The development of small interfering RNA (siRNA) as antiviral against Avian Influenza Virus (AIV) infection

Posted by:
Risza Hartawan
41545858

The consequence of widely spread of AIV outbreaks subtype H5N1 in Asia, Africa and Europe has resulted on economic devastation at poultry industries as well as serious threat on public health circumstance. This segmented negative sense RNA virus from family Orthomyxovidae rapidly mutate via either antigenic drift or shift mechanism that have caused limitation of preexisting vaccines or antivirals. The discovery of siRNA activity as antiviral have furnished new perspective against the disease.
Several studies have dedicated to investigate the efficacy of siRNA, which targeted on AIV conserved genes to protect infection against AIV. Tompkins et al. (2004) designed siRNA specific for Nucleoprotein (NP) and Acidic Polymerase (PA) gene and employed oligofectamine as delivery system. By the intravenous (i.v.) administration before infection, they were successful to reduce mortality rate on the mice challenge study with several highly pathogenic strains of AIV (H1N1, H5N1, H7N7, and H9N2). Moreover, Zhou et al. (2007) was also successful to demonstrate inhibitory effect on the AIVs infection in vitro and in vitro using siRNA that targeted on Nucleoprotein (NP) and Matrix 2 (M2) gene using polyethylenimine (PEI) as carrier. Research by Zhou et al. (2008) using siRNA expression plasmids for NP, PA and PB1 gene also generated promising result. In addition, distinctive study was demonstrated by Ge et al. (2004), which administrated siRNA before and after infection. Using PEI as carrier with slow i.v. injection, the siRNA was able to decrease level of virus titer of challenging mice.
To sump up, the administration of siRNA that targeted on AIV conserved genes either before or after infection showed therapeutic effect against broad strain of AIVs. However, the utilization of these siRNAs were still incapable to induce sterile immune on the challenging animal. Moreover, subsequent researches have to be done to determine the best carrier to deliver siRNA into target cells.

Paper referred to:
1. Protection against lethal influenza virus challenge by RNA interference in vivo.
2. Inhibition of influenza virus production in virus-infected mice by RNA interference.
3. Effective small interfering RNAs targeting matrix and nucleocapsid protein gene inhibit influenza A virus replication in cells and mice.
4. RNA interference of avian influenza virus H5N1 by inhibiting viral mRNA with siRNA expression plasmids.