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The Approach of Triple Helix Formation in Control of Gene Expression and The Treatment of Tumors Expressing IGF-I

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Cancer Gene Therapy

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 465))

Conclusion

The triplex-based strategy as the well-known antisense strategy seems to be a pow-erful approach to control gene expression in malignant cells. Few examples of the inhibitory activity of triplex-forming oligonucleotides on target genes involved in tumori-genesis are now available (for reviews see (Chan and Glazer, 1997; Giovannangeli and Hélène, 1997; Maher III, 1996; Vasquez and Wilson, 1998)). Most of the TFOs are tar-geted to polypurine-polypyrimidine sequences located in control regions of the gene of interest and are cell delivered via transaction with various chemical carriers. An alternative way to introduce TFOs in cells is to use a plasmid vector that can drive the synthesis of an RNA triplex-forming oligonucleotide inside the cells. This TFO generated in situ is therefore protected from degradation by nucleases and could reach its DNA target without being trapped in lysosomal vesicles. Obviously, it could be trans-fected in cells via either standard cell transfection procedures or via ways similarly used in virus-based gene therapy. An application of this triplex-based approach has been used for the inhibition of the Insulin-like growth factor I protein which plays a major role in tumorigenesis of glioblastoma and hepatocarcinoma (Shevelev et al., 1997; Upegui-Gonzalez et al., 1998b). The inhibition of IGF-I using antisense or triple-helix tech-nologies in these cells induced an immune response of syngenic animals (Lafarge-Frayssinet et al., 1997; Shevelev et al., 1997; Trojan et al., 1993; Upegui-Gonzalez et al., 1998a; Upegui-Gonzalez et al., 1998b). These results obtained with IGF-I familly may ultimately lead to the use of the antisense and triplex-based approaches in clinical trials for anticancer gene therapy.

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Authors and Affiliations

  1. Laboratoire de Biophysique INSERM U201, CNRS UA481, Museum National d’Histoire Naturelle, 43 rue Cuvier, 75231, Paris Cedex 05, France

    Jean-Christophe François

  2. Laboratoire de Neurologie du Developpement, INSERM-CRI 9701, 48 bd Serurier, 75019, Paris, France

    Adama Ly & Jerzy Trojan

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  1. Lia C. Upegui-Gonzalez
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  2. Jean-Christophe François
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  3. Adama Ly
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  4. Jerzy Trojan
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  1. Imperial College School of Medicine, Hammersmith Hospital, London, UK

    Nagy A. Habib

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Upegui-Gonzalez, L.C., François, JC., Ly, A., Trojan, J. (2002). The Approach of Triple Helix Formation in Control of Gene Expression and The Treatment of Tumors Expressing IGF-I. In: Habib, N.A. (eds) Cancer Gene Therapy. Advances in Experimental Medicine and Biology, vol 465. Springer, New York, NY. https://doi.org/10.1007/0-306-46817-4_27

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