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Toward RNA interference‐based therapy for filovirus infections
Author(s) -
Spurgers Kevin B.,
Silvestri Lynn S.,
Warfield Kelly L.,
Bavari Sina
Publication year - 2009
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.20302
Subject(s) - small interfering rna , rna interference , filoviridae , virology , rna , biology , ebola virus , marburg virus , medicine , virus , viral disease , genetics , gene , paramyxoviridae
Ebola (EBOV) and Marburg (MARV) viruses, of the family filoviridae, cause severe hemorrhagic fever in humans and nonhuman primates (NHPs) with mortality rates of up to 90%. Infection is thought to occur through mucous membranes or breaks in the skin after contact with infected animal tissue or body fluids of infected individuals. Beyond naturally occurring outbreaks, the potential use of these viruses in acts of bioterrorism remains a public health and national security concern. EBOV and MARV are classified as category A bioterrorism agents by the Centers for Disease Control and Prevention (CDC). To date, there are no licensed vaccines or therapeutics for filovirus infections. Major efforts are now under way to develop anti‐viral therapeutics that use the cellular RNA interference (RNAi) pathway. Small synthetic double‐stranded RNA oligonucleotides (siRNAs), or small hairpin RNAs (shRNAs) enter the RNAi pathway and guide the degradation of target mRNA transcripts with homologous sequence, for experimental or therapeutic benefit. Chemical modifications improve the in vivo stability of siRNAs and various strategies are being investigated to improve delivery. Importantly, siRNAs and shRNAs have been successfully used to inhibit virus replication in vitro, and in animal models. siRNAs as therapy for a variety of ailments have now moved into clinical trials. This review provides an overview of therapeutic siRNAs and details preclinical efforts to use these molecules as therapy for filovirus infections. Drug Dev Res 70:246–254, 2009. Published 2009 Wiley‐Liss, Inc.