Scaffold-mediated delivery for non-viral mRNA vaccines.
Scaffold-mediated delivery for non-viral mRNA vaccines.
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非病毒 mRNA 疫苗的支架介导递送。
DOI：
10.1038/s41434-018-0040-9
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发表时间：
2018-12
期刊：
影响因子：
5.1
通讯作者：
Bryers JD
中科院分区：
文献类型：
--
作者：
Chen R;Zhang H;Yan J;Bryers JD
mRNA越来越被认为是基因疫苗中pDNA的有前途的替代品。直到最近，由于癌症免疫疗法的需要，生物材料/基因递送社区才开始开发用于免疫调节的新生物材料策略。在这里，我们报告了一种新的方法，使用可植入的多孔支架作为一个本地的基因传递仓库，以提高mRNA疫苗免疫在体外和体内相比，传统的弹丸注射。我们首先评估了用两种脂质（Lipofectamine Messenger MAX™ LM-MM和Stemfect™ SF）和两种阳离子聚合物（体内-jetPEI ™，聚（β-氨基酯））作为基因载体浓缩和电荷中和的单链mRNA的转染效率。由于SF表现出最高的体外转染和细胞活力，因此选择其用于随后的多孔聚合物支架加载试验。用DC2.4细胞系也观察到SF：mRNA纳米颗粒加载的聚（甲基丙烯酸2-羟乙酯）（pHEMA）支架的体外转染增强。与推注相比，SF：mRNA纳米颗粒负载的pHEMA支架在体内也证明了持续局部释放和局部转基因表达的改善。我们的研究结果表明，mRNA聚合物负载的支架可能是一个上级替代重复团注免疫或离体转染细胞免疫疗法。
mRNA is increasingly being recognized as a promising alternative to pDNA in gene vaccinations. Only recently, owing to the needs of cancer immunotherapies, has the biomaterials/gene delivery community begun to develop new biomaterial strategies for immunomodulation. Here, we report a novel way to use implantable porous scaffolds as a local gene delivery depot to enhance mRNA vaccine immunization in vitro, and in vivo when compared with conventional bolus injections. We first evaluated transfection efficiencies of single-stranded mRNA condensed and charge neutralized with two lipids (Lipofectamine Messenger MAX™ LM-MM and Stemfect™ SF) and two cationic polymers (in vivo-jetPEI™, Poly (β-amino ester)) as gene carriers. As SF demonstrated highest in vitro transfection and cell viability, it was selected for subsequent porous polymer scaffold-loading trials. Enhanced in vitro transfection of SF:mRNA nanoparticle-loaded poly (2-hydroxyethyl methacrylate) (pHEMA) scaffolds was also observed with a DC2.4 cell line. Improved sustained local release and local transgene expression were also demonstrated with SF:mRNA nanoparticle-loaded pHEMA scaffolds in vivo compared with bolus injections. Our results suggest that mRNA polyplex-loaded scaffolds may be a superior alternative to either repeated bolus immunizations or ex vivo transfection cell immunotherapies.
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影响因子：
10.8
作者：
Ali, Omar A.;Mooney, David J.
通讯作者：
Mooney, David J.
DOI：
10.1007/978-1-62703-140-0_11
发表时间：
2013-01-01
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
--
作者：
Pannier, Angela K;Segura, Tatiana
通讯作者：
Segura, Tatiana
影响因子：
10.8
作者：
Raftery, Rosanne M.;Tierney, Erica G.;O'Brien, Fergal J.
通讯作者：
O'Brien, Fergal J.
影响因子：
14
作者：
Persano S;Guevara ML;Li Z;Mai J;Ferrari M;Pompa PP;Shen H
通讯作者：
Shen H
影响因子：
64.8
作者：
Alexopoulou, L;Holt, AC;Flavell, RA
通讯作者：
Flavell, RA