Hepatocyte-like cell platforms for in vitro evaluation of antisense drugs in familial amyloidosis using stem cell technology

Familial amyloidosis (ATTR) is a neurodegenerative disease caused by mutations of the transthyretin (TTR) gene that is mostly (> 95%) expressed by liver. Currently, more than 100 TTR mutations have been discovered in patients with ATTR, with different clinical manifestation. Drug therapy of ATTR is partially possible on a protein level. However, a full silencing of the mutated TTR gene would enormously increase therapeutic outcome. Antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs) are the most commonly used gene-silencing strategies. These artificial nucleotides bind complementary to the targ…