VEGF-A Expression Saturation in Heart

Example 11

VEGF-A Protein Expression after Modified RNA Injection to the Heart with Citrate Saline Buffer is Saturable and has Similar Pharmacokinetics Across Multiple Species

To compare VEGF-A protein production, 150 μg of VEGF-A modified RNA in a citrate saline buffer and 100 μg of VEGF-A modified RNA using RNAiMax (a lipid-based formulation) as the delivery carrier were injected into a rat heart. After 24 hours, VEGF-A protein levels in the rats with the citrate saline buffer (NTB) was at a comparable level to rats injected with RNAiMax and the pharmacokinetic profile were similar (FIG. 12A). The protein expression was dose limited and saturable, which was seen across species (FIG. 12B). With a ten-fold increase in dose, there was only a 1.6-fold increase in the area under the curve (FIG. 12C).