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Inhibition of Gene Expression by Nucleic Acid Enzymes in Rodent Models of Human Disease

  • Per Ole Iversen
  • Mouldy Sioud
Part of the Methods in Molecular Biology™ book series (MIMB, volume 252)

Abstract

Nucleic acid enzymes have emerged as a versatile technique for sequence-specific gene silencing in a wide range of cells. However, the question remains as to whether, for example, DNA enzymes and ribozymes are functional in animals. In this chapter, we describe two different rodent models of human diseases—namely, leukemia and chronic heart failure. We specifically reduced Raf-1 expression in leukemic mice using an anti-Raf-1 DNA enzyme. A continuous supply of this catalytic molecule led to a substantial reduction in leukemic-cell burden and survival. Rats with postinfarction heart failure were treated with a DNA enzyme targeting TNFa, and this led to a substantial improvement of cardiac function concomitant with a restoration of the hemodynamic status of the animals. The described protocols should facilitate the in vivo evaluation of other oligonucleotide-based therapy such as small interferering RNAs (siRNAs).

Keywords

Left Coronary Artery Cationic Liposome Childhood Leukemia Left Ventricular Myocardium Osmotic Minipump 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Humana Press Inc., Totowa, NJ 2004

Authors and Affiliations

  • Per Ole Iversen
    • 1
  • Mouldy Sioud
    • 2
  1. 1.Institute for NutritionUniversity of OsloOsloNorway
  2. 2.Department of Immunology, Molecular Medicine GroupThe Norwegian Radium HospitalOsloNorway

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