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Receptor-Dependent Cell Specific Delivery of Antisense Oligonucleotides

  • Chapter
Cardiovascular Specific Gene Expression

Part of the book series: Developments in Cardiovascular Medicine ((DICM,volume 214))

Abstract

Oligodeoxynucleotides (ODNs) have been shown to inhibit gene expression at various levels both in vitro and in vivo [1–4]. In vivo, the efficacy of ODN-induced regulation of genes in specific cell types may be suboptimal due to poor accumulation of ODNs in these cells. In addition, untimely elimination of ODNs via renal clearance, degradation and scavenger receptor-mediated uptake [6] may further impair their therapeutic activity. These hurdles can be at least partly overcome by targeted delivery of the ODNs to the desired site of action. A number of approaches have been suggested to facilitate the entry of polyanionic ODNs into the aimed target cell [7–12]. Neutral and cationic liposomes are considered to be attractive ODN carriers since they markedly enhance cellular uptake under in vitro conditions. Like native ODNs, however, liposomally formulated ODNs are mainly captured by cells of the reticulo-endothelial system in lungs, spleen and liver [13–15], as a result of which the ODN concentration in the target cell will be suboptimal. After local delivery of ODNs encapsulated in virus capsid-coated liposomes, Morishita et al. [16] could enhance ODN uptake by vascular endothelial cells leading to cell-specific antisense effects. Nevertheless, this approach is not feasible for specific delivery of ODNs to most other cell types like the parenchymal liver cell (PC).

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Authors
  1. Erik A. L. Biessen
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  2. Theo J. C. van Berkel
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Editor information

Editors and Affiliations

  1. Department of Cardiology, Academic Hospital Maastricht, Maastricht, The Netherlands

    Pieter A. Doevendans

  2. Academic Hospital Maastricht, CARIM, Maastricht, The Netherlands

    Robert S. Reneman

  3. Department of Physiology, Academic Hospital Maastricht, Maastricht, The Netherlands

    Marc van Bilsen

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© 1999 Springer Science+Business Media Dordrecht

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Biessen, E.A.L., van Berkel, T.J.C. (1999). Receptor-Dependent Cell Specific Delivery of Antisense Oligonucleotides. In: Doevendans, P.A., Reneman, R.S., van Bilsen, M. (eds) Cardiovascular Specific Gene Expression. Developments in Cardiovascular Medicine, vol 214. Springer, Dordrecht. https://doi.org/10.1007/978-94-015-9321-2_24

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  • DOI: https://doi.org/10.1007/978-94-015-9321-2_24

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-90-481-5189-9

  • Online ISBN: 978-94-015-9321-2

  • eBook Packages: Springer Book Archive

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