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A tumor specific single chain antibody dependent gene expression system

Oncogene volume 18, pages 559–564 (1999)Cite this article

Abstract

The design of conditional gene expression systems restricted to given tissues or cellular types is an important issue of gene therapy. Systems based on the targeting of molecules characteristic of the pathological state of tissues would be of interest. We have developed a synthetic transcription factor by fusing a single chain antibody (scFv) directed against p53 with the bacterial tetracycline repressor as a DNA binding domain. This hybrid protein binds to p53 and can interact with a synthetic promoter containing tetracycline-operator sequences. Gene expression can now be specifically achieved in tumor cells harboring an endogenous mutant p53 but not in a wild-type p53 containing tumor cell line or in a non-transformed cell line. Thus, a functional transactivator centered on single chain antibodies can be expressed intracellularly and induce gene expression in a scFv-mediated specific manner. This novel class of transcriptional transactivators could be referred as `trabodies' for transcription-activating-antibodies. The trabodies technology could be useful to any cell type in which a disease related protein could be the target of specific antibodies.

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Acknowledgements

This work was supported by the BioAvenir Programme (MENESR)

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Authors and Affiliations

  1. Gene Medicine Department, Rhóne-Poulenc Rorer S.A, 13 quai Jules Guesde, 94403, Vitry-sur-Seine, France

    Marie-Noëlle Mary, Corinne Venot, Claude Caron de Fromentel, Laurent Debussche, Emmanuel Conseiller, Fabien Schweighoffer, Bruno Tocque & Laurent Bracco

  2. Laboratoire de Biotechnologie des Anticorps, France

    Olivier Cochet, Nadège Gruel & Jean-Luc Teillaud

  3. Institut Curie, Unité INSERM 255, 26 rue d'Ulm, 75005, Paris, France

    Jean-Luc Teillaud

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  1. Marie-Noëlle Mary
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  2. Corinne Venot
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Mary, MN., Venot, C., Caron de Fromentel, C. et al. A tumor specific single chain antibody dependent gene expression system. Oncogene 18, 559–564 (1999). https://doi.org/10.1038/sj.onc.1202377

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