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The Dengue virus (DENV) RNA is a single-stranded, positive-sense molecule of approximately 11 kilobases that serves as the primary genetic material and the template for protein synthesis during infection (PMID: 21170310). It contains a single open reading frame encoding a polyprotein that is subsequently processed into three structural and seven non-structural proteins, including the RNA-dependent RNA polymerase NS5 (PMID: 15650191). The RNA is characterized by highly conserved 5' and 3' untranslated regions (UTRs) that form complex secondary and tertiary structures essential for viral genome circularization, replication, and evasion of the host innate immune response (PMID: 21502333). As a therapeutic target, DENV RNA is the focus of nucleic acid-based strategies such as antisense oligonucleotides (ASOs), phosphorodiamidate morpholino oligomers (PMOs), and small interfering RNAs (siRNAs) (PMID: 15650191). These modalities aim to achieve sequence-specific inhibition of viral translation or induce degradation of the viral genome, potentially offering a pan-serotype approach if targeting conserved regions (PMID: 21502333). Despite its potential, no RNA-targeted therapies are currently approved, with development facing hurdles such as the high mutation rate of the virus and the challenge of delivering oligonucleotides to infected monocytes and macrophages.
Antisense inhibition of viral translation and replication through sequence-specific binding to viral RNA, or RNA interference-mediated degradation of the viral genome.
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