Influence of Lipid Composition of Cationic Liposomes 2X3-DOPE on mRNA Delivery into Eukaryotic Cells
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
Affiliations
Vera Vysochinskaya
Smorodintsev Research Institute of Influenza, 15/17 Ulitsa Professora Popova, 197376 St. Petersburg, Russia
Sergey Shishlyannikov
Smorodintsev Research Institute of Influenza, 15/17 Ulitsa Professora Popova, 197376 St. Petersburg, Russia
Yana Zabrodskaya
Smorodintsev Research Institute of Influenza, 15/17 Ulitsa Professora Popova, 197376 St. Petersburg, Russia
Elena Shmendel
Lomonosov Institute of Fine Chemical Technologies, MIREA—Russian Technological University, 86 Vernadsky Ave, 119571 Moscow, Russia
Sergey Klotchenko
Smorodintsev Research Institute of Influenza, 15/17 Ulitsa Professora Popova, 197376 St. Petersburg, Russia
Olga Dobrovolskaya
Smorodintsev Research Institute of Influenza, 15/17 Ulitsa Professora Popova, 197376 St. Petersburg, Russia
Nina Gavrilova
Smorodintsev Research Institute of Influenza, 15/17 Ulitsa Professora Popova, 197376 St. Petersburg, Russia
Darya Makarova
Lomonosov Institute of Fine Chemical Technologies, MIREA—Russian Technological University, 86 Vernadsky Ave, 119571 Moscow, Russia
Marina Plotnikova
Smorodintsev Research Institute of Influenza, 15/17 Ulitsa Professora Popova, 197376 St. Petersburg, Russia
Ekaterina Elpaeva
Smorodintsev Research Institute of Influenza, 15/17 Ulitsa Professora Popova, 197376 St. Petersburg, Russia
Andrey Gorshkov
Smorodintsev Research Institute of Influenza, 15/17 Ulitsa Professora Popova, 197376 St. Petersburg, Russia
Dmitry Moshkoff
Institute of Biomedical Systems and Biotechnology, Peter the Great Saint Petersburg Polytechnic University, 29 Ulitsa Polytechnicheskaya, 194064 St. Petersburg, Russia
Mikhail Maslov
Lomonosov Institute of Fine Chemical Technologies, MIREA—Russian Technological University, 86 Vernadsky Ave, 119571 Moscow, Russia
Andrey Vasin
Smorodintsev Research Institute of Influenza, 15/17 Ulitsa Professora Popova, 197376 St. Petersburg, Russia
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.
