Rena Baek, Kimberly Coughlan, Lei Jiang, Min Liang, Lei Ci, Harkewal Singh, Hannah Zhang, Neeraj Kaushal, Ivana Liric Rajlic, Linh Van, Rain Dimen, Alexander Cavedon, Ling Yin, Lisa Rice, Andrea Frassetto, Lin Guey, Patrick Finn, Paolo G V Martini
Messenger RNA (mRNA) therapeutics delivered via lipid nanoparticles hold the potential to treat metabolic diseases caused by protein deficiency, including propionic acidemia (PA), methylmalonic acidemia (MMA), and phenylketonuria (PKU). Herein we report results from multiple independent preclinical studies of mRNA-3927 (an investigational treatment for PA), mRNA-3705 (an investigational treatment for MMA), and mRNA-3210 (an investigational treatment for PKU) in murine models of each disease. All 3 mRNA therapeutics exhibited pharmacokinetic/pharmacodynamic (PK/PD) responses in their respective murine model by driving mRNA, protein, and/or protein activity responses, as well as by decreasing levels of the relevant biomarker(s) when compared to control-treated animals...
May 7, 2024: Nature Communications