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Spontaneous cellular uptake of exogenous messenger RNA in vivo is nucleic acid-specific, saturable and ion dependent

Gene Therapy volume 14, pages 1175–1180 (2007)Cite this article

A Corrigendum to this article was published on 14 May 2009

Abstract

The development of new treatments in the post-genomic era requires methods for safe delivery of foreign genetic information in vivo. As a transient, natural and controllable alternative to recombinant viruses or plasmid DNA (pDNA), purified or in vitro transcribed messenger RNA (mRNA) can be used for the expression of any therapeutic protein in vitro and in vivo. As it has been shown previously, the simple injection of naked mRNA results in local uptake and expression. We show here that this process, in the skin, can greatly be modulated according to the injection solution composition and blocked by an excess of competing nucleic acids or a drug affecting cytosolic mobility. Different cell types at the site of injection can take up the foreign nucleic acid molecules and the protein translated from this is detected for no more than a few days. To test this gene transfer method in humans, we produced in vitro transcribed mRNA under good manufacturing practice (GMP) conditions in a dedicated facility. After injection into the human dermis, we could document the translation of the exogenous mRNA. Our results pave the way toward the use of mRNA as a vehicle for transient gene delivery in humans.

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Acknowledgements

This work was supported by the Fritz-Bender Stiftung. JP was supported by the DFG Graduiertenkolleg ‘infektionsbiologie’ 685 of Tübingen.

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Authors and Affiliations

  1. Department of Immunology, Institute for Cell Biology, University of Tübingen, Tübingen, Germany

    J Probst, B Scheel, H-G Rammensee & S Pascolo

  2. CureVac GmbH, Tübingen, Germany

    J Probst, B Scheel, I Hoerr & S Pascolo

  3. Department of Dermatology, University of Tübingen, Tübingen, Germany

    B Weide

  4. Department of Radiology, Laboratory for Preclinical Imaging and Imaging Technology, University of Tübingen, Tübingen, Germany

    B J Pichler

Authors
  1. J Probst
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  2. B Weide
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  3. B Scheel
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  4. B J Pichler
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  5. I Hoerr
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  6. H-G Rammensee
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  7. S Pascolo
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Corresponding author

Correspondence to S Pascolo.

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Supplementary Information accompanies the paper on Gene Therapy website (http://www.nature.com/gt)

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Probst, J., Weide, B., Scheel, B. et al. Spontaneous cellular uptake of exogenous messenger RNA in vivo is nucleic acid-specific, saturable and ion dependent. Gene Ther 14, 1175–1180 (2007). https://doi.org/10.1038/sj.gt.3302964

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  • DOI: https://doi.org/10.1038/sj.gt.3302964

Keywords

  • RNA-transfection
  • DNA-transfection
  • endosomes
  • calcium
  • GMP

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