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Towards Therapy Using RNA Interference

  • Targeted Therapeutics
  • Published:
American Journal of Pharmacogenomics

Abstract

Small interfering RNA (siRNA) molecules are short sequences of double-stranded RNA 19–27 bp in length, which suppress expression of target genes by inducing the breakdown of the cognate mRNA through mechanisms that are still being elucidated. siRNA molecules can be chemically synthesized or prepared through digestion of larger double-stranded RNA molecules using recombinant dicer or RNAase III enzyme. siRNA molecules can also be encoded by plasmid or virus vectors or expressed in transgenic animals. Design of siRNA sequences that efficiently suppress target genes can sometimes be challenging, although digestion of large double-standed RNA species with recombinant dicer or RNAase III may remove the necessity for testing multiple candidate siRNA. Exogenous siRNA can suppress translation for varying amounts of time depending on the half-life of the protein targeted. Vector-mediated approaches may improve duration but their use can be limited by the permanency and efficiency of transduction. Potential therapeutic targets for siRNA include viral and non-viral pathogens, cancer, neurodegenerative diseases, septic shock and macular degeneration. Suppression of expression via siRNA is also an extremely useful research tool for ascertaining gene function. Looking ahead to clinical applications, it will be important to know the consequences of inadvertent suppression of non-targeted sequences. If safety can be established, siRNA has the potential to significantly impact the field of molecular medicine.

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Acknowledgements

The authors thank Christine McLennan and Steven Eliason, from the University of Iowa, Department of Internal Medicine, for their assistance. This work was supported by NIH HD44093, The Hereditary Disease Foundation and the Roy J. Carver Trust (BLD).

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Authors and Affiliations

  1. Marshfield Clinic Research Foundation, Marshfield, Wisconsin, USA

    Joseph M. Alisky

  2. Marshfield Clinic-Thorp Center, Thorp, Wisconsin, USA

    Joseph M. Alisky

  3. Program in Gene Therapy, Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, Iowa, USA

    Beverly L. Davidson

  4. Department of Neurology, University of Iowa College of Medicine, Iowa City, Iowa, USA

    Beverly L. Davidson

  5. Department of Physiology & Biophysics, University of Iowa College of Medicine, Iowa City, 200 EMRB, Iowa, 52242, USA

    Beverly L. Davidson

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  1. Joseph M. Alisky
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  2. Beverly L. Davidson
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Correspondence to Beverly L. Davidson.

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Alisky, J.M., Davidson, B.L. Towards Therapy Using RNA Interference. Am J Pharmacogenomics 4, 45–51 (2004). https://doi.org/10.2165/00129785-200404010-00005

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  • DOI: https://doi.org/10.2165/00129785-200404010-00005

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