Impact of Serum Proteins on the Uptake and RNAi Activity of GalNAc-Conjugated siRNAs.

ABSTRACT: Serum protein interactions are evaluated during the drug development process since they determine the free drug concentration in blood and thereby can influence the drug's pharmacokinetic and pharmacodynamic properties. While the impact of serum proteins on the disposition of small molecules is well understood, it is not yet well characterized for a new modality, RNA interference therapeutics. When administered systemically, small interfering RNAs (siRNAs) conjugated to the N-acetylgalactosamine (GalNAc) ligand bind to proteins present in circulation. However, it is not known if these protein interactions may impact the GalNAc-conjugated siRNA uptake into hepatocytes mediated through the asialoglycoprotein receptor (ASGPR) and thereby influence the activity of GalNAc-conjugat

SUBMITTER: Agarwal S 

PROVIDER: S-EPMC8377513 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature