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Journal of Virology, July 2007, p. 6973-6983, Vol. 81, No. 13
0022-538X/07/$08.00+0     doi:10.1128/JVI.02470-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Effects of Viral Strain, Transgene Position, and Target Cell Type on Replication Kinetics, Genomic Stability, and Transgene Expression of Replication-Competent Murine Leukemia Virus-Based Vectors{triangledown}

Matthias Paar,1,2 Sonja Schwab,1 Doris Rosenfellner,1 Brian Salmons,3 Walter H. Günzburg,1,2 Matthias Renner,3* and Daniel Portsmouth1,2

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

Received 9 November 2006/ Accepted 5 April 2007

The limited efficiency of in vivo gene transfer by replication-deficient retroviral vectors remains an obstacle to achieving effective gene therapy for solid tumors. One approach to circumvent this problem is the use of replication-competent retroviral vectors. However, the application of such vectors is at a comparatively early stage and the effects which virus strain, transgene cassette position, and target cell can exert on vector spread kinetics, genomic stability, and transgene expression levels remain to be fully elucidated. Thus, in this study a panel of vectors allowing the investigation of different design features on an otherwise genetically identical background were analyzed with respect to these readout parameters in cultures of both murine and human cells and in preformed tumors in nude mice. The obtained data revealed that (i) Moloney murine leukemia virus (Mo-MLV)-based vectors spread with faster kinetics, drive higher levels of transgene expression, and are more stable than equivalent Akv-MLV-based vectors; (ii) vectors containing the transgene cassette directly downstream of the envelope gene are genomically more stable than those containing it within the 3'-long terminal repeat U3 region; and (iii) the genomic stability of both strains seems to be cell line dependent.

* Corresponding author. Mailing address: Austrianova Biotechnology GmbH, 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 18 April 2007.

Journal of Virology, July 2007, p. 6973-6983, Vol. 81, No. 13
0022-538X/07/$08.00+0     doi:10.1128/JVI.02470-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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