mRNA ratio dependent potency correlates with several structural and ionization characteristics of the LNPs. | Communications Biology

Fig. 6: NP lipid:mRNA ratio dependent potency correlates with several structural and ionization characteristics of the LNPs.

From: Ionization and structural properties of mRNA lipid nanoparticles influence expression in intramuscular and intravascular administration

Fig. 6

High dose (200 ng total mRNA) potency of LNPs correlates negatively with a NP lipid:mRNA ratio, b Encapsulation Efficiency and positively with c Diameter, d mRNA copy number, e increase in TNS signal from pH 7.4 to 5 and f increase in zeta potential from pH 7.4 to 5. Reducing the NP lipid:mRNA ratio generates LNPs that are larger, contain more copies of mRNA per LNP (although a lower % of total mRNA) and have larger increases in both surface protonation (TNS in e) and total protonation (ZP in f) when the pH drops from physiological through the endosomal pH range to pH 5. These lower NP LNPs are richer in mRNA vs lipid and have greater protonation in the endosome that may be responsible for increasing their potency.

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