Preclinical Development – Biomolecular
2019 PharmSci 360
GalNAc-conjugated siRNAs are synthetic, chemically modified, double stranded small interfering RNAs conjugated to a triantennary N-acetylgalactosamine ligand to facilitate preferential delivery to the liver. Presentation highlights the unique pre-clinical ADME and pharmacokinetic properties of GalNAc-siRNAs. In addition, radiolabeled QWBA and metabolite profiling data are included to provide a quantitative illustration of in vivo disposition of GalNAc-siRNAs in preclinical animal species. Comprehensive in vitro drug-drug interaction involving drug metabolizing enzymes (CYPs) and transporters is also summarized.