Abstract
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.