| 标题 |
 Polymer–mRNA complexes for monocyte-trafficked, lymph node-targeted cancer vaccination 相关领域
核糖核酸
化学
计算生物学
生物化学
生物
基因
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10.1038/s41573-025-01237-x
Doi
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| 其它 | Lymph nodes are the primary sites where adaptive immunity is initiated, yet most messenger RNA cancer vaccines reach them inefficiently and instead accumulate in organs such as the liver, limiting therapeutic potency and increasing systemic toxicity. Here we developed a transferrin receptor-associating polyplex formed by electrostatic complexation of mRNA with low-molecular-weight polyethylenimine that had been chemically modified with cyclic disulfide monomers to enhance nucleic acid binding stability, enable thiol-based transferrin receptor engagement and reduce off-target liver uptake. After subcutaneous administration, these polyplexes activated innate immunity, rapidly recruited monocytes with high transferrin receptor expression and bound these cells through cyclic disulfide-mediated interactions. Monocytes then trafficked the vaccine to draining lymph nodes, where mRNA translation and antigen presentation occurred. |
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