RNA-Based Immunostimulatory Liposomal Spherical Nucleic Acids as Potent TLR7/8 Modulators.
RNA-Based Immunostimulatory Liposomal Spherical Nucleic Acids as Potent TLR7/8 Modulators.
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基于RNA的免疫刺激性脂质体球形核酸作为有效的TLR7/8调节剂。
DOI：
10.1002/smll.201803284
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发表时间：
2018-12
期刊：
影响因子：
--
通讯作者：
Mirkin CA
中科院分区：
文献类型：
--
作者：
Guan C;Chernyak N;Dominguez D;Cole L;Zhang B;Mirkin CA
合成并表征了由Toll样受体(TLRs)7/8选择性RNA组成的免疫刺激球形核酸(IS-LSNAs)。这些结构由脂质体通过疏水的胆固醇部分插入到脂核的壁上，并带有致密的RNA外壳。IS-LSNAs通过在报告细胞系和原代免疫细胞中通过NF-κΒ信号有效地激活TLR7/8，细胞因子的产生和共刺激受体的上调证明了这一点。重要的是，它们优先被浆细胞样树突状细胞摄取，这一观察结果使它们有可能用于免疫治疗。此外，这些结构包含一个核心，可以装载抗原并用于启动T细胞。在这方面，研究表明，负载卵白蛋白多肽的IS-SNAs处理的树突状细胞可以激活OVA特异性CD8+T细胞。除了引入第一个由RNA组成的IS-LSNAs外，这些实验还表明，与对TLR7/8具有选择性的相同序列的游离型或阳离子脂质转染型RNA相比，可以促进抗原特异性T细胞反应。这项工作指向了将由RNA组成的IS-LSNAs作为高效且高度可调的TLR特异性试剂用于开发疫苗和其他需要选择性免疫调节的药物的前景。
Immunostimulatory spherical nucleic acids (IS-LSNAs) comprised of RNA selective for toll-like receptors (TLRs) 7/8 are synthesized and characterized. These structures consist of liposomal cores functionalized with a dense shell of RNA inserted into the wall of the lipid core via hydrophobic cholesterol moieties. IS-LSNAs potently activate TLR7/8 via NF-κΒ signaling in reporter cell lines and in primary immune cells as evidenced by cytokine production and the upregulation of costimulatory receptors. Importantly, they are preferentially taken up by plasmacytoid dendritic cells, an observation that makes them potentially useful for immunotherapy. In addition, these structures contain a core that can be loaded with antigens and used to prime T cells. In this regard, it is shown that dendritic cells treated with IS-SNAs loaded with ovalbumin peptide can prime ova specific CD8+ T cells. In addition to introducing the first IS-LSNAs consisting of RNA, these experiments show that one can facilitate an antigen-specific T cell response greater than that of free or cationic lipid-transfected RNA of the same sequence selective for TLR7/8. This work points toward the promise of using IS-LSNAs comprised of RNA as potent and highly tunable TLR-specific agents for the development of vaccines and other pharmaceuticals that require selective immunomodulation.
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影响因子：
11.2
作者：
Chen S;Wang L;Fan J;Ye C;Dominguez D;Zhang Y;Curiel TJ;Fang D;Kuzel TM;Zhang B
通讯作者：
Zhang B
影响因子：
4.4
作者：
Hornung, V;Rothenfusser, S;Hartmann, G
通讯作者：
Hartmann, G
影响因子：
4.4
作者：
Bekeredjian-Ding, IB;Wagner, M;Hartmann, G
通讯作者：
Hartmann, G
DOI：
10.1073/pnas.1305804110
发表时间：
2013-05-07
影响因子：
11.1
作者：
Choi, Chung Hang J.;Hao, Liangliang;Mirkin, Chad A.
通讯作者：
Mirkin, Chad A.
影响因子：
15
作者：
Cutler, Joshua I.;Auyeung, Evelyn;Mirkin, Chad A.
通讯作者：
Mirkin, Chad A.