Sensitivity to siRNA

Small interfering RNAs (siRNA) are short double-stranded RNAs of about 21 base pairs. They have offered great promise as ways to interfere with virus replication and therapies in humans are already underway. Many RNA viruses have been tested and found susceptible to siRNA attack (Bitko and Barik 2001; Coburn and Cullen 2002; Ge et al. 2003; Gitlin et al. 2002). Consistent with this, the replication of HDV in cultured cells can be inhibited by transfection of appropriate siRNA species (Chang and Taylor 2003). A caveat here is that only siRNA targeted against the HDV mRNA produce such inhibition. Those targeted against other regions on the genome or antigenome do not block replication. One possible reason for resistance is that the genomic and antige-nomic RNAs are located in the nucleus, away from the RISC complex that is considered to mediate siRNA action. Another possibility is that the binding of S-HDAg to these RNAs confers resistance to siRNA-mediated degradation.

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