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Oligonucleotides

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Pharmaceutical Biotechnology

Abstract

Oligonucleotides are short chains of single stranded or double stranded nucleotides, either DNA, RNA or a combination and in some cases chemically modified to improve their application as a drug substance. They are applied to modulate endogenous mechanisms of DNA and RNA processing, thereby modifying disease pathways at the genetic level, rather than at the protein level like conventional drugs. Factors that limit the application of oligonucleotide drugs are immunogenicity, instability and poor pharmacokinetics. In this chapter, several mechanisms are described of how oligonucleotides can act as drugs, as well as several approaches to overcome the limitations that are inherent to this drug class. A recent advancement is the formulation of oligonucleotides in lipid nanoparticles, an approach that has proven to be successful and has led to the first marketed siRNA drug.

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Author information

Authors and Affiliations

  1. Laboratory Clinical Chemistry & Haematology, University Medical Center Utrecht, Utrecht, The Netherlands

    Raymond M. Schiffelers

  2. Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands

    Erik Oude Blenke

  3. Department of Pharmaceutics, Utrecht University, Utrecht, The Netherlands

    Enrico Mastrobattista

Authors
  1. Raymond M. Schiffelers
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  2. Erik Oude Blenke
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  3. Enrico Mastrobattista
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Corresponding author

Correspondence to Raymond M. Schiffelers .

Editor information

Editors and Affiliations

  1. Utrecht University, Utrecht, The Netherlands

    Daan J. A. Crommelin

  2. Faculty of Pharmaceutical Sciences and The Centre for Health Evaluation & Outcomes Sciences (CHEOS), The University of British Columbia (UBC), Vancouver, BC, Canada

    Robert D. Sindelar

  3. College of Pharmacy, University of Tennessee, Health Science Center, Memphis, TN, USA

    Bernd Meibohm

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Schiffelers, R.M., Blenke, E.O., Mastrobattista, E. (2019). Oligonucleotides. In: Crommelin, D., Sindelar, R., Meibohm, B. (eds) Pharmaceutical Biotechnology. Springer, Cham. https://doi.org/10.1007/978-3-030-00710-2_15

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