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Pharmaceutical Research

, Volume 28, Issue 9, pp 2223–2232 | Cite as

PEGylation Improves Nanoparticle Formation and Transfection Efficiency of Messenger RNA

  • Senta Üzgün
  • Gabriela Nica
  • Corinna Pfeifer
  • Michele Bosinco
  • Kai Michaelis
  • Jean-François Lutz
  • Marc Schneider
  • Joseph Rosenecker
  • Carsten Rudolph
Research Paper

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.

KEY WORDS

cationic polymers gene delivery mRNA 

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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Senta Üzgün
    • 1
    • 3
  • Gabriela Nica
    • 1
  • Corinna Pfeifer
    • 1
    • 3
  • Michele Bosinco
    • 4
  • Kai Michaelis
    • 1
  • Jean-François Lutz
    • 2
  • Marc Schneider
    • 4
  • Joseph Rosenecker
    • 1
  • Carsten Rudolph
    • 1
    • 3
  1. 1.Division of Molecular Pulmonology, Department of PediatricsLudwig Maximilians University of MunichMunichGermany
  2. 2.Fraunhofer Institute for Applied Polymer ResearchPotsdam-GolmGermany
  3. 3.Department of Pharmaceutical TechnologyFree University of BerlinBerlinGermany
  4. 4.Pharmaceutical NanotechnologySaarland UniversitySaarbrückenGermany

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