Self-Amplifying Replicon RNA Delivery to Dendritic Cells by Cationic Lipids.
Self-Amplifying Replicon RNA Delivery to Dendritic Cells by Cationic Lipids.
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DOI：
10.1016/j.omtn.2018.04.019
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发表时间：
2018-09-07
期刊：
影响因子：
--
通讯作者：
McCullough KC
中科院分区：
文献类型：
--
作者：
Englezou PC;Sapet C;Démoulins T;Milona P;Ebensen T;Schulze K;Guzman CA;Poulhes F;Zelphati O;Ruggli N;McCullough KC
在过去的二十年中，RNA技术的进步已经导致构建了具有复制能力的RNA，称为复制子，RepRNA或自扩增mRNA，具有很高的疫苗应用潜力。胞质递送对于它们的翻译和自我复制是必不可少的，而没有感染性后代的产生，提供高水平的抗原表达以诱导体液和细胞免疫。基于合成纳米颗粒的递送载体既可以保护RNA分子，又可以促进树突状细胞的靶向，这对免疫防御的发展至关重要。用编码甲型流感病毒核蛋白基因的猪瘟病毒产生的RepRNA评估了几种阳离子脂质。RNA的非致细胞病变性质允许靶向树突细胞而不破坏细胞-这对于延长抗原产生和呈递是重要的。某些脂质在递送和促进RepRNA翻译方面比其他脂质更有效。选择特定的脂质向树突细胞提供递送，导致翻译，表明递送效率不能保证翻译。通过诱导针对编码的流感病毒抗原的免疫应答，在体内再现了体外观察到的翻译。阳离子脂质介导的递送显示出促进RepRNA疫苗递送至树突细胞的潜力，特别是当与另外的递送元件组合时。
Advances in RNA technology during the past two decades have led to the construction of replication-competent RNA, termed replicons, RepRNA, or self-amplifying mRNA, with high potential for vaccine applications. Cytosolic delivery is essential for their translation and self-replication, without infectious progeny generation, providing high levels of antigen expression for inducing humoral and cellular immunity. Synthetic nanoparticle-based delivery vehicles can both protect the RNA molecules and facilitate targeting of dendritic cells—critical for immune defense development. Several cationic lipids were assessed, with RepRNA generated from classical swine fever virus encoding nucleoprotein genes of influenza A virus. The non-cytopathogenic nature of the RNA allowed targeting to dendritic cells without destroying the cells—important for prolonged antigen production and presentation. Certain lipids were more effective at delivery and at promoting translation of RepRNA than others. Selection of particular lipids provided delivery to dendritic cells that resulted in translation, demonstrating that delivery efficiency could not guarantee translation. The observed translation in vitro was reproduced in vivo by inducing immune responses against the encoded influenza virus antigens. Cationic lipid-mediated delivery shows potential for promoting RepRNA vaccine delivery to dendritic cells, particularly when combined with additional delivery elements.
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