Efficient mRNA Delivery with mRNA Lipoplexes Prepared Using a Modified Ethanol Injection Method

Messenger RNA (mRNA)-based therapies are a novel class of therapeutics used in vaccination and protein replacement therapies for monogenic diseases. Previously, we developed a modified ethanol injection (MEI) method for small interfering RNA (siRNA) transfection, in which cationic liposome/siRNA com...

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Main Authors: Min Tang (Author), Ayane Sagawa (Author), Nodoka Inoue (Author), Satomi Torii (Author), Kana Tomita (Author), Yoshiyuki Hattori (Author)
Format: Book
Published: MDPI AG, 2023-04-01T00:00:00Z.
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042 |a dc 
100 1 0 |a Min Tang  |e author 
700 1 0 |a Ayane Sagawa  |e author 
700 1 0 |a Nodoka Inoue  |e author 
700 1 0 |a Satomi Torii  |e author 
700 1 0 |a Kana Tomita  |e author 
700 1 0 |a Yoshiyuki Hattori  |e author 
245 0 0 |a Efficient mRNA Delivery with mRNA Lipoplexes Prepared Using a Modified Ethanol Injection Method 
260 |b MDPI AG,   |c 2023-04-01T00:00:00Z. 
500 |a 10.3390/pharmaceutics15041141 
500 |a 1999-4923 
520 |a Messenger RNA (mRNA)-based therapies are a novel class of therapeutics used in vaccination and protein replacement therapies for monogenic diseases. Previously, we developed a modified ethanol injection (MEI) method for small interfering RNA (siRNA) transfection, in which cationic liposome/siRNA complexes (siRNA lipoplexes) were prepared by mixing a lipid-ethanol solution with a siRNA solution. In this study, we applied the MEI method to prepare mRNA lipoplexes and evaluated the in vitro and in vivo protein expression efficiencies. We selected six cationic lipids and three neutral helper lipids to generate 18 mRNA lipoplexes. These were composed of cationic lipids, neutral helper lipids, and polyethylene glycol-cholesteryl ether (PEG-Chol). Among them, mRNA lipoplexes containing <i>N</i>-hexadecyl-<i>N</i>,<i>N</i>-dimethylhexadecan-1-aminium bromide (DC-1-16) or 11-((1,3-bis(dodecanoyloxy)-2-((dodecanoyloxy)methyl) propan-2-yl) amino)-<i>N</i>,<i>N</i>,<i>N</i>-trimethyl-11-oxoundecan-1-aminium bromide (TC-1-12) with 1,2-dioleoyl-<i>sn</i>-glycero-3-phosphoethanolamine (DOPE) and PEG-Chol exhibited high protein expression in cells. Furthermore, mRNA lipoplexes composed of DC-1-16, DOPE, and PEG-Chol exhibited high protein expression in the lungs and spleen of mice after systemic injection and induced high antigen-specific IgG1 levels upon immunization. These results suggest that the MEI method can potentially increase the efficiency of mRNA transfection, both in vitro and in vivo. 
546 |a EN 
690 |a mRNA 
690 |a lipoplex 
690 |a delivery 
690 |a mRNA vaccine 
690 |a Pharmacy and materia medica 
690 |a RS1-441 
655 7 |a article  |2 local 
786 0 |n Pharmaceutics, Vol 15, Iss 4, p 1141 (2023) 
787 0 |n https://www.mdpi.com/1999-4923/15/4/1141 
787 0 |n https://doaj.org/toc/1999-4923 
856 4 1 |u https://doaj.org/article/e78e8b743dbf408ebc012c94e6f1915b  |z Connect to this object online.