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In Vitro Cellular Uptake, Distribution, and Metabolism of Oligonucleotides

  • Chapter
Antisense Research and Application

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 131))

Abstract

Eighteen years ago, Zamecnik and Stephenson used synthetic antisense oligonucleotides to inhibit Rous sarcoma virus replication and RNA translation in a cellular system ([Zamecnix and Stephenson 1978]). Since that time, enormous progress has been made towards the development of antisense oligo-nucleotides as therapeutic agents against a wide variety of host and viral disease targets ([Crooke and Lebleu 1993]; [St Crooke 1995a]; [Crooke and Bennett 1996]). Like other pharmacological agents, these novel compounds have both specific and nonspecific effects ([Stein and Cheng 1993]; [Crooke and Bennett 1996]; [ST Crooke 1996]). However, constantly emerging data from properly performed and appropriately controlled in vitro and in vivo experiments, as well as preliminary clinical data, suggest that antisense therapeutics do work via an antisense mechanism, i.e., by altering intermediary RNA metabolism and ultimately decreasing production of disease-associated gene products ([Crooke and Bennett 1996]; [Crooke 1996]).

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Authors
  1. R. M. Crooke
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  1. ISIS Pharmaceuticals, Inc., Carlsbad Research Center, 2292 Faraday Avenue, Carlsbad, CA, 92008, USA

    Stanley T. Crooke M.D., Ph.D.

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© 1998 Springer-Verlag Berlin Heidelberg

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Crooke, R.M. (1998). In Vitro Cellular Uptake, Distribution, and Metabolism of Oligonucleotides. In: Crooke, S.T. (eds) Antisense Research and Application. Handbook of Experimental Pharmacology, vol 131. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-58785-6_3

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  • DOI: https://doi.org/10.1007/978-3-642-58785-6_3

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