Hong Kong Med J 2009;15(Suppl 4):S28-31
Development of interfering RNA agents to inhibit SARS-associated coronavirus infection and replication
ML He, BJ Zheng, Y Chen, KL Wong, JD Huang, MC Lin, KY Yuen, JJY Sung, HF Kung
Stanley Ho Centre for Emerging Infectious Diseases, The Chinese University of Hong Kong
1. Small interfering RNAs (siRNAs) were designed to knock-down the four structural genes in severe acute respiratory syndrome–associated coronavirus (SCoV). Antiviral effects were confirmed by reduction of viral cytopathic effects and reduction in viral genomic RNA.
2. The siRNAs inhibited SCoV in a dose-dependent manner and had half-lives of approximately 24 hours.
3. The siRNAs acted synergistically with each other at low doses to enhance inhibition of SCoV. Specific siRNAs acted synergistically with interferon-_ to massively (~100 000-fold) inhibit SCoV replication, compared to controls.
4. Recombinant adenovirus–based vectors expressing short hairpin RNA molecules were developed that potently inhibited SCoV replication and virus production.