{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T22:06:04Z","timestamp":1790805964374,"version":"4.1.0"},"reference-count":63,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2023,10,2]],"date-time":"2023-10-02T00:00:00Z","timestamp":1696204800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Japan Science Society the Sasakawa Scientific Research","award":["2022-4048"],"award-info":[{"award-number":["2022-4048"]}]},{"name":"Japan Science Society the Sasakawa Scientific Research","award":["17H07142"],"award-info":[{"award-number":["17H07142"]}]},{"name":"Japan Science Society the Sasakawa Scientific Research","award":["18K14595"],"award-info":[{"award-number":["18K14595"]}]},{"name":"Japan Science Society the Sasakawa Scientific Research","award":["H29No.8"],"award-info":[{"award-number":["H29No.8"]}]},{"name":"JSPS KAKENHI","award":["2022-4048"],"award-info":[{"award-number":["2022-4048"]}]},{"name":"JSPS KAKENHI","award":["17H07142"],"award-info":[{"award-number":["17H07142"]}]},{"name":"JSPS KAKENHI","award":["18K14595"],"award-info":[{"award-number":["18K14595"]}]},{"name":"JSPS KAKENHI","award":["H29No.8"],"award-info":[{"award-number":["H29No.8"]}]},{"name":"Nihon University","award":["2022-4048"],"award-info":[{"award-number":["2022-4048"]}]},{"name":"Nihon University","award":["17H07142"],"award-info":[{"award-number":["17H07142"]}]},{"name":"Nihon University","award":["18K14595"],"award-info":[{"award-number":["18K14595"]}]},{"name":"Nihon University","award":["H29No.8"],"award-info":[{"award-number":["H29No.8"]}]},{"DOI":"10.13039\/501100003806","name":"HOKUTO Foundation for Bioscience","doi-asserted-by":"publisher","award":["2022-4048"],"award-info":[{"award-number":["2022-4048"]}],"id":[{"id":"10.13039\/501100003806","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003806","name":"HOKUTO Foundation for Bioscience","doi-asserted-by":"publisher","award":["17H07142"],"award-info":[{"award-number":["17H07142"]}],"id":[{"id":"10.13039\/501100003806","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003806","name":"HOKUTO Foundation for Bioscience","doi-asserted-by":"publisher","award":["18K14595"],"award-info":[{"award-number":["18K14595"]}],"id":[{"id":"10.13039\/501100003806","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003806","name":"HOKUTO Foundation for Bioscience","doi-asserted-by":"publisher","award":["H29No.8"],"award-info":[{"award-number":["H29No.8"]}],"id":[{"id":"10.13039\/501100003806","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>RNase H-dependent gapmer antisense oligonucleotides (ASOs) are a promising therapeutic approach via sequence-specific binding to and degrading target RNAs. However, the efficacy and mechanism of antiviral gapmer ASOs have remained unclear. Here, we investigated the inhibitory effects of gapmer ASOs containing locked nucleic acids (LNA gapmers) on proliferating a mosquito-borne flavivirus, Japanese encephalitis virus (JEV), with high mortality. We designed several LNA gapmers targeting the 3\u2032 untranslated region of JEV genomic RNAs. In vitro screening by plaque assay using Vero cells revealed that LNA gapmers targeting a stem-loop region effectively inhibit JEV proliferation. Cell-based and RNA cleavage assays using mismatched LNA gapmers exhibited an underlying mechanism where the inhibition of viral production results from JEV RNA degradation by LNA gapmers in a sequence- and modification-dependent manner. Encouragingly, LNA gapmers potently inhibited the proliferation of five JEV strains of predominant genotypes I and III in human neuroblastoma cells without apparent cytotoxicity. Database searching showed a low possibility of off-target binding of our LNA gapmers to human RNAs. The target viral RNA sequence conservation observed here highlighted their broad-spectrum antiviral potential against different JEV genotypes\/strains. This work will facilitate the development of an antiviral LNA gapmer therapy for JEV and other flavivirus infections.<\/jats:p>","DOI":"10.3390\/ijms241914846","type":"journal-article","created":{"date-parts":[[2023,10,2]],"date-time":"2023-10-02T11:56:49Z","timestamp":1696247809000},"page":"14846","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Antiviral Efficacy of RNase H-Dependent Gapmer Antisense Oligonucleotides against Japanese Encephalitis Virus"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9465-0375","authenticated-orcid":false,"given":"Shunsuke","family":"Okamoto","sequence":"first","affiliation":[{"name":"Laboratory of Preventive Veterinary Medicine and Animal Health, Department of Veterinary Medicine, College of Bioresource Sciences, Nihon University, Fujisawa, Kanagawa 252-0880, Japan"},{"name":"Nihon University Veterinary Research Center, Fujisawa, Kanagawa 252-0880, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1573-4819","authenticated-orcid":false,"given":"Yusuke","family":"Echigoya","sequence":"additional","affiliation":[{"name":"Nihon University Veterinary Research Center, Fujisawa, Kanagawa 252-0880, Japan"},{"name":"Laboratory of Biomedical Science, Department of Veterinary Medicine, College of Bioresource Sciences, Nihon University, Fujisawa, Kanagawa 252-0880, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayaka","family":"Tago","sequence":"additional","affiliation":[{"name":"Nihon University Veterinary Research Center, Fujisawa, Kanagawa 252-0880, Japan"},{"name":"Laboratory of Biomedical Science, Department of Veterinary Medicine, College of Bioresource Sciences, Nihon University, Fujisawa, Kanagawa 252-0880, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takao","family":"Segawa","sequence":"additional","affiliation":[{"name":"Laboratory of Preventive Veterinary Medicine and Animal Health, Department of Veterinary Medicine, College of Bioresource Sciences, Nihon University, Fujisawa, Kanagawa 252-0880, Japan"},{"name":"Nihon University Veterinary Research Center, Fujisawa, Kanagawa 252-0880, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukita","family":"Sato","sequence":"additional","affiliation":[{"name":"Nihon University Veterinary Research Center, Fujisawa, Kanagawa 252-0880, Japan"},{"name":"Laboratory of Biomedical Science, Department of Veterinary Medicine, College of Bioresource Sciences, Nihon University, Fujisawa, Kanagawa 252-0880, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8570-6576","authenticated-orcid":false,"given":"Takuya","family":"Itou","sequence":"additional","affiliation":[{"name":"Laboratory of Preventive Veterinary Medicine and Animal Health, Department of Veterinary Medicine, College of Bioresource Sciences, Nihon University, Fujisawa, Kanagawa 252-0880, Japan"},{"name":"Nihon University Veterinary Research Center, Fujisawa, Kanagawa 252-0880, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Jo, S.J., Chae, S.U., Lee, C.B., and Bae, S.K. 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