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

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…

• CH
  Children's Hospital of Philadelphia
• NI
  National Institutes of Health

  Awards: P01HL142494, R35HL145203, DP2CA281401, U01TR005355
• NH
  National Heart, Lung, and Blood Institute

  Awards: R35HL145203, P01HL142494
• NO
  NIH Office of the Director

  Award: DP2CA281401
• NI
  National Institute of Neurological Disorders and Stroke

  Awards: U19NS132303, U19NS132301
• NC
  National Center for Advancing Translational Sciences

  Award: U01TR005355