Injectable Biodegradable Chitosan-Alginate 3D Porous Gel Scaffold for mRNA Vaccine Delivery.
Injectable Biodegradable Chitosan-Alginate 3D Porous Gel Scaffold for mRNA Vaccine Delivery.
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DOI：
10.1002/mabi.201800242
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发表时间：
2018-11
影响因子：
4.6
通讯作者：
Jingxuan Yan;Ruying Chen;Hong Zhang;J. Bryers
中科院分区：
文献类型：
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作者：
Jingxuan Yan;Ruying Chen;Hong Zhang;J. Bryers
mRNA疫苗已被证明在刺激体液和细胞免疫应答方面比基于蛋白/肽的疫苗更稳定、有效和特异性。然而，mRNA在体内的快速降解速率和低转染效率阻碍了其在疫苗接种中的潜力。最近的基因传递研究集中在非病毒疫苗载体和可植入或可注射的传递系统，以提高转基因在体内的表达。在这里，可注射的壳聚糖-海藻酸凝胶支架的mRNA疫苗的局部交付的报告。量化凝胶支架的生物降解速率和生物相容性。在体内评价支架介导的mRNA体内转基因表达以及卵清蛋白抗原特异性细胞和体液免疫应答。荧光素酶报告蛋白的表达导致的mRNA脂质体负载的凝胶支架是全身注射的5倍。与裸mRNA或mRNA：脂质复合物的全身注射相比，在体内支架介导的mRNA脂质复合物递送中观察到T细胞增殖和IFN-γ分泌水平升高。此外，对于支架介导的mRNA lipoplex递送，早在第1周就观察到体液反应（卵清蛋白抗原特异性IgG水平），而基于蛋白质的免疫直到注射后2周才引起IgG产生。结果表明，可注射支架mRNA疫苗递送可能是传统核酸免疫方法的可行替代方案。
mRNA vaccines have proven to be more stable, effective, and specific than protein/peptide-based vaccines in stimulating both humoral and cellular immune response. However, mRNA's fast degradation rate and low-transfection efficiency in vivo impede its potential in vaccination. Recent research in gene delivery has focused on nonviral vaccine carriers and either implantable or injectable delivery systems to improve transgene expression in vivo. Here, an injectable chitosan-alginate gel scaffold for the local delivery of mRNA vaccines is reported. Gel scaffold biodegradation rates and biocompatibility are quantified. Scaffold-mediated mRNA in vivo transgene expression as well as ovalbumin antigen specific cellular and humoral immune responses are evaluated in vivo. Luciferase reporter protein expression resulting from mRNA lipoplex-loaded gel scaffolds is five times higher than systemic injection. Compared to systemic injections of naked mRNA or mRNA:lipoplexes, elevated levels of T cell proliferation and IFN-γ secretion are seen with in vivo scaffold-mediated mRNA lipoplex delivery. Furthermore, a humoral response (ovalbumin antigen specific IgG levels) is observed as early as week 1 for scaffold-mediated mRNA lipoplex delivery, while protein-based immunization did not elicit IgG production until 2 weeks post-injection. Results suggest that injectable scaffold mRNA vaccine delivery maybe a viable alternative to traditional nucleic acid immunization methods.