Influence of Lipid Composition of Cationic Liposomes 2X3-DOPE on mRNA Delivery into Eukaryotic Cells

The design of cationic liposomes for efficient mRNA delivery can significantly improve mRNA-based therapies. Lipoplexes based on polycationic lipid 1,26-bis(cholest-5-en-3β-yloxycarbonylamino)-7,11,16,20-tetraazahexacosane tetrahydrochloride (2X3) and helper lipid 1,2-dioleoyl-sn-glycero-3-phosphoet...

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Main Authors: Vera Vysochinskaya, Sergey Shishlyannikov, Yana Zabrodskaya, Elena Shmendel, Sergey Klotchenko, Olga Dobrovolskaya, Nina Gavrilova, Darya Makarova, Marina Plotnikova, Ekaterina Elpaeva, Andrey Gorshkov, Dmitry Moshkoff, Mikhail Maslov, Andrey Vasin
Format: Article
Language:English
Published: MDPI AG 2022-12-01
Series:Pharmaceutics
Subjects:
Online Access:https://www.mdpi.com/1999-4923/15/1/8
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author Vera Vysochinskaya
Sergey Shishlyannikov
Yana Zabrodskaya
Elena Shmendel
Sergey Klotchenko
Olga Dobrovolskaya
Nina Gavrilova
Darya Makarova
Marina Plotnikova
Ekaterina Elpaeva
Andrey Gorshkov
Dmitry Moshkoff
Mikhail Maslov
Andrey Vasin
author_facet Vera Vysochinskaya
Sergey Shishlyannikov
Yana Zabrodskaya
Elena Shmendel
Sergey Klotchenko
Olga Dobrovolskaya
Nina Gavrilova
Darya Makarova
Marina Plotnikova
Ekaterina Elpaeva
Andrey Gorshkov
Dmitry Moshkoff
Mikhail Maslov
Andrey Vasin
author_sort Vera Vysochinskaya
collection DOAJ
description The design of cationic liposomes for efficient mRNA delivery can significantly improve mRNA-based therapies. Lipoplexes based on polycationic lipid 1,26-bis(cholest-5-en-3β-yloxycarbonylamino)-7,11,16,20-tetraazahexacosane tetrahydrochloride (2X3) and helper lipid 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) were formulated in different molar ratios (1:1, 1:2, 1:3) to efficiently deliver model mRNAs to BHK-21 and A549. The objective of this study was to examine the effect of 2X3-DOPE composition as well as lipid-to-mRNA ratio (amino-to-phosphate group ratio, N/P) on mRNA transfection. We found that lipoplex-mediated transfection efficiency depends on both liposome composition and the N/P ratio. Lipoplexes with an N/P ratio of 10/1 showed nanometric hydrodynamic size, positive ζ potential, maximum loading, and transfection efficiency. Liposomes 2X3-DOPE (1:3) provided the superior delivery of both mRNA coding firefly luciferase and mRNA-eGFP into BHK-21 cells and A549 cells, compared with commercial Lipofectamine MessengerMax.
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spelling doaj.art-30f92b9654fa4a65a5bee303555dceea2023-11-30T23:56:22ZengMDPI AGPharmaceutics1999-49232022-12-01151810.3390/pharmaceutics15010008Influence of Lipid Composition of Cationic Liposomes 2X3-DOPE on mRNA Delivery into Eukaryotic CellsVera Vysochinskaya0Sergey Shishlyannikov1Yana Zabrodskaya2Elena Shmendel3Sergey Klotchenko4Olga Dobrovolskaya5Nina Gavrilova6Darya Makarova7Marina Plotnikova8Ekaterina Elpaeva9Andrey Gorshkov10Dmitry Moshkoff11Mikhail Maslov12Andrey Vasin13Smorodintsev Research Institute of Influenza, 15/17 Ulitsa Professora Popova, 197376 St. Petersburg, RussiaSmorodintsev Research Institute of Influenza, 15/17 Ulitsa Professora Popova, 197376 St. Petersburg, RussiaSmorodintsev Research Institute of Influenza, 15/17 Ulitsa Professora Popova, 197376 St. Petersburg, RussiaLomonosov Institute of Fine Chemical Technologies, MIREA—Russian Technological University, 86 Vernadsky Ave, 119571 Moscow, RussiaSmorodintsev Research Institute of Influenza, 15/17 Ulitsa Professora Popova, 197376 St. Petersburg, RussiaSmorodintsev Research Institute of Influenza, 15/17 Ulitsa Professora Popova, 197376 St. Petersburg, RussiaSmorodintsev Research Institute of Influenza, 15/17 Ulitsa Professora Popova, 197376 St. Petersburg, RussiaLomonosov Institute of Fine Chemical Technologies, MIREA—Russian Technological University, 86 Vernadsky Ave, 119571 Moscow, RussiaSmorodintsev Research Institute of Influenza, 15/17 Ulitsa Professora Popova, 197376 St. Petersburg, RussiaSmorodintsev Research Institute of Influenza, 15/17 Ulitsa Professora Popova, 197376 St. Petersburg, RussiaSmorodintsev Research Institute of Influenza, 15/17 Ulitsa Professora Popova, 197376 St. Petersburg, RussiaInstitute of Biomedical Systems and Biotechnology, Peter the Great Saint Petersburg Polytechnic University, 29 Ulitsa Polytechnicheskaya, 194064 St. Petersburg, RussiaLomonosov Institute of Fine Chemical Technologies, MIREA—Russian Technological University, 86 Vernadsky Ave, 119571 Moscow, RussiaSmorodintsev Research Institute of Influenza, 15/17 Ulitsa Professora Popova, 197376 St. Petersburg, RussiaThe design of cationic liposomes for efficient mRNA delivery can significantly improve mRNA-based therapies. Lipoplexes based on polycationic lipid 1,26-bis(cholest-5-en-3β-yloxycarbonylamino)-7,11,16,20-tetraazahexacosane tetrahydrochloride (2X3) and helper lipid 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) were formulated in different molar ratios (1:1, 1:2, 1:3) to efficiently deliver model mRNAs to BHK-21 and A549. The objective of this study was to examine the effect of 2X3-DOPE composition as well as lipid-to-mRNA ratio (amino-to-phosphate group ratio, N/P) on mRNA transfection. We found that lipoplex-mediated transfection efficiency depends on both liposome composition and the N/P ratio. Lipoplexes with an N/P ratio of 10/1 showed nanometric hydrodynamic size, positive ζ potential, maximum loading, and transfection efficiency. Liposomes 2X3-DOPE (1:3) provided the superior delivery of both mRNA coding firefly luciferase and mRNA-eGFP into BHK-21 cells and A549 cells, compared with commercial Lipofectamine MessengerMax.https://www.mdpi.com/1999-4923/15/1/8cationic lipidsmRNAtransfectionliposomesnon-viral delivery systems
spellingShingle Vera Vysochinskaya
Sergey Shishlyannikov
Yana Zabrodskaya
Elena Shmendel
Sergey Klotchenko
Olga Dobrovolskaya
Nina Gavrilova
Darya Makarova
Marina Plotnikova
Ekaterina Elpaeva
Andrey Gorshkov
Dmitry Moshkoff
Mikhail Maslov
Andrey Vasin
Influence of Lipid Composition of Cationic Liposomes 2X3-DOPE on mRNA Delivery into Eukaryotic Cells
Pharmaceutics
cationic lipids
mRNA
transfection
liposomes
non-viral delivery systems
title Influence of Lipid Composition of Cationic Liposomes 2X3-DOPE on mRNA Delivery into Eukaryotic Cells
title_full Influence of Lipid Composition of Cationic Liposomes 2X3-DOPE on mRNA Delivery into Eukaryotic Cells
title_fullStr Influence of Lipid Composition of Cationic Liposomes 2X3-DOPE on mRNA Delivery into Eukaryotic Cells
title_full_unstemmed Influence of Lipid Composition of Cationic Liposomes 2X3-DOPE on mRNA Delivery into Eukaryotic Cells
title_short Influence of Lipid Composition of Cationic Liposomes 2X3-DOPE on mRNA Delivery into Eukaryotic Cells
title_sort influence of lipid composition of cationic liposomes 2x3 dope on mrna delivery into eukaryotic cells
topic cationic lipids
mRNA
transfection
liposomes
non-viral delivery systems
url https://www.mdpi.com/1999-4923/15/1/8
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