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