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A more recent version of this article appeared on October 1, 2007 Originally published online as doi:10.2353/ajpath.2007.070120 on August 23, 2007

Published online before print August 23, 2007
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Copyright © 2007 American Society for Investigative Pathology
American Journal of Pathology, doi:10.2353/ajpath.2007.070120

Accepted for publication May 31, 2007.

Article

Brothers in Arms. DNA Enzymes, Short Interfering RNA, and the Emerging Wave of Small-Molecule Nucleic Acid-Based Gene-Silencing Strategies

Ravinay Bhindi*{dagger}, Roger G. Fahmy*{dagger}, Harry C. Lowe*{dagger}, Colin N. Chesterman*{dagger}, Crispin R. Dass{ddagger}, Murray J. Cairns{sect}, Edward G. Saravolac, Lun-Quan Sun||, and Levon M. Khachigian*{dagger}@

From the Centre for Vascular Research,* Department of Pathology, School of Medical Sciences, The University of New South Wales, Sydney, New South Wales; Department of Haematology,{dagger} Prince of Wales Hospital, Sydney, New South Wales, Australia; Department of Orthopaedics,{ddagger} St. Vincent's Hospital Melbourne, Fitzroy, Victoria, Australia; Neuroscience Institute of Schizophrenia and Allied Disorders,{sect} School of Biomedical Sciences, University of Newcastle, Newcastle, New South Wales, Australia; Acrux Ltd., West Melbourne, Victoria, Australia; and Oligos Etc., Inc.,|| Wilsonville, Oregon

@ To whom correspondence should be addressed. E-mail: L.Khachigian{at}unsw.edu.au.


  Abstract

The past decade has seen the rapid evolution of small-molecule gene-silencing strategies, driven largely by enhanced understanding of gene function in the pathogenesis of disease. Over this time, many genes have been targeted by specifically engineered agents from different classes of nucleic acid-based drugs in experimental models of disease to probe, dissect, and characterize further the complex processes that underpin molecular signaling. Arising from this, a number of molecules have been examined in the setting of clinical trials, and several have recently made the successful transition from the bench to the clinic, heralding an exciting era of gene-specific treatments. This is particularly important because clear inadequacies in present therapies account for significant morbidity, mortality, and cost. The broad umbrella of gene-silencing therapeutics encompasses a range of agents that include DNA enzymes, short interfering RNA, antisense oligonucleotides, decoys, ribozymes, and aptamers. This review tracks current movements in these technologies, focusing mainly on DNA enzymes and short interfering RNA, because these are poised to play an integral role in antigene therapies in the future.






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Copyright © 2007 by the American Society for Investigative Pathology.