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Design and Selection of Antisense Oligonucleotides Targeting Transforming Growth Factor Beta (TGF-β) Isoform mRNAs for the Treatment of Solid Tumors

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Gene Therapy of Solid Cancers

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1317))

Abstract

Transforming growth factor beta isoforms (TGF-β1, -β2, and -β3) are cytokines associated with a wide range of biological processes in oncology including tumor cell invasion and migration, angiogenesis, immunosuppression, as well as regulation of tumor stem cell properties. Hence, blocking the TGF-β signaling pathways may have a multifold therapeutic benefit for the treatment of solid tumors. Here, we describe the identification and selection processes for the development of highly potent and selective chemically modified antisense oligodeoxynucleotides (fully phosphorothioate locked nucleic acid gapmers) allowing effective and selective suppression of TGF-β isoform expression in cell-based assays and in vivo preclinical models.

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Acknowledgement

The authors wish to acknowledge and recognize superb technical and scientific support from Marcus Kielmanowicz, Axolabs GmbH (Kulmbach, Germany), and Oncodesign (Dijon, France).

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Correspondence to Michel Janicot .

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Jaschinski, F., Korhonen, H., Janicot, M. (2015). Design and Selection of Antisense Oligonucleotides Targeting Transforming Growth Factor Beta (TGF-β) Isoform mRNAs for the Treatment of Solid Tumors. In: Walther, W., Stein, U. (eds) Gene Therapy of Solid Cancers. Methods in Molecular Biology, vol 1317. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-2727-2_9

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  • DOI: https://doi.org/10.1007/978-1-4939-2727-2_9

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-2726-5

  • Online ISBN: 978-1-4939-2727-2

  • eBook Packages: Springer Protocols

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