A chimeric RNA consisting of siRNA and aptamer for inhibiting dengue virus replication

Silencing viruses by chimeric RNAs, wherein small interfering RNAs (siRNAs) targeting viral RNAs are conjugated with RNA aptamers specific to viral envelope proteins, is a promising treatment for viral infection diseases; however, practical evaluations are apparently lacking. Here, we present a chimeric RNA comprises siRNA and RNA aptamer, both of which target all four serotypes of dengue virus (DENV), for suppressing DENV replication. The siRNA targeting consensus sequences in the 3'-UTR of all four DENV serotypes suppressed the expression of a reporter gene carrying the siRNA-targeted sequence of DENV-1 by ∼70%. The RNA aptamer generated by VLP-SELEX using DENV-1-VLPs as baits showed an affinity for all four DENV-VLP serotypes, presumably without affecting the fusion process. After conjugation of each modality, the chimeric RNA significantly suppressed authentic DENV-1 and DENV-2 production in vitro. Our study provides evidence that chimeric RNA is a potentially effective antiviral agent.