Figure 5.
Ligand-Conjugated Antisense Technology
GalNAc-conjugate moiety delivers the ASO to the hepatocytes where hepatic AGT is made. Targeting the top of RAAS pathway by reducing liver-derived AGT is a novel mechanism for RAAS inhibition. This GalNAc conjugation will minimize renal AGT reduction and thereby potentially provide a better safety profile than other RAAS inhibitors. AGT = angiotensinogen; ASGR = asialoglycoprotein receptor; ASO = antisense oligonucleotide; GaINAc3 = triantennary N-acetyl galactosamine; mRNA = messenger RNA; RAAS = renin-angiotensin-aldosterone system.