Prophylactic and Therapeutic Effects of Small Interfering Rna Targeting Sars-Coronavirus
2004; SAGE Publishing; Volume: 9; Issue: 3 Linguagem: Inglês
10.1177/135965350400900310
ISSN2040-2058
AutoresBo‐Jian Zheng, Yi Guan, Qingquan Tang, Du Cheng, Frank Xie, Ming‐Liang He, Kwok-Wah Chan, Kin‐Ling Wong, Eric Lader, Martin C. Woodle, Patrick Lu, Baojian Li, Nanshan Zhong,
Tópico(s)Advanced biosensing and bioanalysis techniques
ResumoTo identify and characterize the siRNA duplexes that are effective for inhibition of SARS-CoV infection and replication in the non-human primate cells. This in vitro study will serve as the foundation for development of novel anti-SARS therapeutics.48 siRNA sequences were designed for targeting regions throughout entire SARS-CoV genome RNA including open-reading frames for several key proteins. Chemically synthesized siRNA duplexes were transfected into foetal rhesus kidney (FRhK-4) cells prior to or after SARS-CoV infection. The inhibitory effects of the siRNAs were evaluated for reductions of intracellular viral genome copy number and viral titres in the cell culture medium measured by Q-RT-PCR and CPE-based titration, respectively. Four siRNA duplexes were found to achieve potent inhibition of SARS-CoV infection and replication. A prolonged prophylactic effect of siRNA duplexes with up to 90% inhibition that lasted for at least 72 h was observed. Combination of active siRNA duplexes targeting different regions of the viral genome resulted in therapeutic activity of up to 80% inhibition.Chemically synthesized siRNA duplexes targeting SARS-CoV genomic RNA are potent agents for inhibition of the viral infection and replication. The location effects of siRNAs were revealed at both genome sequence and open-reading frame levels. The rapid development of siRNA-based SARS-CoV inhibitors marked a novel approach for combating newly emergent infectious diseases.
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