Leveraging Biological Buffers for Efficient Messenger RNA Delivery via Lipid Nanoparticles.
Leveraging Biological Buffers for Efficient Messenger RNA Delivery via Lipid Nanoparticles.
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DOI：
10.1021/acs.molpharmaceut.2c00587
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发表时间：
2022-11-07
影响因子：
4.9
通讯作者：
Sahay G
中科院分区：
文献类型：
--
作者：
Henderson MI;Eygeris Y;Jozic A;Herrera M;Sahay G
在COVID-19大流行期间，含有信使RNA的脂质纳米颗粒（mRNA-LNP）凭借其实现的潜力，已成为非病毒递送系统的前沿。在这里，我们研究了常用的生物缓冲液对mRNA-LNP的性能和耐久性的影响。我们测试了三种常见缓冲液- HEPES、Tris和磷酸盐缓冲盐水-在单个受控冻融（FT）循环之前和之后与DLin-MC 3-DMA mRNA-LNP制剂的相容性。我们假设缓冲液组成会影响脂质-水相分离。事实上，缓冲液施加LNP形态的结构变化，如电子显微镜，差示扫描量热法和膜流动性测定所示。我们采用体外和体内模型来测量mRNA转染，并发现与PBS相比，Tris或HEPES缓冲的LNP产生更好的冷冻保护和转染效率。了解各种缓冲液对LNP形态和功效的影响为长期储存后保持LNP的稳定性提供了有价值的见解。
Lipid nanoparticles containing messenger RNA (mRNA-LNPs) have launched to the forefront of non-viral delivery systems with their realized potential during the COVID-19 pandemic. Here, we investigate the impact of commonly used biological buffers on performance and durability of mRNA-LNPs. We tested the compatibility of three common buffers – HEPES, Tris, and phosphate-buffered saline - with a DLin-MC3-DMA mRNA-LNP formulation before and after a single controlled freeze-thaw (FT) cycle. We hypothesized that buffer composition would affect lipid-aqueous phase separation. Indeed, the buffers imposed structural changes in LNP morphology as indicated by electron microscopy, differential scanning calorimetry, and membrane fluidity assays. We employed in vitro and in vivo models to measure mRNA transfection and found that Tris or HEPES-buffered LNPs yielded better cryoprotection and transfection efficiency compared to PBS. Understanding the effects of various buffers on LNP morphology and efficacy provides valuable insights in maintaining the stability of LNPs after long-term storage.
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影响因子：
6.6
作者：
Herrera M;Kim J;Eygeris Y;Jozic A;Sahay G
通讯作者：
Sahay G
DOI：
10.1038/s41578-021-00358-0
发表时间：
2021
期刊：
Nature reviews. Materials
影响因子：
--
作者：
Hou X;Zaks T;Langer R;Dong Y
通讯作者：
Dong Y
影响因子：
5.9
作者：
Munson MJ;O'Driscoll G;Silva AM;Lázaro-Ibáñez E;Gallud A;Wilson JT;Collén A;Esbjörner EK;Sabirsh A
通讯作者：
Sabirsh A
影响因子：
5.9
作者：
Carrasco MJ;Alishetty S;Alameh MG;Said H;Wright L;Paige M;Soliman O;Weissman D;Cleveland TE 4th;Grishaev A;Buschmann MD
通讯作者：
Buschmann MD
影响因子：
10.8
作者：
Kauffman, Kevin J.;Dorkin, J. Robert;Anderson, Daniel G.
通讯作者：
Anderson, Daniel G.