Cited by 206RNA Interference and Gene DeliveryRNA and protein synthesis mechanismsRNA Research and Splicing

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

Probst, J, Weide, B, Scheel, B, Pichler, B J, Hoerr, I, Rammensee, H-G, Pascolo, S·2007·Gene Therapy

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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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Authors: Probst, J., Weide, B., Scheel, B., Pichler, B. J., Hoerr, I., Rammensee, H.-G., & Pascolo, S.
Affiliations: University of Tübingen (DE)
CureVac (Germany) (DE)
Corresponding author: Pascolo, S
ORCID: Weide, B
Pichler, B J
Rammensee, H-G
Pascolo, S
Venue: Gene Therapy
Publisher: Springer Science and Business Media LLC
Published: 2007-05-03
Volume: 14
Issue: 15
Pages: 1175-1180
ISSN: 0969-7128 (ISSN-L)
1476-5462
DOI: 10.1038/sj.gt.3302964
OpenAlex: W1991064719
Cited by: 206
References: 17
Citations by year: 2026: 4 · 2025: 14 · 2024: 13 · 2023: 22 · 2022: 18 · 2021: 36 · 2020: 11 · 2019: 10 · 2018: 11 · 2017: 4 · 2016: 8 · 2015: 10 · 2014: 8 · 2013: 5 · 2012: 6
FWCI: 2.25
Type: journal article
Language: en
Update notices: erratum (2009-05-14)
Open access: closed
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Gene Therapy (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
Keywords: mRNA delivery, skin, dermis, ion dependence, in vitro transcribed mRNA, mRNA translation, therapeutic protein expression
MeSH terms: Animals, DNA, Humans, Hydrogen-Ion Concentration, Immunohistochemistry, Injections, Subcutaneous, Luciferases, Nucleic Acids, RNA, Messenger, Skin, Transfection, Genetic Therapy, Gene Expression, Microscopy, Confocal, Mice

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

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