{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:01:22Z","timestamp":1792789282860,"version":"4.5.0"},"reference-count":60,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2023,8,22]],"date-time":"2023-08-22T00:00:00Z","timestamp":1692662400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fondo de Ciencia B\u00e1sica SEP-CONACyT","award":["25480"],"award-info":[{"award-number":["25480"]}]},{"name":"Fondo de Ciencia B\u00e1sica SEP-CONACyT","award":["259096"],"award-info":[{"award-number":["259096"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The development of several vaccines against the SARS-CoV2 virus and their application in millions of people have shown efficacy and safety in the transfer of genes to muscle turning this tissue into a protein-producing factory. Established advanced liver fibrosis, is characterized by replacement of hepatic parenchyma by tissue scar, mostly collagen type I, with increased profibrogenic and proinflammatory molecules gene expression. Matrix metalloproteinase 8 (MMP-8) is an interstitial collagen-degrading proenzyme acting preferentially on collagen type I when activated. This study was carried out to elucidate the effect of an intramuscularly delivered adenoviral vector containing proMMP-8 gene cDNA (AdhMMP8) in male Wistar rats with experimental advanced liver fibrosis induced by thioacetamide. Therapeutic effects were monitored after 1, 2, or 3 weeks of a single dose (3 \u00d7 1011 vp\/kg) of AdhMMP8. Circulating and liver concentration of MMP-8 protein remained constant; hepatic fibrosis decreased up to 48%; proinflammatory and profibrogenic genes expression diminished: TNF-\u03b1 2.28-fold, IL-1 1.95-fold, Col 1A1 4-fold, TGF-\u03b21 3-fold and CTGF 2-fold; and antifibrogenic genes expression raised, MMP-9 2.8-fold and MMP-1 10-fold. Our data proposes that the administration of AdhMMP8 in muscle is safe and effective in achieving liver fibrosis regression at a comparable extent as when the adenoviral vector is delivered systemically to reach the liver, using a minimally invasive procedure.<\/jats:p>","DOI":"10.3390\/cells12172127","type":"journal-article","created":{"date-parts":[[2023,8,22]],"date-time":"2023-08-22T08:58:54Z","timestamp":1692694734000},"page":"2127","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["AdhMMP8 Vector Administration in Muscle: An Alternate Strategy to Regress Hepatic Fibrosis"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3430-9391","authenticated-orcid":false,"given":"Jes\u00fas","family":"Garc\u00eda-Ba\u00f1uelos","sequence":"first","affiliation":[{"name":"Institute for Molecular Biology in Medicine and Gene Therapy, Department of Molecular Biology and Genomics, Health Sciences University Center, University of Guadalajara, Guadalajara 44340, Jalisco, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ed\u00e9n","family":"Oceguera-Contreras","sequence":"additional","affiliation":[{"name":"Laboratorio de Sistemas Biol\u00f3gicos, Centro Universitario de los Valles, Universidad de Guadalajara, Carretera Guadalajara-Ameca km. 45.5, Ameca 46600, Jalisco, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1708-1495","authenticated-orcid":false,"given":"Ana","family":"Sandoval-Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Institute for Molecular Biology in Medicine and Gene Therapy, Department of Molecular Biology and Genomics, Health Sciences University Center, University of Guadalajara, Guadalajara 44340, Jalisco, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Blanca Estela","family":"Bastidas-Ram\u00edrez","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n en Enfermedades Cr\u00f3nico Degenerativas, Department of Molecular Biology and Genomics, Health Sciences University Center, University of Guadalajara, Guadalajara 44340, Jalisco, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Lucano-Landeros","sequence":"additional","affiliation":[{"name":"Institute for Molecular Biology in Medicine and Gene Therapy, Department of Molecular Biology and Genomics, Health Sciences University Center, University of Guadalajara, Guadalajara 44340, Jalisco, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Gordillo-Bastidas","sequence":"additional","affiliation":[{"name":"Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey 64849, Nuevo Leon, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2774-6390","authenticated-orcid":false,"given":"Belinda C.","family":"G\u00f3mez-Meda","sequence":"additional","affiliation":[{"name":"Instituto de Gen\u00e9tica Humana \u201cDr. Enrique Corona Rivera\u201d, Department of Molecular Biology and Genomics, Health Sciences University Center, Guadalajara 44340, Jalisco, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4640-7263","authenticated-orcid":false,"given":"Arturo","family":"Santos","sequence":"additional","affiliation":[{"name":"Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey 64849, Nuevo Leon, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1288-888X","authenticated-orcid":false,"given":"Eira","family":"Cerda-Reyes","sequence":"additional","affiliation":[{"name":"Hospital Central Militar, Mexico City 11600, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7101-9943","authenticated-orcid":false,"given":"Juan","family":"Armendariz-Borunda","sequence":"additional","affiliation":[{"name":"Institute for Molecular Biology in Medicine and Gene Therapy, Department of Molecular Biology and Genomics, Health Sciences University Center, University of Guadalajara, Guadalajara 44340, Jalisco, Mexico"},{"name":"Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey 64849, Nuevo Leon, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1056\/NEJMoa2035389","article-title":"Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine","volume":"384","author":"Baden","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2603","DOI":"10.1056\/NEJMoa2034577","article-title":"Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine","volume":"383","author":"Polack","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2187","DOI":"10.1056\/NEJMoa2101544","article-title":"Safety and Efficacy of Single-Dose Ad26.COV2.S Vaccine against Covid-19","volume":"384","author":"Sadoff","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1465","DOI":"10.1126\/science.1690918","article-title":"Direct gene transfer into mouse muscle in vivo","volume":"247","author":"Wolff","year":"1990","journal-title":"Science"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1677\/joe.0.1620001","article-title":"Using skeletal muscle as an artificial endocrine tissue","volume":"162","author":"MacColl","year":"1999","journal-title":"J. Endocrinol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1038\/nm0497-429","article-title":"Gene therapy of murine motor neuron disease using adenoviral vectors for neurotrophic factors","volume":"3","author":"Haase","year":"1997","journal-title":"Nat. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1016\/j.jhep.2023.03.017","article-title":"Global burden of liver disease: 2023 update","volume":"79","author":"Devarbhavi","year":"2023","journal-title":"J. Hepatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1097\/MOG.0000000000000524","article-title":"Fibrosis reversal after hepatitis C virus elimination","volume":"35","author":"Rockey","year":"2019","journal-title":"Curr. Opin. Gastroenterol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1502","DOI":"10.1053\/j.gastro.2020.09.065","article-title":"Fibrosis Regression after Eradication of Hepatitis C Virus: From Bench to Bedside","volume":"160","author":"Rockey","year":"2021","journal-title":"Gastroenterology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1120","DOI":"10.4254\/wjh.v14.i6.1120","article-title":"Fibrosis regression following hepatitis C antiviral therapy","volume":"14","author":"Elsharkawy","year":"2022","journal-title":"World J. Hepatol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1038\/s41598-021-03272-1","article-title":"Regression of liver fibrosis and hepatocellular carcinoma development after HCV eradication with oral antiviral agents","volume":"12","author":"Yoo","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"189","DOI":"10.4132\/jptm.2023.05.24","article-title":"A review of liver fibrosis and cirrhosis regression","volume":"57","author":"Lee","year":"2023","journal-title":"J. Pathol. Transl. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1016\/S0140-6736(21)01374-X","article-title":"Liver cirrhosis","volume":"398","author":"Krag","year":"2021","journal-title":"Lancet"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Zhang, D., Zhang, Y., and Sun, B. (2022). The Molecular Mechanisms of Liver Fibrosis and Its Potential Therapy in Application. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232012572"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1146\/annurev-pathol-011110-130246","article-title":"Pathogenesis of Liver Fibrosis","volume":"6","author":"Friedman","year":"2011","journal-title":"Annu. Rev. Pathol. Mech. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1172\/JCI115850","article-title":"Human hepatic lipocytes synthesize tissue inhibitor of metalloproteinases-1. Implications for regulation of matrix degradation in liver","volume":"90","author":"Iredale","year":"1992","journal-title":"J. Clin. Invest."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/0009-8981(93)90221-O","article-title":"Serum tissue inhibitor of metalloproteinases in patients with chronic liver disease and with hepatocellular carcinoma","volume":"218","author":"Murawaki","year":"1993","journal-title":"Clin. Chim. Acta"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1002\/hep.510300335","article-title":"Gene therapy for hepatic fibrosis-bringing treatment into the new millennium","volume":"30","author":"Rockey","year":"1999","journal-title":"Hepatology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.cytogfr.2006.04.001","article-title":"Matrix metalloproteinase-8: Cleavage can be decisive","volume":"17","author":"Libert","year":"2006","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1038\/nri3499","article-title":"Metalloproteinases and their natural inhibitors in inflammation and immunity","volume":"13","author":"Khokha","year":"2013","journal-title":"Nat. Rev. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1940","DOI":"10.1016\/j.bbamcr.2017.04.015","article-title":"Matrix metalloproteinase collagenolysis in health and disease","volume":"1864","author":"Amar","year":"2017","journal-title":"Biochim. Biophys. Acta Mol. Cell Res."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Laronha, H., and Caldeira, J. (2020). Structure and Function of Human Matrix Metalloproteinases. Cells, 9.","DOI":"10.3390\/cells9051076"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1038\/s41575-020-00372-7","article-title":"Molecular and cellular mechanisms of liver fibrosis and its regression","volume":"18","author":"Kisseleva","year":"2021","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1038\/5593","article-title":"Hepatocyte growth factor gene therapy of liver cirrhosis in rats","volume":"5","author":"Ueki","year":"1999","journal-title":"Nat. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1016\/S0168-8278(00)80307-4","article-title":"Truncated active matrix metalloproteinase-8 gene expression in HepG2 cells is active against native type I collagen","volume":"33","author":"Hasty","year":"2000","journal-title":"J. Hepatol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1006\/mthe.2000.0210","article-title":"Liver cirrhosis is reverted by urokinase-type plasminogen activator gene therapy","volume":"2","author":"Salgado","year":"2000","journal-title":"Mol. Ther."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1038\/sj.gt.3301647","article-title":"Cirrhotic rat livers with extensive fibrosis can be safely transduced with clinical-grade adenoviral vectors. Evidence of cirrhosis reversion","volume":"9","author":"Miranda","year":"2002","journal-title":"Gene Ther."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1053\/j.gastro.2003.12.045","article-title":"Treatment with human metalloproteinase-8 gene delivery ameliorates experimental rat liver cirrhosis","volume":"126","author":"Sandoval","year":"2004","journal-title":"Gastroenterology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1038\/gt.2010.107","article-title":"Combinatorial gene therapy induces regression of hepatic encephalopathy","volume":"18","year":"2011","journal-title":"Gene Ther."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Meza-R\u00edos, A., Garc\u00eda-Benavides, L., Garc\u00eda-Ba\u00f1uelos, J., Salazar-Montes, A., Armend\u00e1riz-Borunda, J., and Sandoval-Rodr\u00edguez, A. (2016). Simultaneous Administration of ADSCs-Based Therapy and Gene Therapy Using Ad-huPA Reduces Experimental Liver Fibrosis. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0166849"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1007\/s12033-018-0066-7","article-title":"Interferon-\u03b1 Silencing by Small Interference RNA Increases Adenovirus Transduction and Transgene Expression in Huh7 Cells","volume":"60","year":"2018","journal-title":"Mol. Biotechnol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"878161","DOI":"10.3389\/fpubh.2022.878161","article-title":"Human Adenovirus Associated Hepatic Injury","volume":"10","author":"Zheng","year":"2022","journal-title":"Front. Public Health"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1016\/j.jcyt.2021.07.013","article-title":"Adenovirus vector-attributed hepatotoxicity blocks clinical application in gene therapy","volume":"23","author":"Wang","year":"2021","journal-title":"Cytotherapy"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/j.jcmgh.2023.05.010","article-title":"In Vivo and In Vitro Models to Study Liver Fibrosis: Mechanisms and Limitations","volume":"16","author":"Lee","year":"2023","journal-title":"Cell Mol. Gastroenterol. Hepatol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/j.jbiosc.2011.07.018","article-title":"Production of first generation adenoviral vectors for preclinical protocols: Amplification, purification and functional titration","volume":"112","year":"2011","journal-title":"J. Biosci. Bioeng."},{"key":"ref_36","first-page":"1877","article-title":"Saturation toxicokinetics of thioacetamide: Role in initiation of liver injury","volume":"33","author":"Chilakapati","year":"2005","journal-title":"Drug Metab. Dispos."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1159\/000129007","article-title":"Thioacetamide- and carbon tetrachloride-induced liver cirrhosis","volume":"21","author":"Dashti","year":"1989","journal-title":"Eur. Surg Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1016\/S0168-8278(02)00011-9","article-title":"Reproducible production of thioacetamide-induced macronodular cirrhosis in the rat with no mortality","volume":"36","author":"Li","year":"2002","journal-title":"J. Hepatol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/0003-2697(87)90021-2","article-title":"Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction","volume":"162","author":"Chomczynski","year":"1987","journal-title":"Anal Biochem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2-[Delta][Delta] CT method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1186\/1471-2105-7-85","article-title":"Statistical analysis of real-time PCR data","volume":"7","author":"Yuan","year":"2006","journal-title":"BMC Bioinform."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1096\/fj.04-3180fje","article-title":"Green fluorescent protein is a quantitative reporter of gene expression in individual eukaryotic cells","volume":"19","author":"Soboleski","year":"2005","journal-title":"FASEB J."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1089\/10430340050016139","article-title":"A soluble transforming growth factor beta receptor expressed in muscle prevents liver fibrogenesis and dysfunction in rats","volume":"11","author":"Ueno","year":"2000","journal-title":"Hum. Gene Ther."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1042\/bj2370853","article-title":"Proactivator-dependent activation of procollagenase induced by treatment with EGTA","volume":"237","author":"Vater","year":"1986","journal-title":"Biochem J."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1874","DOI":"10.1126\/science.312.5782.1874b","article-title":"Role of iNOS in human host defense","volume":"312","author":"Nathan","year":"2006","journal-title":"Science"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"11557","DOI":"10.1073\/pnas.91.24.11557","article-title":"Stable delivery of physiologic levels of recombinant erythropoietin to the systemic circulation by intramuscular injection of replication-defective adenovirus","volume":"91","author":"Tripathy","year":"1994","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1161\/01.RES.0000070112.80711.3D","article-title":"Matrix metalloproteinases and tissue inhibitors of metalloproteinases: Structure, function, and biochemistry","volume":"2","author":"Visse","year":"2003","journal-title":"Circ. Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1007\/s11095-007-9311-7","article-title":"Matrix Metalloproteinase Gene Delivery for Liver Fibrosis","volume":"25","author":"Iimuro","year":"2008","journal-title":"Pharm. Res."},{"key":"ref_49","first-page":"386","article-title":"Thioacetamide-induced hepatic necrosis. II. Pharmacokinetics of thioacetamide and thioacetamide-S-oxide in the rat","volume":"208","author":"Porter","year":"1979","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1002\/hep.1840090326","article-title":"Problems with animal models of chronic liver disease: Suggestions for improvement in standardization","volume":"9","author":"Mullen","year":"1989","journal-title":"Hepatology"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1177\/0148607195019006461","article-title":"Dietary long-chain polyunsaturated fatty acids influence the recovery of thioacetamide-induced liver cirrhosis in rats","volume":"19","author":"Moreira","year":"1995","journal-title":"JPEN J. Parenter. Enteral. Nutr."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1002\/hep.510240220","article-title":"Population of hepatic macrophages and response of perfused liver to platelet-activating factor during production of thioacetamide-induced cirrhosis in rats","volume":"24","author":"Noda","year":"1996","journal-title":"Hepatology"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1016\/S0076-6879(81)80054-7","article-title":"Mammalian collagenases","volume":"80 Pt C","author":"Cawston","year":"1981","journal-title":"Methods Enzymol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1046\/j.1523-1755.1998.00975.x","article-title":"Cloning of murine membrane-type-1-matrix metalloproteinase (MT-1-MMP) and its metanephric developmental regulation with respect to MMP-2 and its inhibitor","volume":"54","author":"Ota","year":"1998","journal-title":"Kidney Int."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1096\/fj.02-0494fje","article-title":"Mutation in collagen-1 that confers resistance to the action of collagenase results in failure of recovery from CCl4-induced liver fibrosis, persistence of activated hepatic stellate cells, and diminished hepatocyte regeneration","volume":"17","author":"Issa","year":"2003","journal-title":"FASEB J."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Liu, J., Cheng, X., Guo, Z., Wang, Z., Li, D., Kang, F., Li, H., Li, B., Cao, Z., and Nassal, M. (2013). Truncated Active Human Matrix Metalloproteinase-8 Delivered by a Chimeric Adenovirus-Hepatitis B Virus Vector Ameliorates Rat Liver Cirrhosis. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0053392"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"5579","DOI":"10.1016\/j.vaccine.2016.09.043","article-title":"Prevalence of serum neutralizing antibodies to adenovirus type 5 (Ad5) and 41 (Ad41) in children is associated with age and sanitary conditions","volume":"34","author":"Yang","year":"2016","journal-title":"Vaccine"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"909","DOI":"10.3389\/fimmu.2020.00909","article-title":"Factors Which Contribute to the Immunogenicity of Non-replicating Adenoviral Vectored Vaccines","volume":"11","author":"Coughlan","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/S0140-6736(21)00234-8","article-title":"Safety and efficacy of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine: An interim analysis of a randomised controlled phase 3 trial in Russia","volume":"397","author":"Logunov","year":"2021","journal-title":"Lancet"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/S0140-6736(20)31605-6","article-title":"Immunogenicity and safety of a recombinant adenovirus type-5-vectored COVID-19 vaccine in healthy adults aged 18 years or older: A randomised, double-blind, placebo-controlled, phase 2 trial","volume":"396","author":"Zhu","year":"2020","journal-title":"Lancet"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/17\/2127\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:39:36Z","timestamp":1760128776000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/17\/2127"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,22]]},"references-count":60,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2023,9]]}},"alternative-id":["cells12172127"],"URL":"https:\/\/doi.org\/10.3390\/cells12172127","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,22]]}}}