Cationic lipid-assisted nanoparticles for delivery of mRNA cancer vaccine
Cationic lipid-assisted nanoparticles for delivery of mRNA cancer vaccine
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DOI：
10.1039/c8bm00908b
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发表时间：
2018-11-01
影响因子：
6.6
通讯作者：
Wang, Jun
中科院分区：
文献类型：
--
作者：
Fan, Ya-Nan;Li, Min;Wang, Jun
基于信使RNA的疫苗具有显著的优点，如容易生产，不需要核进入和高安全性，而不需要整合到宿主基因组中，已被证明是细胞毒性免疫系统的有效激活剂。然而，基于mRNA的治疗剂的更广泛应用受到阻碍，因为它们固有地对表达的核酸酶高度脆弱性和直接进入抗原呈递细胞（APC）时的困难。在这里，我们研究了阳离子脂质辅助纳米颗粒（CLAN）的潜力，它形成了一个临床上可翻译的核酸递送系统，作为mRNA疫苗的载体。我们发现，CLAN包裹编码抗原的mRNA在体外和体内都能有效地刺激树突状细胞（DCs）的成熟，并促进抗原特异性T细胞的活化和增殖。静脉内免疫小鼠CLAN含有编码卵清蛋白（OVA）的mRNA引起强烈的OVA特异性T细胞反应，并减缓肿瘤生长的侵略性E中心点G7-OVA淋巴瘤模型。总的来说，CLAN被证明是一个有前途的mRNA疫苗递送平台。
Message RNA-based vaccines with prominent advantages such as facile production, no requirement for nuclear entry and high safety without the need for integration into host genome have been shown to be potent activators of the cytotoxic immune system. However, wider applications of mRNA-based therapeutics have been hindered because of their intrinsically high vulnerability to expressed nucleases and difficulty while entering antigen-presenting cells (APCs) directly. Here, we investigated the potential of cationic lipid-assisted nanoparticles (CLAN), which form a clinically translatable nucleic acid delivery system working as a carrier of an mRNA vaccine. We found that CLAN encapsulating mRNA encoding antigen could effectively stimulate the maturation of dendritic cells (DCs) and promote the activation and proliferation of antigen-specific T cells both in vitro and in vivo. Intravenous immunization of mice with CLAN containing mRNA encoding ovalbumin (OVA) provoked a strong OVA-specific T-cell response and slowed tumor growth in an aggressive E center dot G7-OVA lymphoma model. Collectively, CLAN proved to be a promising platform for mRNA vaccine delivery.