Skip to main page content
U.S. flag
See More

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
Case Reports
. 2025 Jun 12;392(22):2235-2243.
doi: 10.1056/NEJMoa2504747. Epub 2025 May 15.

Patient-Specific In Vivo Gene Editing to Treat a Rare Genetic Disease

Kiran Musunuru  1   2 , Sarah A Grandinette  2 , Xiao Wang  2 , Taylor R Hudson  3 , Kevin Briseno  3 , Anne Marie Berry  2 , Julia L Hacker  2 , Alvin Hsu  4 , Rachel A Silverstein  5 , Logan T Hille  5 , Aysel N Ogul  3 , Nancy A Robinson-Garvin  1 , Juliana C Small  1 , Sarah McCague  1 , Samantha M Burke  1 , Christina M Wright  1 , Sarah Bick  1 , Venkata Indurthi  6 , Shweta Sharma  6 , Michael Jepperson  6 , Christopher A Vakulskas  7 , Michael Collingwood  7 , Katie Keogh  7 , Ashley Jacobi  7 , Morgan Sturgeon  7 , Christian Brommel  7 , Ellen Schmaljohn  7 , Gavin Kurgan  7 , Thomas Osborne  7 , He Zhang  7 , Kyle Kinney  7 , Garrett Rettig  7 , Christopher J Barbosa  8 , Sean C Semple  8 , Ying K Tam  8 , Cathleen Lutz  9 , Lindsey A George  1   2 , Benjamin P Kleinstiver  5 , David R Liu  4 , Kim Ng  1 , Sadik H Kassim  10 , Petros Giannikopoulos  3   11 , Mohamad-Gabriel Alameh  1   2 , Fyodor D Urnov  3 , Rebecca C Ahrens-Nicklas  1   2
Affiliations
Case Reports

Patient-Specific In Vivo Gene Editing to Treat a Rare Genetic Disease

Kiran Musunuru et al. N Engl J Med. .

Abstract

Base editors can correct disease-causing genetic variants. After a neonate had received a diagnosis of severe carbamoyl-phosphate synthetase 1 deficiency, a disease with an estimated 50% mortality in early infancy, we immediately began to develop a customized lipid nanoparticle-delivered base-editing therapy. After regulatory approval had been obtained for the therapy, the patient received two infusions at approximately 7 and 8 months of age. In the 7 weeks after the initial infusion, the patient was able to receive an increased amount of dietary protein and a reduced dose of a nitrogen-scavenger medication to half the starting dose, without unacceptable adverse events and despite viral illnesses. No serious adverse events occurred. Longer follow-up is warranted to assess safety and efficacy. (Funded by the National Institutes of Health and others.).

PubMed Disclaimer

Publication types

MeSH terms

LinkOut - more resources