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Journal of Virology, February 2008, p. 1610-1614, Vol. 82, No. 3
0022-538X/08/$08.00+0     doi:10.1128/JVI.01734-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Transgene Expression Facilitated by the v-src Splice Acceptor Can Impair Replication Kinetics and Lead to Genomic Instability of Rous Sarcoma Virus-Based Vectors{triangledown} ,{dagger}

Daniel Portsmouth,1,2 Daria Deitermann,1 Brian Salmons,3 Walter H. Günzburg,1,2 and Matthias Renner3*

Research Institute of Virology and Biomedicine, University of Veterinary Medicine,1 Christian-Doppler Laboratory for Gene Therapeutic Vector Development,2 Austrianova Biotechnology GmbH, Vienna, Austria3

Received 9 August 2007/ Accepted 19 November 2007

Rous sarcoma virus (RSV) can be used for the simple generation of high-titer replication-competent retroviral (RCR) vectors. Retroviruses undergo frequent genomic recombination, however, and vectors with reduced replication kinetics are rapidly overgrown by mutant forms. Vector design is hence critical to vector efficacy. In this study, two different designs of RSV-based RCR vectors were evaluated. Vectors in which transgene expression was facilitated by the v-src splice acceptor were revealed to have greatly reduced replication kinetics and genomic stability in comparison to vectors in which transgene expression was mediated by an internal ribosome entry site in the 3' untranslated region.

* Corresponding author. Mailing address: MR, Austrianova Biomanufacturing AG, Veterinaerplatz 1, A-1210 Vienna, Austria. Phone: 43-1-25077-2301. Fax: 43-1-25077-2390. E-mail: renner{at}austrianova.com

{triangledown} Published ahead of print on 5 December 2007.

{dagger} Supplemental material for this article may be found at http://jvi.asm.org/.

Journal of Virology, February 2008, p. 1610-1614, Vol. 82, No. 3
0022-538X/08/$08.00+0     doi:10.1128/JVI.01734-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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