A facile method to prepare non-cationic mRNA lipid-nanoparticles based on frame guided assembly strategy
A facile method to prepare non-cationic mRNA lipid-nanoparticles based on frame guided assembly strategy
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DOI：
10.1016/j.nantod.2023.101991
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发表时间：
2023-10
期刊：
影响因子：
17.4
通讯作者：
Yujie Li;Wei Yuan;Xiancheng Tian;Chenyou Zhu;Xin Li;Ruofan Chen;Ziyang Hao;Yuanchen Dong;Dongsheng Liu
中科院分区：
文献类型：
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作者：
Yujie Li;Wei Yuan;Xiancheng Tian;Chenyou Zhu;Xin Li;Ruofan Chen;Ziyang Hao;Yuanchen Dong;Dongsheng Liu
近年来，脂质纳米颗粒(LNP)形成的信使RNA(MRNA)已成为疫苗开发和蛋白质替代治疗的一种有前途的工具。然而，目前的LNPs中的阳离子或可电离的脂质成分也带来了毒性和免疫原性的担忧。在这项研究中，我们开发了一种新的阳离子脂类非依赖性策略，通过框架引导组装(FGA)来制备mRNA-LNPs。一般的信使核糖核酸紧凑方法是将长链的信使核糖核酸折叠成致密的信使核糖核酸颗粒，然后作为两亲性框架引导磷脂通过疏水相互作用进行组装。我们还展示了我们的mRNA-LNPs的高信使核糖核酸包封率、良好的稳定性和细胞内递送能力，有望成为信使核糖核酸治疗和疫苗的一种有前途的工具。
In recent years, lipid nanoparticle (LNP)-formulated messenger RNA (mRNA) has become a promising tool in vaccine development and protein replacement therapy. However, the cationic or ionizable lipid components in the current LNPs also bring the concerns on toxicity and immunogenicity. In this study, we have developed a novel cationic lipid-independent strategy to prepare mRNA-LNPs through frame-guided assembly (FGA). A general mRNA compacting method has been demonstrated to fold long mRNA strands into compact mRNA particles, which was subsequently served as the amphiphilic frames to guide the assembly of phospholipid through hydrophobic interaction. We have also demonstrated high mRNA encapsulation efficiency, good stability and intracellular delivery capability of our mRNA-LNPs, which is expected as a promising tool in mRNA therapeutics and vaccines.