{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T20:35:20Z","timestamp":1782333320595,"version":"3.54.5"},"reference-count":41,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2024,8,20]],"date-time":"2024-08-20T00:00:00Z","timestamp":1724112000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,8,20]],"date-time":"2024-08-20T00:00:00Z","timestamp":1724112000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000050","name":"HHS | NIH | National Heart, Lung, and Blood Institute","doi-asserted-by":"crossref","award":["R01HL089221"],"award-info":[{"award-number":["R01HL089221"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000065","name":"HHS | NIH | National Institute of Neurological Disorders and Stroke","doi-asserted-by":"crossref","award":["R01NS099371"],"award-info":[{"award-number":["R01NS099371"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000057","name":"HHS | NIH | National Institute of General Medical Sciences","doi-asserted-by":"crossref","award":["R01GM127708"],"award-info":[{"award-number":["R01GM127708"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2024,8,20]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              Many viruses have evolved structured RNA elements that can influence transcript abundance and translational efficiency, and help evade host immune factors by hijacking cellular machinery during replication. Here, we evaluated the functional impact of sub-genomic flaviviral RNAs (sfRNAs) known to stall exoribonuclease activity, by incorporating these elements into recombinant adeno-associated viral (AAV) genome cassettes. Specifically, sfRNAs from Dengue, Zika, Japanese Encephalitis, Yellow Fever, Murray Valley Encephalitis, and West Nile viruses increased transcript stability and transgene expression compared to a conventional woodchuck hepatitis virus element (WPRE). Further dissection of engineered transcripts revealed that sfRNA elements (i) require incorporation in\n              <jats:italic>cis<\/jats:italic>\n              within the 3\u2032 untranslated region (UTR) of AAV genomes, (ii) require minimal dumbbell structures to exert the observed effects, and (iii) can stabilize AAV transcripts independent of 5\u2032\u22123\u2032 exoribonuclease 1 (XRN1)-mediated decay. Additionally, preliminary\n              <jats:italic>in vivo<\/jats:italic>\n              assessment of AAV vectors bearing sfRNA elements in mice achieved increased transcript abundance and expression in cardiac tissue. Leveraging the functional versatility of engineered viral RNA elements may help improve the potency of AAV vector-based gene therapies.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>Viral RNA elements can hijack host cell machinery to control stability of transcripts and consequently, infection. Studies that help better understand such viral elements can provide insights into antiviral strategies and also potentially leverage these features for therapeutic applications. In this study, by incorporating structured flaviviral RNA elements into recombinant adeno-associated viral (AAV) vector genomes, we show improved AAV transcript stability and transgene expression can be achieved, with implications for gene transfer.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/jvi.00095-24","type":"journal-article","created":{"date-parts":[[2024,7,31]],"date-time":"2024-07-31T13:51:32Z","timestamp":1722433892000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":2,"title":["Sub-genomic flaviviral RNA elements increase the stability and abundance of recombinant AAV vector transcripts"],"prefix":"10.1128","volume":"98","author":[{"given":"Rita M.","family":"Meganck","sequence":"first","affiliation":[{"name":"Department of Surgery, Duke University School of Medicine, Durham, North Carolina, USA"},{"name":"Gene Therapy Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA"},{"name":"Department of Molecular Microbiology, Washington University in St. Louis School of Medicine, St. Louis, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roza","family":"Ogurlu","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Duke University, Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiacheng","family":"Liu","sequence":"additional","affiliation":[{"name":"Gene Therapy Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA"},{"name":"Cornell University, Ithaca, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven","family":"Moller-Tank","sequence":"additional","affiliation":[{"name":"Gene Therapy Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA"},{"name":"Regeneron Pharmaceutical, Inc., Tarrytown, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Tse","sequence":"additional","affiliation":[{"name":"Gene Therapy Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA"},{"name":"Saint Louis University School of Medicine, St. Louis, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leo O.","family":"Blondel","sequence":"additional","affiliation":[{"name":"Department of Surgery, Duke University School of Medicine, Durham, North Carolina, USA"},{"name":"Department of Cell Biology &amp; Physiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Rosales","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Duke University, Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron C.","family":"Hall","sequence":"additional","affiliation":[{"name":"Department of Surgery, Duke University School of Medicine, Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather A.","family":"Vincent","sequence":"additional","affiliation":[{"name":"Department of Surgery, Duke University School of Medicine, Durham, North Carolina, USA"},{"name":"TorqueBio, Inc., Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathaniel J.","family":"Moorman","sequence":"additional","affiliation":[{"name":"Department of Microbiology &amp; Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William F.","family":"Marzluff","sequence":"additional","affiliation":[{"name":"Department of Biochemistry &amp; Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5563-4877","authenticated-orcid":true,"given":"Aravind","family":"Asokan","sequence":"additional","affiliation":[{"name":"Department of Surgery, Duke University School of Medicine, Durham, North Carolina, USA"},{"name":"Department of Biomedical Engineering, Duke University, Durham, North Carolina, USA"},{"name":"Department of Molecular Genetics &amp; Microbiology, Duke University School of Medicine, Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2022.09.015"},{"key":"e_1_3_3_3_2","first-page":"15","volume-title":"Parvoviruses","author":"Bowles DE","year":"2006","unstructured":"Bowles DE, Rabinowitz JE, Samulski RJ. 2006. 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