用于肺部mRNA递送和基因组编辑的纳米颗粒的组合设计。
Combinatorial design of nanoparticles for pulmonary mRNA delivery and genome editing.
作者信息
Li Bowen, Manan Rajith Singh, Liang Shun-Qing, Gordon Akiva, Jiang Allen, Varley Andrew, Gao Guangping, Langer Robert, Xue Wen, Anderson Daniel
机构信息
David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
出版信息
Nat Biotechnol. 2023 Oct;41(10):1410-1415. doi: 10.1038/s41587-023-01679-x. Epub 2023 Mar 30.
Abstract
The expanding applications of nonviral genomic medicines in the lung remain restricted by delivery challenges. Here, leveraging a high-throughput platform, we synthesize and screen a combinatorial library of biodegradable ionizable lipids to build inhalable delivery vehicles for messenger RNA and CRISPR-Cas9 gene editors. Lead lipid nanoparticles are amenable for repeated intratracheal dosing and could achieve efficient gene editing in lung epithelium, providing avenues for gene therapy of congenital lung diseases.
摘要
非病毒基因组药物在肺部的应用拓展仍受递送难题的限制。在此，我们利用一个高通量平台，合成并筛选了一个可生物降解的离子izable脂质组合文库，以构建用于信使核糖核酸和CRISPR-Cas9基因编辑器的可吸入递送载体。主要的脂质纳米颗粒适合重复气管内给药，并能在肺上皮细胞中实现高效基因编辑，为先天性肺部疾病的基因治疗提供了途径。
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