Antisense therapeutics: from theory to clinical practice

Pharmacol Ther. 2003 Jul;99(1):55-77. doi: 10.1016/s0163-7258(03)00053-6.


The use of antisense (AS) oligonucleotides as therapeutic agents was proposed as far back as the 1960s/1970s when the AS strategy was initially developed. However, it has taken almost a quarter of a century for this potential to be realized. The last few years has seen a rapid increase in the number of AS molecules progressing past Phase I in clinical trials, due in part to our increased knowledge of their structure and chemistry. Here, we describe the most prominent of these modifications with respect to clinical applicability. However, the main focus of this review is clinical application, with a focus on cancer. We will discuss in detail both the status of the current AS clinical trials and the molecules that are likely to be the targets of the next group of AS molecules entering the clinic.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use*
  • Clinical Trials as Topic
  • Drug Delivery Systems
  • Drugs, Investigational
  • Gene Expression / drug effects
  • Humans
  • Molecular Structure
  • Oligonucleotides, Antisense / chemistry
  • Oligonucleotides, Antisense / pharmacology*
  • Oligonucleotides, Antisense / therapeutic use*
  • Structure-Activity Relationship


  • Antineoplastic Agents
  • Drugs, Investigational
  • Oligonucleotides, Antisense