Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2026 Mar 26;394(12):1195-1203.
doi: 10.1056/NEJMoa2509807. Epub 2025 Dec 7.

Prime Editing for p47phox-Deficient Chronic Granulomatous Disease

Jennifer L Gori  1 , Elie Haddad  2   3 , Haydar Frangoul  4 , Donald B Kohn  5 , Emma C Morris  6 , Bradley N Martin  1 , Briana A Deary  1 , McKinley Nickerson  1 , Rebecca L Scholz  1 , Isabel Fernandez  2   3 , Karine Leveille  2   3 , Suk See De Ravin  7 , Elizabeth M Kang  7 , Marie Pierzynski  7 , Tyra Estwick  7 , Patricia Littel  7 , Douglas B Kuhns  8 , Debra A Long Priel  8 , Pierre Teira  2 , Stuart Turvey  9 , Jordyn Arnold  5 , Misty D Evans  4 , Meghann McManus  4 , Ben Carpenter  10 , David P Waterman  1 , Andrew V Anzalone  1 , Alexandria Petrusich  1 , Christa E Osuna  1 , Tiernan T O'Malley  1 , Jacob Stewart-Ornstein  1 , Jack M Heath  1 , Barrett J Nehilla  1 , Mohammed Asmal  1 , Harry L Malech  7
Affiliations
Free article
Clinical Trial

Prime Editing for p47phox-Deficient Chronic Granulomatous Disease

Jennifer L Gori et al. N Engl J Med. .
Free article

Abstract

Chronic granulomatous disease (CGD) is a severe monogenic immunodeficiency caused by damaging variants in genes required for microbicidal NADPH oxidase activity. Autosomal recessive p47phox-deficient CGD (p47-CGD) is predominantly caused by a two-nucleotide deletion in exon 2 (delGT) of NCF1. We developed PM359, an autologous CD34+ hematopoietic stem-cell therapy in which prime editing is used to correct delGT. Two participants received PM359 after myeloid conditioning with busulfan: neutrophils and platelets engrafted promptly in both patients. Adverse events were consistent with myeloid conditioning with busulfan. NADPH oxidase activity was observed in neutrophils within 1 month and was maintained for 6 months and 4 months as of the last follow-up visit in Participants 1 and 2, respectively. These results support further investigation of prime editing of CD34+ cells to treat p47-CGD. (Funded by Prime Medicine; ClinicalTrials.gov number, NCT06559176.).

PubMed Disclaimer

Publication types

MeSH terms

Associated data