Ready-to-Use-Type Lyophilized Lipid Nanoparticle Formulation for the Postencapsulation of Messenger RNA
Ready-to-Use-Type Lyophilized Lipid Nanoparticle Formulation for the Postencapsulation of Messenger RNA
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用于信使 RNA 后封装的即用型冻干脂质纳米颗粒制剂
DOI：
10.1021/acsnano.2c10501
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发表时间：
2023
期刊：
影响因子：
17.1
通讯作者：
Taneichi Sakura
中科院分区：
文献类型：
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作者：
Tanaka Hiroki;Hagiwara Shinya;Shirane Daiki;Yamakawa Takuma;Sato Yuka;Matsumoto Chika;Ishizaki Kota;Hishinuma Miho;Chida Katsuyuki;Sasaki Kasumi;Yonemochi Etsuo;Ueda Keisuke;Higashi Kenjirou;Moribe Kunikazu;Tadokoro Takashi;Maenaka Katsumi;Taneichi Sakura
基于封装在脂质纳米颗粒（mRNA-LNP）中的体外转录mRNA（IVT-mRNA）的临床成功，研究人员越来越需要测试他们自己的生物学发现是否适用于基于mRNA的治疗。然而，制造这种纳米颗粒所需的设备和/或技术诀窍通常是无法获得的。为了鼓励mRNA疗法的更多创新，制备mRNA-LNP的简单方法是先决条件。在这项研究中，我们报告了一种将IVT-mRNA包封到LNP中的方法，即用型空冻干LNP（LNP（RtoU））制剂与IVT-mRNA溶液再水化，然后加热。与通过常规微流体混合制备的mRNA-LNP相比，所得mRNA-LNP（RtoU）具有类似的颗粒内结构。在体内基因组编辑中，使用含有共包封的Cas9-mRNA和小向导RNA的LNP（RtoU）实现了这些类型的mRNA-LNP的有希望的应用。
Based on the clinical success of anin vitrotranscribed mRNA (IVT-mRNA) that is encapsulated in lipid nanoparticles (mRNA-LNPs), there is a growing demand by researchers to test whether their own biological findings might be applicable for use in mRNA-based therapeutics. However, the equipment and/or know-how required for manufacturing such nanoparticles is often inaccessible. To encourage more innovation in mRNA therapeutics, a simple method for preparing mRNA-LNPs is prerequisite. In this study, we report on a method for encapsulating IVT-mRNA into LNPs by rehydrating a Ready-to-Use empty freeze-dried LNP (LNPs(RtoU)) formulation with IVT-mRNA solution followed by heating. The resulting mRNA-LNPs(RtoU) had a similar intraparticle structure compared to the mRNA-LNPs prepared by conventional microfluidic mixing.In vivogenome editing, a promising application of these types of mRNA-LNPs, was accomplished using the LNPs(RtoU) containing co-encapsulated Cas9-mRNA and a small guide RNA.