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

2025/05/15 by Kiran Musunuru, Sarah Grandinette, Xiao Wang +42 · 2 voices · 14 citations
Biochemistry, Genetics and Molecular Biology · #Animal Genetics and Reproduction #CRISPR and Genetic Engineering #Pluripotent Stem Cells Research

paper · doi:10.1056/nejmoa2504747

openalex publication_date 2025/05/15 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/31

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.).

Citations

• A Programmable Dual-RNA–Guided DNA Endonuclease in Adaptive Bacterial Immunity

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Discussions

• (2) Publicação do estudo: Musunuru et al. (2025). Patient-Specific In Vivo Gene Editing to Treat a Rare Genetic Disease. NEJM. doi.org/10.1056/NEJM... Referência adicional: www.nature.com/articles/d [bsky, 3 points, 0 comments]
• The article discuss to follow along Musunuru, K. . . . Ahrens-Nicklas, R. C. et al. -Specific In Vivo Gene Editing to Treat a Rare Genetic Disease. N Engl J Med 2025. doi.org/10.1056/nejm.... [bsky, 0 points, 0 comments]

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• A hit for base editing: treatment of developmental epilepsy in a mouse model