近日，美国费城儿童医院Rebecca C. Ahrens-Nicklas团队研究了患者特异性体内基因编辑治疗罕见遗传疾病。这一研究成果于2025年5月15日发表在《新英格兰医学杂志》上。

碱基编辑器可以纠正致病基因变异。在一名新生儿被诊断为严重的氨甲酰磷酸合成酶1缺乏症（一种在婴儿早期估计死亡率为50%的疾病）后，研究组立即开始开发一种定制的脂质纳米粒子递送的碱基编辑疗法。在获得治疗的监管批准后，患者在大约7个月和8个月大时接受了两次输注。

在初次输注后的7周内，患者能够接受更多的膳食蛋白质，并将氮清除剂药物的剂量减少到起始剂量的一半，没有出现不可接受的不良事件，尽管存在病毒性疾病。未发生严重不良事件。需要更长的随访时间来评估安全性和有效性。

附：英文原文

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

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

Issue&Volume: 2025-05-15

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.

DOI: NJ202505150000002

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2504747