Genetic Vaccines and Therapy

unofficial impact factor 1.86

Open Access Research

Characterization of the ribonuclease activity on the skin surface

Jochen Probst1, Sonja Brechtel2, Birgit Scheel3, Ingmar Hoerr3, Günther Jung4, Hans-Georg Rammensee1 and Steve Pascolo1*

Author Affiliations

1 Department of Immunology, Institute for Cell Biology, University of Tübingen, Auf der Morgenstelle 15, 72076 Tübingen, Germany

2 Microbial Genetics, University of Tübingen, Auf der Morgenstelle 28, 72076 Tübingen, Germany

3 Cure Vac GmbH, Paul Ehrlich Str.15, 72076 Tübingen, Germany

4 Institute for Organic Chemistry, University of Tübingen, Auf der Morgenstelle 18, 72076 Tübingen, Germany

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Genetic Vaccines and Therapy 2006, 4:4 doi:10.1186/1479-0556-4-4

Published: 29 May 2006

Abstract

The rapid degradation of ribonucleic acids (RNA) by ubiquitous ribonucleases limits the efficacy of new therapies based on RNA molecules. Therefore, our aim was to characterize the natural ribonuclease activities on the skin and in blood plasma i.e. at sites where many drugs in development are applied. On the skin surfaces of Homo sapiens and Mus musculus we observed dominant pyrimidine-specific ribonuclease activity. This activity is not prevented by a cap structure at the 5'-end of messenger RNA (mRNA) and is not primarily of a 5'- or 3'-exonuclease type. Moreover, the ribonuclease activity on the skin or in blood plasma is not inhibited by chemical modifications introduced at the 2'OH group of cytidine or uridine residues. It is, however, inhibited by the ribonuclease inhibitor RNasin® although not by the ribonuclease inhibitor SUPERase· In™. The application of our findings in the field of medical science may result in an improved efficiency of RNA-based therapies that are currently in development.