Gene Editing — A Cure for Transthyretin Amyloidosis?

This editorial explores the therapeutic potential of in vivo CRISPR-Cas9 gene editing for transthyretin amyloidosis (ATTR), a progressive multisystemic disease caused by misfolded transthyretin protein accumulating in nerves and heart. The author reflects on the severe clinical burden of hereditary ATTR and reviews emerging therapies, including stabilizers (e.g., tafamidis), silencers (e.g., patisiran), and antisense oligonucleotides. The piece centers on NTLA-2001, a lipid nanoparticle–based CRISPR therapy that permanently reduces hepatic transthyretin production after a single infusion. Early results in six patients showed dose-dependent reductions in serum TTR and no serious safety signals. While promising, the editorial urges caution due to limited follow-up and sample size. It concludes with optimism about advancing ATTR treatment through collaboration among research, regulatory, and patient communities.

This editorial explores the therapeutic potential of in vivo CRISPR-Cas9 gene editing for transthyretin amyloidosis (ATTR), a progressive multisystemic disease caused by misfolded transthyretin protein accumulating in nerves and heart. The author reflects on the severe clinical burden of hereditary ATTR and reviews emerging therapies, including stabilizers (e.g., tafamidis), silencers (e.g., patisiran), and antisense oligonucleotides. The piece centers on NTLA-2001, a lipid nanoparticle–based CRISPR therapy that permanently reduces hepatic transthyretin production after a single infusion. Early results in six patients showed dose-dependent reductions in serum TTR and no serious safety signals. While promising, the editorial urges caution due to limited follow-up and sample size. It concludes with optimism about advancing ATTR treatment through collaboration among research, regulatory, and patient communities.