Intracellular Delivery of His-Tagged Genome-Editing Proteins Enabled by Nitrilotriacetic Acid-Containing Lipidoid Nanoparticles
Intracellular Delivery of His-Tagged Genome-Editing Proteins Enabled by Nitrilotriacetic Acid-Containing Lipidoid Nanoparticles
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DOI：
10.1002/adhm.201800996
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发表时间：
2019-03-21
影响因子：
10
通讯作者：
Xu, Qiaobing
中科院分区：
文献类型：
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作者：
Li, Yamin;Li, Alice Chukun;Xu, Qiaobing
基于蛋白质和肽的疗法具有高耐受性和特异性以及低脱靶效应和遗传风险，在过去三十年中引起了极大的关注。在此，报道了一种新型非阳离子类脂质纳米颗粒 (LNP)，用于 His 标记的蛋白质递送。通过将次氮基三乙酸基团与疏水尾部（EC16、O16B 和 O17O）缀合来合成活性类脂质，并在镍离子和辅助脂质（胆固醇、1,2-二油酰-sn-甘油-3-磷酸乙醇胺和1,2-二硬脂酰基-sn-甘油-3-磷酸乙醇胺-N-[甲氧基(聚乙二醇)-2000])。研究表明，新开发的 LNP 能够将各种 His 标签蛋白，包括绿色荧光蛋白 (GFP)、(-30)GFP-Cre 重组酶和 CRISPR/Cas9 核糖核蛋白递送到哺乳动物细胞中。
Protein- and peptide-based therapeutics with high tolerance and specificity along with low off-target effects and genetic risks have attracted tremendous attention over the last three decades. Herein, a new type of noncationic lipidoid nanoparticle (LNP) is reported for His-tagged protein delivery. Active lipidoids are synthesized by conjugating a nitrilotriacetic acid group with hydrophobic tails (EC16, O16B, and O17O) and nanoparticles are formulated in the presence of nickel ions and helper lipids (cholesterol, 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine, and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000]). It is demonstrated that the newly developed LNPs are capable of delivering various His-tagged proteins including green fluorescent protein (GFP), (-30)GFP-Cre recombinase, and CRISPR/Cas9 ribonucleoprotein into mammalian cells.