title: PEGylation improves nanoparticle formation and transfection efficiency of messenger RNA.
abstract: OBJECTIVE
  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.
authors: Division of Molecular Pulmonology, Department of Pediatrics, Ludwig Maximilians University of Munich, Lindwurmstr. 2a, 80337 Munich, Germany.
authors: Senta
authors: S
authors: Uzgün
authors: Gabriela
authors: G
authors: Nica
authors: Corinna
authors: C
authors: Pfeifer
authors: Michele
authors: M
authors: Bosinco
authors: Kai
authors: K
authors: Michaelis
authors: Jean-François
authors: JF
authors: Lutz
authors: Marc
authors: M
authors: Schneider
authors: Joseph
authors: J
authors: Rosenecker
authors: Carsten
authors: C
authors: Rudolph
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