A Post-Encapsulation Method for the Preparation of mRNA-LNPs via the Nucleic Acid-Bridged Fusion of mRNA-Free LNPs

被引：0

作者：

Tanaka, Hiroki ^{[1
,2
]}

Sato, Yuka ^{[3
]}

Nakabayashi, Tomoya ^{[1
]}

Tanaka, Akari ^{[1
]}

Nishio, Kazuma ^{[1
]}

Matsumoto, Chika ^{[1
]}

Matsumaru, Atsuya ^{[1
]}

Yamakawa, Takuma ^{[3
]}

Ishizaki, Kota ^{[3
]}

Ueda, Keisuke ^{[4
]}

Higashi, Kenjirou ^{[4
]}

Moribe, Kunikazu ^{[4
]}

Nakai, Yuta ^{[5
]}

Tange, Kota ^{[5
]}

Akita, Hidetaka ^{[1
,2
]}

机构：

[1] Tohoku Univ, Grad Sch Pharmaceut Sci, Lab DDS Design & Drug Disposit, Sendai, Miyagi 9808578, Japan

[2] Osaka Univ, Ctr Adv Modal DDS, Osaka 5650871, Japan

[3] Chiba Univ, Grad Sch Pharmaceut Sci, Lab DDS Design & Drug Disposit, Chiba, Chiba 2600856, Japan

[4] Chiba Univ, Grad Sch Pharmaceut Sci, Lab Pharmaceut Technol, Chiba, Chiba 2600856, Japan

[5] NOF Corp, Life Sci Res Lab, Kawasaki, Kanagawa 2100865, Japan

来源：

NANO LETTERS | 2025年 / 25卷 / 16期

关键词：

Lipid nanoparticles; Gene therapy; mRNA vaccines; Drug delivery systems; LIPID NANOPARTICLES; SIRNA; ENTRAPMENT;

D O I：

暂无

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Lipid nanoparticles with encapsulated mRNA (mRNA-LNPs) have become key modalities for personalized medicines and RNA vaccines. Once the platform technology is established, the mRNA-LNPs could be applicable to a variety of protein-based therapeutic strategies. A post-encapsulation method, in which the mRNA solution is incubated with preformed mRNA-free LNPs to prepare the mRNA-LNPs, would accelerate the development of RNA-based therapeutics since even nonexperts could manufacture the mRNA-LNPs. In this study, we describe that the post-encapsulation of mRNA into mRNA-free LNPs is accompanied by "nucleic acid-bridged fusion" of them. The adsorption of mRNA onto mRNA-free LNPs via electrostatic interactions and the internalization of mRNA into the LNPs via particle-to-particle fusion are two steps that occur at different levels of pH. To complete post-encapsulation using only one-step mixing, the pH must be controlled within a limited region where both processes occur simultaneously. The size of the mRNA-free LNPs determines the effectiveness of mRNA loading.

引用

页码：6445 / 6453

页数：9

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