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Delivery of Phosphorodiamidate Morpholino Antisense Oligomers in Cancer Cells

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Gene Therapy of Cancer

Part of the book series: Methods in Molecular Biology™ ((MIMB,volume 542))

Summary

Phosphorodiamidate morpholino oligomers (PMO), which have a neutral chemistry, are extensively being used as tools for selective inhibition of gene expression in cell culture models and are currently in human clinical trials. PMO oligomers possess a unique structure, in which the deoxyribose moiety of DNA is replaced with a six-membered morpholine ring and the charged phosphodiester internucleoside linkages are replaced with neutral phosphorodiamidate linkages. PMO internalization in uptake-permissive cells has been observed to be specific, saturable, and energy-dependent, suggesting a receptor-mediated uptake mechanism. Understanding PMO transport should facilitate the design of more effective synthetic antisense oligomers as therapeutic agents.

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Acknowledgments

I thank Katherine Aird and Rami Ghanayem for editorial and technical assistance and Dr. Patrick Iversen (Avi BioPharma Inc.). Some of the work presented here was supported by Department of Defense (DOD) grants DAMD17-01-1-0017 (GRD) and W81XWH-07-1-0392 (GRD).

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Authors and Affiliations

  1. Department of Surgery and Duke Comprehensive Cancer Ctr, Box 2606, Duke University Medical Center, Durham, NC, 27710, USA

    Gayathri R. Devi

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  1. Gayathri R. Devi
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Correspondence to Gayathri R. Devi .

Editor information

Editors and Affiliations

  1. Molecular Medicine (MDC), Max Delbrück Center for, Robert-Rössle-Str. 10, Berlin, 13125, Germany

    Wolfgang Walther

  2. Molecular Medicine (MDC), Max Delbrück Center for, Robert-Rössle-Str. 10, Berlin, 13125, Germany

    Ulrike S. Stein

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© 2009 Humana Press, a part of Springer Science+Business Media, LLC

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Devi, G.R. (2009). Delivery of Phosphorodiamidate Morpholino Antisense Oligomers in Cancer Cells. In: Walther, W., Stein, U. (eds) Gene Therapy of Cancer. Methods in Molecular Biology™, vol 542. Humana Press. https://doi.org/10.1007/978-1-59745-561-9_19

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  • DOI: https://doi.org/10.1007/978-1-59745-561-9_19

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  • Publisher Name: Humana Press

  • Print ISBN: 978-1-934115-85-5

  • Online ISBN: 978-1-59745-561-9

  • eBook Packages: Springer Protocols

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