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Since the approval of talimogene laherparepvec (T-VEC) in 2015, HSV has been thoroughly researched to discover novel mechanisms to combat cancer and treat other diseases. Another HSV-based drug, beremagene geperpavec (B-VEC), received approval in 2023 to treat the rare genetic disease dystrophic epidermolysis bullosa, and was also the first clinically approved HSV vector carrying an extracellular matrix (ECM)-modifying transgene. The ECM is a network of macromolecules surrounding cells, which provides support and regulates cell growth and differentiation, the disruption of which is common in cancer. The naked mole rat (NMR) has a thick ECM and a unique mutation in the hyaluronan synthase 2 (HAS2) gene, which has been linked to the high cancer resistance of the species. To study the effect of this mutation in human cancer, we have developed an attenuated, replication-competent HSV vector expressing the NMR-HAS2 gene. The viral replication, transgene expression and cytotoxic effect of the novel vector was studied in glioma cells. Our results show that an attenuated, replication-competent HSV vector expressing a foreign ECM-modifying transgene, namely HAS2, provides an effective tool to study and combat cancer in humans.<\/jats:p>","DOI":"10.3390\/microorganisms11112657","type":"journal-article","created":{"date-parts":[[2023,10,29]],"date-time":"2023-10-29T05:01:08Z","timestamp":1698555668000},"page":"2657","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Attenuated Replication-Competent Herpes Simplex Virus Expressing an ECM-Modifying Transgene Hyaluronan Synthase 2 of Naked Mole Rat in Oncolytic Gene Therapy"],"prefix":"10.3390","volume":"11","author":[{"given":"Jussi","family":"Palom\u00e4ki","sequence":"first","affiliation":[{"name":"Institute of Biomedicine, University of Turku, Kiinamyllynkatu 10, 20520 Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7832-2021","authenticated-orcid":false,"given":"Kiira","family":"Kalke","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine, University of Turku, Kiinamyllynkatu 10, 20520 Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julius","family":"Orpana","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine, University of Turku, Kiinamyllynkatu 10, 20520 Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0537-7651","authenticated-orcid":false,"given":"Liisa","family":"Lund","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine, University of Turku, Kiinamyllynkatu 10, 20520 Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0394-5849","authenticated-orcid":false,"given":"Fanny","family":"Frejborg","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine, University of Turku, Kiinamyllynkatu 10, 20520 Turku, Finland"},{"name":"Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering, \u00c5bo Akademi University, 20520 Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Paavilainen","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine, University of Turku, Kiinamyllynkatu 10, 20520 Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannu","family":"J\u00e4rvel\u00e4inen","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine, University of Turku, Kiinamyllynkatu 10, 20520 Turku, Finland"},{"name":"Department of Internal Medicine, Satakunta Hospital District, Satasairaala Central Hospital, Sairaalantie 3, 28500 Pori, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2867-7844","authenticated-orcid":false,"given":"Veijo","family":"Hukkanen","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine, University of Turku, Kiinamyllynkatu 10, 20520 Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"11307","DOI":"10.1073\/pnas.93.21.11307","article-title":"The Function of Herpes Simplex Virus Genes: A Primer for Genetic Engineering of Novel Vectors","volume":"93","author":"Roizman","year":"1996","journal-title":"Proc. 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