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Gene silencing in the therapy of influenza and other respiratory diseases: Targeting to RNase P by use of External Guide Sequences (EGS)

Authors David H Dreyfus, S Mark Tompkins, Ramsay Fuleihan, Lucy Y Ghoda

Published 15 February 2008 Volume 2007:1(4) Pages 425—432

David H Dreyfus1,2, S Mark Tompkins3, Ramsay Fuleihan1, Lucy Y Ghoda2,4

1Department of Pediatrics, Yale University School of Medicine, New Haven, CT, USA; 2Keren Pharmaceuticals, New Haven, CT, USA; 3Department of Infectious Diseases, University of Georgia College of Veterinary Medicine, Athens, GA, USA; 4The Webb-Waring Institute and the Department of Medicine, University of Colorado Health Sciences Center, Denver, CO

Abstract: Respiratory diseases provide an attractive target for gene silencing using small nucleic acids since the respiratory epithelium can be reached by inhalation therapy. Natural surfactant appears to facilitate the uptake and distribution of these types of molecules making aerosolized nucleic acids a possible new class of therapeutics. This article will review the rationale for the use of External Guide Sequence (EGS) in targeting specific mRNA molecules for RNase P-mediated intracellular destruction. Specific destruction of target mRNA results in gene-specific silencing similar to that instigated by siRNA via the RISC complex. The application of EGS molecules specific for influenza genes are discussed as well as the potential for synergy with siRNA. Furthermore, EGS could be adapted to target other respiratory diseases of viral etiology as well as conditions such as asthma.

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