A Status Update of Modified Oligonucleotides for Chemotherapeutics Applications

Yogesh S. Sanghvi1

1 Rasayan Inc., Encinitas, California
Publication Name:  Current Protocols in Nucleic Acid Chemistry
Unit Number:  Unit 4.1
DOI:  10.1002/0471142700.nc0401s46
Online Posting Date:  September, 2011
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This unit presents an update of recent developments and clinical progress in chemically modified oliogonucleotides useful for therapeutic applications. During the last decade, the number of therapeutic oligonucleotides in clinical trials has nearly tripled. This is primarily due to advances in the synthesis protocols, better understanding of the biology, improved delivery, and better formulation technologies. Currently, over 100 clinical trials with oligonucleotide‐based drugs are ongoing in the United States for potential treatment of a variety of life‐threatening diseases. Among various oligonucleotides, antisense technology has been at the forefront, with one product on the market. Antisense technologies represent about half of the active clinical trials. Similarly, siRNA, aptamers, spiegelmers microRNA, shRNA, IMO, and CpG have been other active classes of oligonucleotides that are also undergoing clinical trials. This review attempts to summarize the current status of synthesis, chemical modifications, purification, and analysis in light of the rapid progress with multitude of oligonucleotides pursued as therapeutic modality. Curr. Protoc. Nucleic Acid Chem. 46:4.1.1‐4.1.22. © 2011 by John Wiley & Sons, Inc.

Keywords: antisense; aptamers; microRNA; shRNA; siRNA; RNAi; oligonucleotides

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Table of Contents

  • Introduction
  • Overview of Manufacturing Process
  • Chemical Modifications in Oligonucleotides
  • Strategies for Optimizing Therapeutic Potential of Oligonucleotide‐Based Drugs
  • Future Outlook
  • Literature Cited
  • Figures
  • Tables
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Literature Cited

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