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.

Intellia Therapeutics 的基于 CRISPR-Cas9 的基因编辑疗法可将遗传性血管性水肿 (HAE) 患者每月的肿胀发作减少 95%。一项小型一期试验的结果于二月份发表在《新英格兰医学杂志》上。HAE 是一种罕见的遗传性疾病，其特征是反复发作的皮下和粘膜下肿胀，可能危及生命。激肽释放酶是一种在疾病中升高的酶，与补体系统相互作用，导致其过度激活。Intellia 的基于 CRISPR 的基因编辑疗法 NTLA-2002 靶向并灭活KLKB1基因，该基因编码激肽释放酶的前体。该公司的非病毒平台使用脂质纳米粒子，将KLKB1基因特异的引导 RNA 和编码 Cas9 酶的 mRNA 输送到肝脏，在那里进行精确编辑。

该试验涉及 10 名 HAE 患者，他们接受了三种不同剂量的 NTLA-2002 单次注射。对患者进行了 16 周的随访，尽管反应并不依赖于剂量，但 NTLA-2002 将患者血浆中的激肽释放酶蛋白降低了 67-84%，每月发作平均减少了 95%。不良事件包括输液相关反应和疲劳。第二阶段试验的安慰剂对照部分正在进行中。