In vivo correction of cystic fibrosis mediated by PNA nanoparticles.
In vivo correction of cystic fibrosis mediated by PNA nanoparticles.
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DOI：
10.1126/sciadv.abo0522
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发表时间：
2022-10-07
期刊：
影响因子：
13.6
通讯作者：
中科院分区：
文献类型：
--
作者：
囊性纤维化是由囊性纤维化跨膜电导调节基因突变引起的。我们试图通过生物相容的聚合物纳米颗粒介导的系统递送多肽核酸基因编辑技术来纠正F508del CF突变引起的多器官功能障碍。我们证实了在气液界面生长的F508del小鼠的原代鼻腔上皮细胞的体外表型和基因修饰，以及静脉注射后在F508del小鼠体内的表型和基因修饰。通过原位电位差和Ussing小室分析，体内治疗导致上皮细胞CFTR功能的部分增加，并纠正了呼吸道和胃肠道组织的CFTR，没有超过背景的偏离靶点的影响。我们的研究表明，系统性基因编辑是可能的，更具体地说，静脉注射旨在纠正导致CF的突变的PNA NPs是改善多个受影响器官中的CF的可行选择。包裹PNA基因编辑剂的聚合物纳米颗粒在体内纠正多个器官中的囊性纤维化突变。
Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. We sought to correct the multiple organ dysfunction of the F508del CF-causing mutation using systemic delivery of peptide nucleic acid gene editing technology mediated by biocompatible polymeric nanoparticles. We confirmed phenotypic and genotypic modification in vitro in primary nasal epithelial cells from F508del mice grown at air-liquid interface and in vivo in F508del mice following intravenous delivery. In vivo treatment resulted in a partial gain of CFTR function in epithelia as measured by in situ potential differences and Ussing chamber assays and correction of CFTR in both airway and GI tissues with no off-target effects above background. Our studies demonstrate that systemic gene editing is possible, and more specifically that intravenous delivery of PNA NPs designed to correct CF-causing mutations is a viable option to ameliorate CF in multiple affected organs. Polymeric nanoparticles encapsulating PNA gene editing agents correct cystic fibrosis mutations in multiple organs in vivo.
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影响因子：
21.3
作者：
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56.9
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12.3
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