{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T07:55:15Z","timestamp":1790668515002,"version":"4.1.0"},"reference-count":71,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["AAPS J"],"DOI":"10.1208\/s12248-026-01267-2","type":"journal-article","created":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T21:28:01Z","timestamp":1787174881000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Industry Perspective on Translational and Clinical Pharmacology Aspects of Viral-based Gene Therapies and Vaccines\u2014Key Considerations and Learnings From Approved Products"],"prefix":"10.1208","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-6359-9462","authenticated-orcid":false,"given":"Hardik","family":"Mody","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jatin","family":"Narula","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prathap Nagaraja","family":"Shastri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dale","family":"Miles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vittal","family":"Shivva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jimit","family":"Raghav","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gillie","family":"Roth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anshul","family":"Gupta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bahru","family":"Habtemariam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvatore","family":"Iovino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Louie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nagendra Venkata","family":"Chemuturi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,19]]},"reference":[{"key":"1267_CR1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aan4672","author":"CE Dunbar","year":"2018","unstructured":"Dunbar CE, High KA, Joung JK, et al. Gene therapy comes of age. Science. 2018. https:\/\/doi.org\/10.1126\/science.aan4672.","journal-title":"Science"},{"key":"1267_CR2","doi-asserted-by":"publisher","first-page":"5820","DOI":"10.1038\/s41467-020-19505-2","volume":"11","author":"K Bulaklak","year":"2020","unstructured":"Bulaklak K, Gersbach CA. The once and future gene therapy. Nat Commun. 2020;11:5820. https:\/\/doi.org\/10.1038\/s41467-020-19505-2.","journal-title":"Nat Commun"},{"key":"1267_CR3","doi-asserted-by":"publisher","first-page":"630","DOI":"10.1038\/s41565-021-00898-0","volume":"16","author":"JA Kulkarni","year":"2021","unstructured":"Kulkarni JA, Witzigmann D, Thomson SB, et al. The current landscape of nucleic acid therapeutics. Nat Nanotechnol. 2021;16:630\u201343. https:\/\/doi.org\/10.1038\/s41565-021-00898-0.","journal-title":"Nat Nanotechnol"},{"key":"1267_CR4","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1038\/s41392-021-00487-6","volume":"6","author":"JT Bulcha","year":"2021","unstructured":"Bulcha JT, Wang Y, Ma H, et al. Viral vector platforms within the gene therapy landscape. Signal Transduct Target Ther. 2021;6:53. https:\/\/doi.org\/10.1038\/s41392-021-00487-6.","journal-title":"Signal Transduct Target Ther"},{"key":"1267_CR5","doi-asserted-by":"publisher","DOI":"10.1002\/btm2.10258","volume":"7","author":"Z Zhao","year":"2022","unstructured":"Zhao Z, Anselmo AC, Mitragotri S. Viral vector-based gene therapies in the clinic. Bioeng Transl Med. 2022;7:e10258. https:\/\/doi.org\/10.1002\/btm2.10258.","journal-title":"Bioeng Transl Med"},{"key":"1267_CR6","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1038\/s12276-022-00757-5","volume":"54","author":"Y-K Kim","year":"2022","unstructured":"Kim Y-K. RNA therapy: rich history, various applications and unlimited future prospects. Exp Mol Med. 2022;54:455\u201365. https:\/\/doi.org\/10.1038\/s12276-022-00757-5.","journal-title":"Exp Mol Med"},{"key":"1267_CR7","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1056\/nejmoa2107454","volume":"385","author":"JD Gillmore","year":"2021","unstructured":"Gillmore JD, Gane E, Taubel J, et al. CRISPR-Cas9 In Vivo Gene Editing for Transthyretin Amyloidosis. N Engl J Med. 2021;385:493\u2013502. https:\/\/doi.org\/10.1056\/nejmoa2107454.","journal-title":"N Engl J Med"},{"key":"1267_CR8","doi-asserted-by":"publisher","first-page":"3376","DOI":"10.1016\/j.ymthe.2023.11.001","volume":"31","author":"D Chancellor","year":"2023","unstructured":"Chancellor D, Barrett D, Nguyen-Jatkoe L, et al. The state of cell and gene therapy in 2023. Mol Ther. 2023;31:3376\u201388. https:\/\/doi.org\/10.1016\/j.ymthe.2023.11.001.","journal-title":"Mol Ther"},{"key":"1267_CR9","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1038\/s41573-019-0012-9","volume":"18","author":"D Wang","year":"2019","unstructured":"Wang D, Tai PWL, Gao G. Adeno-associated virus vector as a platform for gene therapy delivery. Nat Rev Drug Discov. 2019;18:358\u201378. https:\/\/doi.org\/10.1038\/s41573-019-0012-9.","journal-title":"Nat Rev Drug Discov"},{"key":"1267_CR10","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1038\/s41576-019-0205-4","volume":"21","author":"C Li","year":"2020","unstructured":"Li C, Samulski RJ. Engineering adeno-associated virus vectors for gene therapy. Nat Rev Genet. 2020;21:255\u201372. https:\/\/doi.org\/10.1038\/s41576-019-0205-4.","journal-title":"Nat Rev Genet"},{"key":"1267_CR11","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-024-01780-w","volume":"9","author":"J-H Wang","year":"2024","unstructured":"Wang J-H, Gessler DJ, Zhan W, et al. Adeno-associated virus as a delivery vector for gene therapy of human diseases. Signal Transduct Target Ther. 2024;9:78. https:\/\/doi.org\/10.1038\/s41392-024-01780-w.","journal-title":"Signal Transduct Target Ther"},{"key":"1267_CR12","doi-asserted-by":"publisher","unstructured":"Bouchard P, Chand DH, Tukov FF, et al. Development of Gene Therapies, Strategic, Scientific, Regulatory, and Access Considerations 2024:31\u201366. https:\/\/doi.org\/10.1201\/9781003230342-3.","DOI":"10.1201\/9781003230342-3"},{"key":"1267_CR13","unstructured":"BEQVEZ n.d. https:\/\/www.fda.gov\/vaccines-blood-biologics\/cellular-gene-therapy-products\/beqvez (accessed October 21, 2025)."},{"key":"1267_CR14","unstructured":"ZOLGENSMA n.d. https:\/\/www.fda.gov\/vaccines-blood-biologics\/zolgensma (accessed October 21, 2025)."},{"key":"1267_CR15","unstructured":"ELEVIDYS n.d. https:\/\/www.fda.gov\/vaccines-blood-biologics\/tissue-tissue-products\/elevidys (accessed October 21, 2025)."},{"key":"1267_CR16","unstructured":"HEMGENIX n.d. https:\/\/www.fda.gov\/vaccines-blood-biologics\/vaccines\/hemgenix (accessed October 21, 2025)."},{"key":"1267_CR17","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1016\/j.ymthe.2017.12.009","volume":"26","author":"S Bunting","year":"2018","unstructured":"Bunting S, Zhang L, Xie L, et al. Gene therapy with BMN 270 results in therapeutic levels of FVIII in mice and primates and normalization of bleeding in hemophilic mice. Mol Ther. 2018;26:496\u2013509. https:\/\/doi.org\/10.1016\/j.ymthe.2017.12.009.","journal-title":"Mol Ther"},{"key":"1267_CR18","unstructured":"ROCTAVIAN n.d. https:\/\/www.fda.gov\/vaccines-blood-biologics\/roctavian (accessed October 21, 2025)."},{"key":"1267_CR19","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1016\/j.ymthe.2006.04.008","volume":"14","author":"JR Forsayeth","year":"2006","unstructured":"Forsayeth JR, Eberling JL, Sanftner LM, et al. A dose-ranging study of AAV-hAADC therapy in parkinsonian monkeys. Mol Ther. 2006;14:571\u20137. https:\/\/doi.org\/10.1016\/j.ymthe.2006.04.008.","journal-title":"Mol Ther"},{"key":"1267_CR20","doi-asserted-by":"publisher","first-page":"1458","DOI":"10.1038\/mt.2010.106","volume":"18","author":"P Hadaczek","year":"2010","unstructured":"Hadaczek P, Eberling JL, Pivirotto P, et al. Eight years of clinical improvement in MPTP-lesioned primates after gene therapy with AAV2-hAADC. Mol Ther. 2010;18:1458\u201361. https:\/\/doi.org\/10.1038\/mt.2010.106.","journal-title":"Mol Ther"},{"key":"1267_CR21","doi-asserted-by":"publisher","first-page":"564","DOI":"10.1016\/j.ymthe.2006.05.005","volume":"14","author":"KS Bankiewicz","year":"2006","unstructured":"Bankiewicz KS, Forsayeth J, Eberling JL, et al. Long-term clinical improvement in MPTP-lesioned primates after gene therapy with AAV-hAADC. Mol Ther. 2006;14:564\u201370. https:\/\/doi.org\/10.1016\/j.ymthe.2006.05.005.","journal-title":"Mol Ther"},{"key":"1267_CR22","unstructured":"UPSTAZA: EMA Assessment report n.d. https:\/\/www.ema.europa.eu\/en\/documents\/assessment-report\/upstaza-epar-public-assessment-report_en.pdf (accessed October 21, 2025)."},{"key":"1267_CR23","doi-asserted-by":"publisher","first-page":"S79","DOI":"10.1002\/jcph.2141","volume":"62","author":"K Sun","year":"2022","unstructured":"Sun K, Liao MZ. Clinical pharmacology considerations on recombinant adeno\u2010associated virus\u2013based gene therapy. J Clin Pharmacol. 2022;62:S79-94. https:\/\/doi.org\/10.1002\/jcph.2141.","journal-title":"J Clin Pharmacol"},{"key":"1267_CR24","unstructured":"US Food and Drug Administration. Guidance for industry: Considerations for the Design of Early-Phase Clinical Trials of Cellular and Gene Therapy Products. June 2015. n.d.\u00a0https:\/\/www.fda.gov\/regulatory-information\/search-fda-guidance-documents\/considerations-design-early-phase-clinical-trials-cellular-and-gene-therapy-products."},{"key":"1267_CR25","doi-asserted-by":"publisher","first-page":"1207","DOI":"10.1002\/cpt.2224","volume":"110","author":"A McIntosh","year":"2021","unstructured":"McIntosh A, Sverdlov O, Yu L, et al. Clinical design and analysis strategies for the development of gene therapies: considerations for quantitative drug development in the age of genetic medicine. Clin Pharmacol Ther. 2021;110:1207\u201315. https:\/\/doi.org\/10.1002\/cpt.2224.","journal-title":"Clin Pharmacol Ther"},{"key":"1267_CR26","doi-asserted-by":"publisher","unstructured":"Kaufmann P, Haidet-Phillips A. Development of Gene Therapies, Strategic, Scientific, Regulatory, and Access Considerations 2024:101\u201326. https:\/\/doi.org\/10.1201\/9781003230342-5.","DOI":"10.1201\/9781003230342-5"},{"key":"1267_CR27","doi-asserted-by":"publisher","unstructured":"Sverdlov O, McIntosh A, Aksenov S, et al. Development of Gene Therapies, Strategic, Scientific, Regulatory, and Access Considerations 2024:217\u201350. https:\/\/doi.org\/10.1201\/9781003230342-10.","DOI":"10.1201\/9781003230342-10"},{"key":"1267_CR28","doi-asserted-by":"publisher","first-page":"803","DOI":"10.1002\/cpt.2269","volume":"110","author":"F Tang","year":"2021","unstructured":"Tang F, Wong H, Ng CM. Rational clinical dose selection of adeno\u2010associated virus\u2010mediated gene therapy based on allometric principles. Clin Pharmacol Ther. 2021;110:803\u20137. https:\/\/doi.org\/10.1002\/cpt.2269.","journal-title":"Clin Pharmacol Ther"},{"key":"1267_CR29","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1016\/j.addr.2021.01.017","volume":"170","author":"EA Chowdhury","year":"2021","unstructured":"Chowdhury EA, Meno-Tetang G, Chang HY, et al. Current progress and limitations of AAV mediated delivery of protein therapeutic genes and the importance of developing quantitative pharmacokinetic\/pharmacodynamic (PK\/PD) models. Adv Drug Deliv Rev. 2021;170:214\u201337. https:\/\/doi.org\/10.1016\/j.addr.2021.01.017.","journal-title":"Adv Drug Deliv Rev"},{"key":"1267_CR30","doi-asserted-by":"publisher","unstructured":"Rao S, Narula J, Ko G, et al. Development of Gene Therapies, Strategic, Scientific, Regulatory, and Access Considerations 2024:67\u2013100. https:\/\/doi.org\/10.1201\/9781003230342-4.","DOI":"10.1201\/9781003230342-4"},{"key":"1267_CR31","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1016\/j.xphs.2023.10.005","volume":"113","author":"S Liu","year":"2024","unstructured":"Liu S, Chowdhury EA, Xu V, et al. Whole-body disposition and physiologically based pharmacokinetic modeling of adeno-associated viruses and the transgene product. J Pharm Sci. 2024;113:141\u201357. https:\/\/doi.org\/10.1016\/j.xphs.2023.10.005.","journal-title":"J Pharm Sci"},{"key":"1267_CR32","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-025-01155-1","volume":"27","author":"MA Tegenge","year":"2025","unstructured":"Tegenge MA, Yogurtcu ON, Belov AA, et al. Physiologically based pharmacokinetic modeling and simulation in regulatory review: US FDA CBER experience and perspectives. AAPS J. 2025;27:157. https:\/\/doi.org\/10.1208\/s12248-025-01155-1.","journal-title":"AAPS J"},{"key":"1267_CR33","doi-asserted-by":"publisher","first-page":"1531","DOI":"10.1007\/s40262-025-01535-y","volume":"64","author":"J Wojciechowski","year":"2025","unstructured":"Wojciechowski J, Gaitonde P, Hughes JH, et al. Population modeling of factor IX activity following administration of fidanacogene elaparvovec gene therapy in participants with hemophilia B. Clin Pharmacokinet. 2025;64:1531\u201348. https:\/\/doi.org\/10.1007\/s40262-025-01535-y.","journal-title":"Clin Pharmacokinet"},{"key":"1267_CR34","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.1082797","volume":"13","author":"RK Omole","year":"2022","unstructured":"Omole RK, Oluwatola O, Akere MT, et al. Comprehensive assessment on the applications of oncolytic viruses for cancer immunotherapy. Front Pharmacol. 2022;13:1082797. https:\/\/doi.org\/10.3389\/fphar.2022.1082797.","journal-title":"Front Pharmacol"},{"key":"1267_CR35","first-page":"4192","volume":"14","author":"K Li","year":"2022","unstructured":"Li K, Zhao Y, Hu X, et al. Advances in the clinical development of oncolytic viruses. Am J Transl Res. 2022;14:4192\u2013206.","journal-title":"Am J Transl Res"},{"key":"1267_CR36","doi-asserted-by":"publisher","first-page":"1107","DOI":"10.1016\/j.ymthe.2017.03.026","volume":"25","author":"SJ Russell","year":"2017","unstructured":"Russell SJ, Peng K-W. Oncolytic virotherapy: a contest between apples and oranges. Mol Ther. 2017;25:1107\u201316. https:\/\/doi.org\/10.1016\/j.ymthe.2017.03.026.","journal-title":"Mol Ther"},{"key":"1267_CR37","doi-asserted-by":"publisher","first-page":"1212","DOI":"10.1002\/cpt.3230","volume":"115","author":"JL Ford","year":"2024","unstructured":"Ford JL, Karatza E, Mody H, et al. Clinical pharmacology perspective on development of adeno\u2010associated virus vector\u2010based retina gene therapy. Clin Pharmacol Ther. 2024;115:1212\u201332. https:\/\/doi.org\/10.1002\/cpt.3230.","journal-title":"Clin Pharmacol Ther"},{"key":"1267_CR38","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13061383","volume":"13","author":"PF Ferrucci","year":"2021","unstructured":"Ferrucci PF, Pala L, Conforti F, et al. Talimogene laherparepvec (T-VEC): an intralesional cancer immunotherapy for advanced melanoma. Cancers. 2021;13:1383. https:\/\/doi.org\/10.3390\/cancers13061383.","journal-title":"Cancers"},{"key":"1267_CR39","unstructured":"IMLYGIC n.d. https:\/\/www.fda.gov\/vaccines-blood-biologics\/cellular-gene-therapy-products\/imlygic (accessed October 21, 2025)."},{"key":"1267_CR40","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-31262-y","volume":"13","author":"T Todo","year":"2022","unstructured":"Todo T, Ino Y, Ohtsu H, et al. A phase I\/II study of triple-mutated oncolytic herpes virus G47\u2206 in patients with progressive glioblastoma. Nat Commun. 2022;13:4119. https:\/\/doi.org\/10.1038\/s41467-022-31262-y.","journal-title":"Nat Commun"},{"key":"1267_CR41","doi-asserted-by":"publisher","first-page":"528","DOI":"10.1200\/jco.22.00343","volume":"41","author":"JA Chesney","year":"2023","unstructured":"Chesney JA, Ribas A, Long GV, et al. Randomized, double-blind, placebo-controlled, global phase III trial of talimogene laherparepvec combined with pembrolizumab for advanced melanoma. J Clin Oncol. 2023;41:528\u201340. https:\/\/doi.org\/10.1200\/jco.22.00343.","journal-title":"J Clin Oncol"},{"key":"1267_CR42","doi-asserted-by":"publisher","first-page":"4169","DOI":"10.1245\/s10434-016-5286-0","volume":"23","author":"RHI Andtbacka","year":"2016","unstructured":"Andtbacka RHI, Ross M, Puzanov I, et al. Patterns of clinical response with talimogene laherparepvec (T-VEC) in patients with melanoma treated in the OPTiM phase III clinical trial. Ann Surg Oncol. 2016;23:4169\u201377. https:\/\/doi.org\/10.1245\/s10434-016-5286-0.","journal-title":"Ann Surg Oncol"},{"key":"1267_CR43","unstructured":"Project Optimus | FDA n.d. https:\/\/www.fda.gov\/about-fda\/oncology-center-excellence\/project-optimus (accessed May 31, 2026)."},{"key":"1267_CR44","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.705443","volume":"12","author":"ZP Parra-Guillen","year":"2021","unstructured":"Parra-Guillen ZP, Freshwater T, Cao Y, et al. Mechanistic modeling of a novel oncolytic virus, V937, to describe viral kinetic and dynamic processes following intratumoral and intravenous administration. Front Pharmacol. 2021;12:705443. https:\/\/doi.org\/10.3389\/fphar.2021.705443.","journal-title":"Front Pharmacol"},{"key":"1267_CR45","doi-asserted-by":"publisher","first-page":"753","DOI":"10.1016\/j.hoc.2017.06.007","volume":"31","author":"T Athanasopoulos","year":"2017","unstructured":"Athanasopoulos T, Munye MM, Y\u00e1\u00f1ez-Mu\u00f1oz RJ. Nonintegrating gene therapy vectors. Hematol Oncol Clin North Am. 2017;31:753\u201370. https:\/\/doi.org\/10.1016\/j.hoc.2017.06.007.","journal-title":"Hematol Oncol Clin North Am"},{"key":"1267_CR46","unstructured":"ADSTILADRIN n.d. https:\/\/www.fda.gov\/vaccines-blood-biologics\/cellular-gene-therapy-products\/adstiladrin (accessed October 21, 2025)."},{"key":"1267_CR47","unstructured":"VYJUVEK n.d. https:\/\/www.fda.gov\/vaccines-blood-biologics\/vyjuvek (accessed October 21, 2025)."},{"key":"1267_CR48","doi-asserted-by":"publisher","DOI":"10.3390\/v15030698","volume":"15","author":"K Lundstrom","year":"2023","unstructured":"Lundstrom K. Viral vectors in gene therapy: where do we stand in 2023? Viruses. 2023;15:698. https:\/\/doi.org\/10.3390\/v15030698.","journal-title":"Viruses"},{"key":"1267_CR49","doi-asserted-by":"publisher","first-page":"13561","DOI":"10.1093\/nar\/gkae1069","volume":"52","author":"KL Kanke","year":"2024","unstructured":"Kanke KL, Rayner RE, Bozik J, et al. Single-stranded DNA with internal base modifications mediates highly efficient knock-in in primary cells using CRISPR-Cas9. Nucleic Acids Res. 2024;52:13561\u201376. https:\/\/doi.org\/10.1093\/nar\/gkae1069.","journal-title":"Nucleic Acids Res"},{"key":"1267_CR50","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2221127120","volume":"120","author":"W Han","year":"2023","unstructured":"Han W, Li Z, Guo Y, et al. Efficient precise integration of large DNA sequences with 3\u2032-overhang dsDNA donors using CRISPR\/Cas9. Proc Natl Acad Sci U S A. 2023;120:e2221127120. https:\/\/doi.org\/10.1073\/pnas.2221127120.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"1267_CR51","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1016\/j.ymthe.2020.01.001","volume":"28","author":"JL Shirley","year":"2020","unstructured":"Shirley JL, Jong Y, Terhorst C, et al. Immune responses to viral gene therapy vectors. Mol Ther. 2020;28:709\u201322. https:\/\/doi.org\/10.1016\/j.ymthe.2020.01.001.","journal-title":"Mol Ther"},{"key":"1267_CR52","doi-asserted-by":"publisher","first-page":"737","DOI":"10.3390\/v1030737","volume":"1","author":"J Melchjorsen","year":"2009","unstructured":"Melchjorsen J, Matikainen S, Paludan SR. Activation and evasion of innate antiviral immunity by herpes simplex virus. Viruses. 2009;1:737\u201359. https:\/\/doi.org\/10.3390\/v1030737.","journal-title":"Viruses"},{"key":"1267_CR53","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1186\/s12985-016-0495-5","volume":"13","author":"C Su","year":"2016","unstructured":"Su C, Zhan G, Zheng C. Evasion of host antiviral innate immunity by HSV-1, an update. Virol J. 2016;13:38. https:\/\/doi.org\/10.1186\/s12985-016-0495-5.","journal-title":"Virol J"},{"key":"1267_CR54","doi-asserted-by":"publisher","first-page":"2211","DOI":"10.1056\/nejmoa2206663","volume":"387","author":"SV Guide","year":"2022","unstructured":"Guide SV, Gonzalez ME, Ba\u011fc\u0131 IS, et al. Trial of Beremagene Geperpavec (B-VEC) for dystrophic epidermolysis bullosa. N Engl J Med. 2022;387:2211\u20139. https:\/\/doi.org\/10.1056\/nejmoa2206663.","journal-title":"N Engl J Med"},{"key":"1267_CR55","doi-asserted-by":"publisher","first-page":"780","DOI":"10.1038\/s41591-022-01737-y","volume":"28","author":"I Gurevich","year":"2022","unstructured":"Gurevich I, Agarwal P, Zhang P, et al. In vivo topical gene therapy for recessive dystrophic epidermolysis bullosa: a phase 1 and 2 trial. Nat Med. 2022;28:780\u20138. https:\/\/doi.org\/10.1038\/s41591-022-01737-y.","journal-title":"Nat Med"},{"key":"1267_CR56","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1016\/j.urology.2005.02.015","volume":"66","author":"RJ Connor","year":"2005","unstructured":"Connor RJ, Anderson JM, Machemer T, et al. Sustained intravesical interferon protein exposure is achieved using an adenoviral-mediated gene delivery system: a study in rats evaluating dosing regimens. Urology. 2005;66:224\u20139. https:\/\/doi.org\/10.1016\/j.urology.2005.02.015.","journal-title":"Urology"},{"key":"1267_CR57","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1038\/sj.cgt.7700865","volume":"13","author":"Z Tao","year":"2006","unstructured":"Tao Z, Connor RJ, Ashoori F, et al. Efficacy of a single intravesical treatment with Ad-IFN\/Syn 3 is dependent on dose and urine IFN concentration obtained: implications for clinical investigation. Cancer Gene Ther. 2006;13:125\u201330. https:\/\/doi.org\/10.1038\/sj.cgt.7700865.","journal-title":"Cancer Gene Ther"},{"key":"1267_CR58","doi-asserted-by":"publisher","first-page":"850","DOI":"10.1016\/j.juro.2013.03.030","volume":"190","author":"CPN Dinney","year":"2013","unstructured":"Dinney CPN, Fisher MB, Navai N, et al. Phase I trial of intravesical recombinant adenovirus mediated interferon-\u03b12b formulated in Syn3 for bacillus calmette-gu\u00e9rin failures in nonmuscle invasive bladder cancer. J Urol. 2013;190:850\u20136. https:\/\/doi.org\/10.1016\/j.juro.2013.03.030.","journal-title":"J Urol"},{"key":"1267_CR59","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/s1470-2045(20)30540-4","volume":"22","author":"SA Boorjian","year":"2021","unstructured":"Boorjian SA, Alemozaffar M, Konety BR, et al. Intravesical nadofaragene firadenovec gene therapy for BCG-unresponsive non-muscle-invasive bladder cancer: a single-arm, open-label, repeat-dose clinical trial. Lancet Oncol. 2021;22:107\u201317. https:\/\/doi.org\/10.1016\/s1470-2045(20)30540-4.","journal-title":"Lancet Oncol"},{"key":"1267_CR60","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2017.72.3064","author":"ND Shore","year":"2017","unstructured":"Shore ND, Boorjian SA, Canter DJ, et al. Intravesical rAd\u2013IFN\u03b1\/Syn3 for patients with high-grade, bacillus calmette-guerin\u2013refractory or relapsed non\u2013muscle-invasive bladder cancer: a phase II randomized study. J Clin Oncol. 2017. https:\/\/doi.org\/10.1200\/jco.2017.72.3064.","journal-title":"J Clin Oncol"},{"issue":"Suppl 6","key":"1267_CR61","first-page":"S22","volume":"7","author":"V Chalana","year":"2005","unstructured":"Chalana V, Dudycha S, Yuk J-T, et al. Automatic Measurement of Ultrasound-Estimated Bladder Weight (UEBW) from Three-Dimensional Ultrasound. Rev Urol. 2005;7(Suppl 6):S22\u20138.","journal-title":"Rev Urol"},{"issue":"8","key":"1267_CR62","doi-asserted-by":"publisher","first-page":"R752","DOI":"10.1152\/ajpregu.00450.2015","volume":"310","author":"K Kadekawa","year":"2016","unstructured":"Kadekawa K, Yoshimura N, Majima T, et al. Characterization of bladder and external urethral activity in mice with or without spinal cord injury\u2014a comparison study with rats. Am J Physiol Regul Integr Comp Physiol. 2016;310(8):R752. https:\/\/doi.org\/10.1152\/ajpregu.00450.2015.","journal-title":"Am J Physiol Regul Integr Comp Physiol"},{"key":"1267_CR63","doi-asserted-by":"publisher","DOI":"10.1038\/s41541-022-00503-y","volume":"7","author":"T Travieso","year":"2022","unstructured":"Travieso T, Li J, Mahesh S, et al. The use of viral vectors in vaccine development. NPJ Vaccines. 2022;7:75. https:\/\/doi.org\/10.1038\/s41541-022-00503-y.","journal-title":"NPJ Vaccines"},{"key":"1267_CR64","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2022.102210","volume":"77","author":"N McCann","year":"2022","unstructured":"McCann N, O\u2019Connor D, Lambe T, et al. Viral vector vaccines. Curr Opin Immunol. 2022;77:102210. https:\/\/doi.org\/10.1016\/j.coi.2022.102210.","journal-title":"Curr Opin Immunol"},{"issue":"1","key":"1267_CR65","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1038\/s41392-023-01408-5","volume":"8","author":"S Wang","year":"2023","unstructured":"Wang S, Liang B, Wang W, et al. Viral vectored vaccines: design, development, preventive and therapeutic applications in human diseases. Signal Transduct Target Ther. 2023;8:149. https:\/\/doi.org\/10.1038\/s41392-023-01408-5.","journal-title":"Signal Transduct Target Ther"},{"key":"1267_CR66","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines9030190","volume":"9","author":"J Wolf","year":"2021","unstructured":"Wolf J, Jannat R, Dubey S, et al. Development of pandemic vaccines: ERVEBO case study. Vaccines. 2021;9:190. https:\/\/doi.org\/10.3390\/vaccines9030190.","journal-title":"Vaccines"},{"key":"1267_CR67","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvacx.2019.100009","volume":"1","author":"TP Monath","year":"2019","unstructured":"Monath TP, Fast PE, Modjarrad K, et al. rVSV\u0394G-ZEBOV-GP (also designated V920) recombinant vesicular stomatitis virus pseudotyped with Ebola Zaire glycoprotein: standardized template with key considerations for a risk\/benefit assessment. Vaccine: X. 2019;1:100009. https:\/\/doi.org\/10.1016\/j.jvacx.2019.100009.","journal-title":"Vaccine: X"},{"key":"1267_CR68","unstructured":"Background document on the Janssen Ad26.COV2.S (COVID-19) vaccine. 17 March 2021. n.d."},{"key":"1267_CR69","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1009990","volume":"18","author":"M Aid","year":"2022","unstructured":"Aid M, Vidal SJ, Piedra-Mora C, et al. Ad26.COV2.S prevents upregulation of SARS-CoV-2 induced pathways of inflammation and thrombosis in hamsters and rhesus macaques. PLoS Pathog. 2022;18:e1009990. https:\/\/doi.org\/10.1371\/journal.ppat.1009990.","journal-title":"PLoS Pathog"},{"key":"1267_CR70","doi-asserted-by":"publisher","first-page":"3467","DOI":"10.1016\/j.cell.2021.05.040","volume":"184","author":"X He","year":"2021","unstructured":"He X, Chandrashekar A, Zahn R, et al. Low-dose Ad26.COV2.S protection against SARS-CoV-2 challenge in rhesus macaques. Cell. 2021;184:3467-3473.e11. https:\/\/doi.org\/10.1016\/j.cell.2021.05.040.","journal-title":"Cell"},{"key":"1267_CR71","doi-asserted-by":"publisher","first-page":"2187","DOI":"10.1056\/nejmoa2101544","volume":"384","author":"J Sadoff","year":"2021","unstructured":"Sadoff J, Gray G, Vandebosch A, et al. Safety and efficacy of single-dose Ad26.COV2.S vaccine against Covid-19. N Engl J Med. 2021;384:2187\u2013201. https:\/\/doi.org\/10.1056\/nejmoa2101544.","journal-title":"N Engl J Med"}],"container-title":["The AAPS Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1208\/s12248-026-01267-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1208\/s12248-026-01267-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1208\/s12248-026-01267-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T07:02:38Z","timestamp":1790665358000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1208\/s12248-026-01267-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,19]]},"references-count":71,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["1267"],"URL":"https:\/\/doi.org\/10.1208\/s12248-026-01267-2","relation":{},"ISSN":["1550-7416"],"issn-type":[{"value":"1550-7416","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,19]]},"assertion":[{"value":"17 December 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 June 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 August 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"None related to this manuscript.","order":1,"name":"Ethics","label":"Conflict of interest","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This content has been made available to all.","name":"free","label":"Free to read"}],"article-number":"127"}}