A CRISPR–Cas9-based gene editing therapy from Intellia Therapeutics reduced monthly swelling attacks by 95% in people with hereditary angioedema (HAE). The results from a small phase 1 trial were published in the New England Journal of Medicine in February. HAE is a rare genetic disorder characterized by recurrent bouts of subcutaneous and submucosal swelling that can be life threatening. Kallikrein, an enzyme that is elevated in the disease, interacts with the complement system, leading to its overactivation. Intellia’s CRISPR-based gene editing therapy NTLA-2002 targets and inactivates the KLKB1 gene, which encodes the precursor to the kallikrein enzyme. Using lipid nanoparticles, the company’s non-viral platform delivers a guide RNA specific for the KLKB1 gene and mRNA encoding the Cas9 enzyme to the liver, where they carry out the precision editing.

The trial involved ten people with HAE who received a single shot of NTLA-2002 in three different doses. The patients were followed for 16 weeks and, although the responses were not dose dependent, NTLA-2002 reduced kallikrein protein in patients’ plasma by 67–84% and monthly attacks diminished by 95% on average. Adverse events included infusion-related reactions and fatigue. The phase 2 placebo-controlled portion of the trial is ongoing.