Development of antiviral LNA gapmers targeting functional stem-loop structures in tick-borne flavivirus genomes
Year: 2026
Type: article
Abstract: Antisense oligonucleotide gapmers degrade target RNA in a sequence-specific and RNase H-dependent manner and are emerging as a promising antiviral strategy. Locked nucleic acid-modified gapmers have shown activity against several pathogenic viruses. Tick-borne encephalitis virus is widely distributed across Eurasia, with approximately 10,000 cases reported annually, and the absence of approved therapies represents a significant public health concern. In this study, we designed 71 locked nucleic acid-modified gapmers targeting structural elements within the untranslated regions of the single-stranded positive-sense RNA genome of tick-borne encephalitis virus. The antiviral efficacy of gapmers selected via in silico analysis was evaluated using a replicon system and infectious virus assays. Gapmers targeting stem-loop structures in the 3′ untranslated region effectively inhibited viral replication. Optimizing the length and composition of the lead gapmers further enhanced antiviral potency. Sequence alignment analysis revealed that the target regions of the optimized gapmers were highly conserved among the three major subtypes of tick-borne encephalitis virus. Accordingly, the optimized gapmers markedly inhibited replication of a highly pathogenic strain, suggesting broad-spectrum activity. Collectively, our findings support the development of locked nucleic acid-modified gapmers as therapeutics against tick-borne encephalitis virus and other tick-borne flaviviruses.
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,900
OpenAlex ID: W7222239724