Recent progress in oligonucleotide therapeutics: antisense to aptamers

Abstract

Background: Antisense and other RNA-targeting strategies have the potential to impact a broad array of human diseases. Although the methodological approaches for achieving targeted RNA degradation have changed over the past 5 – 10 years, the technological hurdles facing these and other nucleic acid-based drugs have remained fairly constant. Objective: To provide an update on the clinical status of several antisense compounds and discuss methodological strategies for improving efficacy of antisense compounds and other nucleic acid therapeutics. Method: Some of the clinical advances in antisense therapeutics, including a description of sugar or backbone modifications and delivery approaches for improving antisense efficacy are highlighted; a few alternative nucleic acid strategies are discussed. Conclusion: Although a variety of technological issues continue to hamper antisense progress towards the clinic, advances in stabilization and delivery have provided new hope for using nucleic acids as drugs.

Keywords::

• adjuvants
• antisense oligodeoxynucleotides
• aptamers
• cell penetrating peptides

Acknowledgements

The author thanks past colleagues, particularly Drs Hagen Cramer, Paul Torrence, Bryan Williams and Bob Silverman, for insightful discussions about the prospects of applying antisense technology to human medical conditions.