S. C. Alexander et al.
Transthyretin amyloidosis (ATTR) is a progressive disease caused by accumulation of amyloid deposits of misfolded transthyretin (TTR) protein in multiple tissues including the heart, nerves and gastrointestinal tract. Reduction of TTR monomer via stabilization of circulating tetramer and silencing of TTR gene expression in hepatocytes of ATTR patients have emerged as successful therapeutic strategies for chronically-administered medicines. As such, specific disruption (or knockout) of the TTR gene in hepatocytes using the CRISPR/Cas9 gene editing system is a potentially attractive next- generation treatment for ATTR, which may durably reduce the expression of TTR without the need for chronic therapy.
… NTLA-2001 achieves significant knockdown of the TTR protein by editing the TTR gene across multiple species, including mouse and NHP
Demonstrated the potential of LNP-delivered in vivo CRISPR/Cas9 gene editing; suggests that future therapies based on this platform may enable next-generation, curative treatment paradigms for chronic genetic diseases such as ATTR