DNA条形码
信使核糖核酸
吞吐量
纳米颗粒
计算生物学
阳离子聚合
生物
细胞生物学
化学
纳米技术
基因
计算机科学
遗传学
材料科学
进化生物学
电信
有机化学
无线
作者
Lulu Xue,Alex G. Hamilton,Guomao Zhao,Zhang Xiao,Rakan El‐Mayta,Xue Han,Ningqiang Gong,Xinhong Xiong,Junchao Xu,Christian G. Figueroa‐Espada,Sarah Shepherd,Alvin J. Mukalel,Mohamad-Gabriel Alameh,Jiaxi Cui,Karin Wang,Andrew E. Vaughan,Drew Weissman,Michael J. Mitchell
标识
DOI:10.1038/s41467-024-45422-9
摘要
Abstract Lipid nanoparticles for delivering mRNA therapeutics hold immense promise for the treatment of a wide range of lung-associated diseases. However, the lack of effective methodologies capable of identifying the pulmonary delivery profile of chemically distinct lipid libraries poses a significant obstacle to the advancement of mRNA therapeutics. Here we report the implementation of a barcoded high-throughput screening system as a means to identify the lung-targeting efficacy of cationic, degradable lipid-like materials. We combinatorially synthesize 180 cationic, degradable lipids which are initially screened in vitro. We then use barcoding technology to quantify how the selected 96 distinct lipid nanoparticles deliver DNA barcodes in vivo. The top-performing nanoparticle formulation delivering Cas9-based genetic editors exhibits therapeutic potential for antiangiogenic cancer therapy within a lung tumor model in female mice. These data demonstrate that employing high-throughput barcoding technology as a screening tool for identifying nanoparticles with lung tropism holds potential for the development of next-generation extrahepatic delivery platforms.
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