Expression of therapeutic proteins after delivery of chemically modified mRNA in mice View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2011-02

AUTHORS

Michael S D Kormann, Günther Hasenpusch, Manish K Aneja, Gabriela Nica, Andreas W Flemmer, Susanne Herber-Jonat, Marceline Huppmann, Lauren E Mays, Marta Illenyi, Andrea Schams, Matthias Griese, Iris Bittmann, Rupert Handgretinger, Dominik Hartl, Joseph Rosenecker, Carsten Rudolph

ABSTRACT

Current viral vectors for gene therapy are associated with serious safety concerns, including leukemogenesis, and nonviral vectors are limited by low gene transfer efficiency. Here we investigate the therapeutic utility of chemically modified mRNA as an alternative to DNA-based gene therapy. A combination of nucleotide modifications abrogates mRNA interaction with Toll-like receptor (TLR)3, TLR7, TLR8 and retinoid-inducible gene I (RIG-I), resulting in low immunogenicity and higher stability in mice. A single intramuscular injection of modified murine erythropoietin mRNA raises the average hematocrit in mice from 51.5% to 64.2% after 28 days. In a mouse model of a lethal congenital lung disease caused by a lack of surfactant protein B (SP-B), twice weekly local application of an aerosol of modified SP-B mRNA to the lung restored 71% of the wild-type SP-B expression, and treated mice survived until the predetermined end of the study after 28 days. More... »

PAGES

154

Journal

TITLE

Nature Biotechnology

ISSUE

2

VOLUME

29

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/nbt.1733

    DOI

    http://dx.doi.org/10.1038/nbt.1733

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1002080286

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/21217696


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