PEGylation Improves Nanoparticle Formation and Transfection Efficiency of Messenger RNA View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2011-09

AUTHORS

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. More... »

PAGES

2223-2232

Journal

TITLE

Pharmaceutical Research

ISSUE

9

VOLUME

28

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1007/s11095-011-0464-z

    DOI

    http://dx.doi.org/10.1007/s11095-011-0464-z

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1016398292

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/21594715


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