清脆的
囊性纤维化
囊性纤维化跨膜传导调节器
基因组编辑
遗传增强
生物
Cas9
计算生物学
无义突变
基因
细胞生物学
遗传学
突变
错义突变
作者
Tuo Wei,Yehui Sun,Qiang Cheng,Sumanta Chatterjee,Zachary Traylor,Lindsay T. Johnson,Melissa Coquelin,Jialu Wang,Michael J. Torres,Xizhen Lian,Xu Wang,Yufen Xiao,Craig A. Hodges,Daniel J. Siegwart
标识
DOI:10.1038/s41467-023-42948-2
摘要
Approximately 10% of Cystic Fibrosis (CF) patients, particularly those with CF transmembrane conductance regulator (CFTR) gene nonsense mutations, lack effective treatments. The potential of gene correction therapy through delivery of the CRISPR/Cas system to CF-relevant organs/cells is hindered by the lack of efficient genome editor delivery carriers. Herein, we report improved Lung Selective Organ Targeting Lipid Nanoparticles (SORT LNPs) for efficient delivery of Cas9 mRNA, sgRNA, and donor ssDNA templates, enabling precise homology-directed repair-mediated gene correction in CF models. Optimized Lung SORT LNPs deliver mRNA to lung basal cells in Ai9 reporter mice. SORT LNP treatment successfully corrected the CFTR mutations in homozygous G542X mice and in patient-derived human bronchial epithelial cells with homozygous F508del mutations, leading to the restoration of CFTR protein expression and chloride transport function. This proof-of-concept study will contribute to accelerating the clinical development of mRNA LNPs for CF treatment through CRISPR/Cas gene correction.
科研通智能强力驱动
Strongly Powered by AbleSci AI