In Vivo CRISPR Therapy is One Step Closer to the Clinic

By Bio-IT World News Staff 

July 23, 2026 | A one-time, in vivo CRISPR gene-editing therapy from Intellia Therapeutics could become the first approved treatment of its kind for patients with hereditary angioedema. The experimental therapy, lonvoguran ziclumeran (lonvo-z), reduced hereditary angioedema (HAE) attacks by 87% in a phase 3 trial and could be submitted for regulatory review in the United States and Europe within the next year, according to Danny Cohn, M.D., Ph.D., head of the hereditary angioedema clinic at Amsterdam University Medical Center and a principal investigator of the HAELO study. 

Published in The New England Journal of Medicine (DOI: 10.1056/NEJMoa2600931), the randomized, placebo-controlled trial is the first phase 3 evaluation of an in vivo CRISPR therapy, in which gene-editing components are delivered directly into the body to modify cells in place. Unlike ex vivo approaches that require cells to be removed, edited, and reinfused, lonvo-z targets liver cells to disrupt the KLKB1 gene, halting production of plasma kallikrein and reducing the bradykinin signaling that drives HAE attacks. 

The study enrolled 80 patients with hereditary angioedema caused by C1 inhibitor deficiency, randomizing participants 2:1 to receive lonvo-z or placebo. About 62% of treated patients remained attack-free without maintenance therapy, compared with 11% in the placebo group. Use of on-demand medications declined by 89%, while moderate-to-severe attacks fell by 91%. 

Cohn noted that efficacy may ultimately increase closer to 100%, especially now that the study has been unblinded. Previous phase 1 and 2 studies showed nearly all patients receiving the therapeutic dose became attack-free. Because no validated biomarker definitively distinguishes hereditary angioedema attacks from nonspecific symptoms, some mild events may have been overreported during the blinded phase. 

For the broader gene-editing field, the study represents a key validation of systemic, in vivo CRISPR delivery and can possibly go beyond hereditary angioedema. Cohn noted that more than 100 diseases were already under investigation using CRISPR-based approaches several years ago, with programs spanning both in vivo and ex vivo editing. At Amsterdam University Medical Center, investigators are also evaluating in vivo CRISPR to lower LDL cholesterol in patients with coronary artery disease. 

To read the full story by Deborah Borfitz, visit Clinical Research News.