Characterization of the ribonuclease activity on the skin surface

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BioMed Central

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Characterization of the ribonuclease activity on the skin surface Jochen Probst1, Sonja Brechtel2, Birgit Scheel3, Ingmar Hoerr3, Günther Jung4, Hans-Georg Rammensee1 and Steve Pascolo*1 Address: 1Department of Immunology, Institute for Cell Biology, University of Tübingen, Auf der Morgenstelle 15, 72076 Tübingen, Germany, 2Microbial Genetics, University of Tübingen, Auf der Morgenstelle 28, 72076 Tübingen, Germany, 3Cure Vac GmbH, Paul Ehrlich Str.15, 72076 Tübingen, Germany and 4Institute for Organic Chemistry, University of Tübingen, Auf der Morgenstelle 18, 72076 Tübingen, Germany Email: Jochen Probst - [email protected]; Sonja Brechtel - [email protected]; Birgit Scheel - [email protected]; Ingmar Hoerr - [email protected]; Günther Jung - [email protected]; Hans-Georg Rammensee - [email protected]; Steve Pascolo* - [email protected] * Corresponding author

Published: 29 May 2006 Genetic Vaccines and Therapy 2006, 4:4

doi:10.1186/1479-0556-4-4

Received: 28 February 2006 Accepted: 29 May 2006

This article is available from: http://www.gvt-journal.com/content/4/1/4 © 2006 Probst et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.

Background The presence of ribonucleases on human and rodent skin surfaces was described more than 40 years ago.[1,2] Subsequently their distribution within different skin layers was studied by different techniques.[3-5] However, the diversity, specificity and activity of extracellular (i.e. secreted or originating from dead cells) ribonucleases present on skin was never investigated. However, information is available on extracellular ribonucleases expressed in internal human organs.[6] These enzymes belong to the RNaseA protein su