{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T08:07:18Z","timestamp":1770797238903,"version":"3.50.0"},"reference-count":63,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,4,14]],"date-time":"2025-04-14T00:00:00Z","timestamp":1744588800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["22-75-10087"],"award-info":[{"award-number":["22-75-10087"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["22-64-00057"],"award-info":[{"award-number":["22-64-00057"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The insertion of a transgene downstream of the L3-23K or L5-Fiber region was reported as a vital strategy for arming E3 non-deleted oncolytic adenoviruses. However, depending on the percentage of codons with G\/C at the third base position (GC3%) and the type of splicing acceptor, an insert downstream of the L5-Fiber region may substantially affect virus fitness. Since the insertion of transgenes downstream of the L3-23K and L5-Fiber regions has never been compared in terms of their expression levels and impact on virus fitness, we assessed the total virus yield, cytolytic efficacy, and plaque size of Ad5-delta-24-RGD (Ad5\u039424RGD) armed with EGFP, FLuc, the suppressor of RNA silencing p19, soluble wild-type human\/mouse and high-affinity human programmed cell death receptor-1 (PD-1\/PDCD1) ectodomains, and soluble human hyaluronidase PH20\/SPAM1. The insertion of transgenes downstream of the L3-23K region ensures their production at considerably higher levels. However, the insertion of transgenes downstream of either region differentially and unpredictably affects the oncolytic potency of Ad5\u039424RGD, which cannot be explained by GC3% or expression level alone. Surprisingly, the expression of the human and mouse PD-1 ectodomains with 83.1% and 70.1% GC3%, respectively, does not affect cytolytic efficacy but increases the plaque size in a cell line-dependent manner.<\/jats:p>","DOI":"10.3390\/ijms26083700","type":"journal-article","created":{"date-parts":[[2025,4,14]],"date-time":"2025-04-14T09:06:51Z","timestamp":1744621611000},"page":"3700","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Comparison of the L3-23K and L5-Fiber Regions for Arming the Oncolytic Adenovirus Ad5-Delta-24-RGD with Reporter and Therapeutic Transgenes"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3821-6846","authenticated-orcid":false,"given":"Aleksei A.","family":"Stepanenko","sequence":"first","affiliation":[{"name":"Department of Fundamental and Applied Neurobiology, V. P. Serbsky National Medical Research Center of Psychiatry and Narcology, Ministry of Health of the Russian Federation, 119034 Moscow, Russia"},{"name":"Department of Medical Nanobiotechnology, Institute of Translational Medicine, N. I. Pirogov Russian National Research Medical University, Ministry of Health of the Russian Federation, 117997 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anastasiia O.","family":"Sosnovtseva","sequence":"additional","affiliation":[{"name":"Department of Fundamental and Applied Neurobiology, V. P. Serbsky National Medical Research Center of Psychiatry and Narcology, Ministry of Health of the Russian Federation, 119034 Moscow, Russia"},{"name":"Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia"},{"name":"Laboratory of Regulation of Intracellular Proteolysis, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8988-3417","authenticated-orcid":false,"given":"Marat P.","family":"Valikhov","sequence":"additional","affiliation":[{"name":"Department of Fundamental and Applied Neurobiology, V. P. Serbsky National Medical Research Center of Psychiatry and Narcology, Ministry of Health of the Russian Federation, 119034 Moscow, Russia"},{"name":"Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-8549-5457","authenticated-orcid":false,"given":"Anastasiia A.","family":"Vasiukova","sequence":"additional","affiliation":[{"name":"Department of Fundamental and Applied Neurobiology, V. P. Serbsky National Medical Research Center of Psychiatry and Narcology, Ministry of Health of the Russian Federation, 119034 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8793-1833","authenticated-orcid":false,"given":"Olga V.","family":"Abramova","sequence":"additional","affiliation":[{"name":"Department of Fundamental and Applied Neurobiology, V. P. Serbsky National Medical Research Center of Psychiatry and Narcology, Ministry of Health of the Russian Federation, 119034 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anastasiia V.","family":"Lipatova","sequence":"additional","affiliation":[{"name":"Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3056-4889","authenticated-orcid":false,"given":"Gaukhar M.","family":"Yusubalieva","sequence":"additional","affiliation":[{"name":"Laboratory of Cell Technologies, Federal Scientific and Clinical Center for Specialized Types of Medical Care and Medical Technologies, Federal Medical and Biological Agency of the Russian Federation, 115682 Moscow, Russia"},{"name":"Laboratory of Immunotherapy of Solid Tumors, Federal Center for Brain and Neurotechnology, Federal Medical and Biological Agency of the Russian Federation, 117513 Moscow, Russia"},{"name":"Laboratory of Molecular Mechanisms of Regeneration, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vladimir P.","family":"Chekhonin","sequence":"additional","affiliation":[{"name":"Department of Fundamental and Applied Neurobiology, V. P. Serbsky National Medical Research Center of Psychiatry and Narcology, Ministry of Health of the Russian Federation, 119034 Moscow, Russia"},{"name":"Department of Medical Nanobiotechnology, Institute of Translational Medicine, N. I. Pirogov Russian National Research Medical University, Ministry of Health of the Russian Federation, 117997 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.virol.2020.05.016","article-title":"OvirusTdb: A database of oncolytic viruses for the advancement of therapeutics in cancer","volume":"548","author":"Lathwal","year":"2020","journal-title":"Virology"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Blanchette, P., and Teodoro, J.G. (2023). A Renaissance for Oncolytic Adenoviruses?. 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