caa a22 4500 445312076 CHVBK 20180317142633.0 cr unu---uuuuu 170323e20110901xx s 000 0 eng 10.1007/s11095-011-0464-z doi (NATIONALLICENCE)springer-10.1007/s11095-011-0464-z PEGylation Improves Nanoparticle Formation and Transfection Efficiency of Messenger RNA [Elektronische Daten] [Senta Üzgün, Gabriela Nica, Corinna Pfeifer, Michele Bosinco, Kai Michaelis, Jean-François Lutz, Marc Schneider, Joseph Rosenecker, Carsten Rudolph] ABSTRACT: Purpose: Cationic polymers have been intensively investigated for plasmid-DNA (pDNA), but few studies addressed their use for messenger-RNA (mRNA) delivery. We analyzed two types of polymers, linear polyethylenimine (l-PEI) and poly-N,N-dimethylaminoethylmethacrylate P(DMAEMA), to highlight specific requirements for the design of mRNA delivery reagents. The effect of PEGylation was investigated using P(DMAEMA-co-OEGMA) copolymer. Methods: The influence of polymer structure on mRNA binding and particle formation was assessed in a side-by-side comparison with pDNA by methods such as agarose-retardation assay and scanning probe microscopy. Transfection studies were performed on bronchial epithelial cells. Results: Binding of cationic polymers inversely correlated with type of nucleic acid. Whereas P(DMAEMA) bound strongly to pDNA, only weak mRNA binding was observed, which was vice versa for l-PEI. Both polymers resulted in self-assembled nanoparticles forming pDNA complexes of irregular round shape; mRNA particles were significantly smaller and more distinct. Surprisingly, PEGylation improved mRNA binding and transfection efficiency contrary to observations made with pDNA. Co-transfections with free polymer improved mRNA transfection. Conclusions: Gene delivery requires tailor-made design for each type of nucleic acid. PEGylation influenced mRNA-polymer binding efficiency and transfection and may provide a method of further improving mRNA delivery. Springer Science+Business Media, LLC, 2011 cationic polymers nationallicence gene delivery nationallicence mRNA nationallicence Üzgün Senta Division of Molecular Pulmonology, Department of Pediatrics, Ludwig Maximilians University of Munich, Lindwurmstr. 2a, 80337, Munich, Germany aut Nica Gabriela Division of Molecular Pulmonology, Department of Pediatrics, Ludwig Maximilians University of Munich, Lindwurmstr. 2a, 80337, Munich, Germany aut Pfeifer Corinna Division of Molecular Pulmonology, Department of Pediatrics, Ludwig Maximilians University of Munich, Lindwurmstr. 2a, 80337, Munich, Germany aut Bosinco Michele Pharmaceutical Nanotechnology, Saarland University, Campus A4 1, 66123, Saarbrücken, Germany aut Michaelis Kai Division of Molecular Pulmonology, Department of Pediatrics, Ludwig Maximilians University of Munich, Lindwurmstr. 2a, 80337, Munich, Germany aut Lutz Jean-François Fraunhofer Institute for Applied Polymer Research, 14476, Potsdam-Golm, Germany aut Schneider Marc Pharmaceutical Nanotechnology, Saarland University, Campus A4 1, 66123, Saarbrücken, Germany aut Rosenecker Joseph Division of Molecular Pulmonology, Department of Pediatrics, Ludwig Maximilians University of Munich, Lindwurmstr. 2a, 80337, Munich, Germany aut Rudolph Carsten Division of Molecular Pulmonology, Department of Pediatrics, Ludwig Maximilians University of Munich, Lindwurmstr. 2a, 80337, Munich, Germany aut Pharmaceutical Research Springer US; http://www.springer-ny.com 28/9(2011-09-01), 2223-2232 0724-8741 28:9<2223 2011 28 11095 https://doi.org/10.1007/s11095-011-0464-z text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11095-011-0464-z text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Üzgün Senta Division of Molecular Pulmonology, Department of Pediatrics, Ludwig Maximilians University of Munich, Lindwurmstr. 2a, 80337, Munich, Germany aut NATIONALLICENCE 700 1- Nica Gabriela Division of Molecular Pulmonology, Department of Pediatrics, Ludwig Maximilians University of Munich, Lindwurmstr. 2a, 80337, Munich, Germany aut NATIONALLICENCE 700 1- Pfeifer Corinna Division of Molecular Pulmonology, Department of Pediatrics, Ludwig Maximilians University of Munich, Lindwurmstr. 2a, 80337, Munich, Germany aut NATIONALLICENCE 700 1- Bosinco Michele Pharmaceutical Nanotechnology, Saarland University, Campus A4 1, 66123, Saarbrücken, Germany aut NATIONALLICENCE 700 1- Michaelis Kai Division of Molecular Pulmonology, Department of Pediatrics, Ludwig Maximilians University of Munich, Lindwurmstr. 2a, 80337, Munich, Germany aut NATIONALLICENCE 700 1- Lutz Jean-François Fraunhofer Institute for Applied Polymer Research, 14476, Potsdam-Golm, Germany aut NATIONALLICENCE 700 1- Schneider Marc Pharmaceutical Nanotechnology, Saarland University, Campus A4 1, 66123, Saarbrücken, Germany aut NATIONALLICENCE 700 1- Rosenecker Joseph Division of Molecular Pulmonology, Department of Pediatrics, Ludwig Maximilians University of Munich, Lindwurmstr. 2a, 80337, Munich, Germany aut NATIONALLICENCE 700 1- Rudolph Carsten Division of Molecular Pulmonology, Department of Pediatrics, Ludwig Maximilians University of Munich, Lindwurmstr. 2a, 80337, Munich, Germany aut NATIONALLICENCE 773 0- Pharmaceutical Research Springer US; http://www.springer-ny.com 28/9(2011-09-01), 2223-2232 0724-8741 28:9<2223 2011 28 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer