Hepatic-targeted RNA interference provides robust and persistent knockdown of alpha-1 antitrypsin levels in ZZ patients
Background & Aims Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder causing
pulmonary and liver disease. The PiZ mutation in AAT (SERPINA1) results in mis-folded AAT
protein (Z-AAT) accumulating in hepatocytes, leading to fibrosis and cirrhosis. RNAi-based
therapeutics silencing production of hepatic Z-AAT might benefit patients with AATD-
associated liver disease. This study evaluated an RNAi therapeutic to silence production of
AAT. Methods Part A of this double-blind first-in-human study randomized 54 healthy …
pulmonary and liver disease. The PiZ mutation in AAT (SERPINA1) results in mis-folded AAT
protein (Z-AAT) accumulating in hepatocytes, leading to fibrosis and cirrhosis. RNAi-based
therapeutics silencing production of hepatic Z-AAT might benefit patients with AATD-
associated liver disease. This study evaluated an RNAi therapeutic to silence production of
AAT. Methods Part A of this double-blind first-in-human study randomized 54 healthy …