{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T14:43:03Z","timestamp":1785508983693,"version":"3.56.0"},"reference-count":37,"publisher":"Elsevier BV","issue":"1","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2027,1,7]],"date-time":"2027-01-07T00:00:00Z","timestamp":1799280000000},"content-version":"am","delay-in-days":371,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 HL147570"],"award-info":[{"award-number":["R01 HL147570"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007557","name":"California Institute of Regenerative Medicine","doi-asserted-by":"publisher","award":["CLIN1-14874"],"award-info":[{"award-number":["CLIN1-14874"]}],"id":[{"id":"10.13039\/100007557","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007557","name":"California Institute of Regenerative Medicine","doi-asserted-by":"publisher","award":["EDUC4-12751"],"award-info":[{"award-number":["EDUC4-12751"]}],"id":[{"id":"10.13039\/100007557","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart Lung and Blood Institute","doi-asserted-by":"publisher","award":["R01 HL164896"],"award-info":[{"award-number":["R01 HL164896"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart Lung and Blood Institute","doi-asserted-by":"publisher","award":["R01 HL135866"],"award-info":[{"award-number":["R01 HL135866"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000900","name":"California Institute for Regenerative Medicine","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000900","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["940033"],"award-info":[{"award-number":["940033"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["24IPA1275047"],"award-info":[{"award-number":["24IPA1275047"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Molecular Therapy"],"published-print":{"date-parts":[[2026,1]]},"DOI":"10.1016\/j.ymthe.2025.10.037","type":"journal-article","created":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T23:29:04Z","timestamp":1760657344000},"page":"131-139","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":2,"title":["Biological pacemaker induced by focal cardiac transduction with AAV-TBX18"],"prefix":"10.1016","volume":"34","author":[{"given":"Rodrigo","family":"Miguel-dos-Santos","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James Frederick","family":"Dawkins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thassio","family":"Mesquita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lizbeth","family":"Sanchez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Fournier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo","family":"Marb\u00e1n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5939-8111","authenticated-orcid":false,"given":"Eugenio","family":"Cingolani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ymthe.2025.10.037_bib1","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1001\/jamacardio.2022.5526","article-title":"Prevalence and Prognostic Significance of Bradyarrhythmias in Patients Screened for Atrial Fibrillation vs Usual Care: Post Hoc Analysis of the LOOP Randomized Clinical Trial","volume":"8","author":"Diederichsen","year":"2023","journal-title":"JAMA Cardiol."},{"key":"10.1016\/j.ymthe.2025.10.037_bib2","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1016\/j.jacc.2018.10.043","volume":"74","author":"Kusumoto","year":"2019","journal-title":"J. Am. Coll. Cardiol."},{"key":"10.1016\/j.ymthe.2025.10.037_bib3","doi-asserted-by":"crossref","first-page":"e201","DOI":"10.1161\/CIR.0000000000001187","article-title":"Update on Cardiovascular Implantable Electronic Device Infections and Their Prevention, Diagnosis, and Management: A Scientific Statement From the American Heart Association: Endorsed by the International Society for Cardiovascular Infectious Diseases","volume":"149","author":"Baddour","year":"2024","journal-title":"Circulation"},{"key":"10.1016\/j.ymthe.2025.10.037_bib4","doi-asserted-by":"crossref","DOI":"10.1161\/CIRCEP.124.013070","article-title":"Incidence and Predictors of Pacing-Induced Right Ventricular Cardiomyopathy","volume":"17","author":"Boyle","year":"2024","journal-title":"Circ. Arrhythm. Electrophysiol."},{"key":"10.1016\/j.ymthe.2025.10.037_bib5","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1016\/j.ahj.2007.12.022","article-title":"Temporal trends in permanent pacemaker implantation: a population-based study","volume":"155","author":"Uslan","year":"2008","journal-title":"Am. Heart J."},{"key":"10.1016\/j.ymthe.2025.10.037_bib6","doi-asserted-by":"crossref","first-page":"1540","DOI":"10.1016\/j.jacc.2012.07.017","article-title":"Trends in permanent pacemaker implantation in the United States from 1993 to 2009: increasing complexity of patients and procedures","volume":"60","author":"Greenspon","year":"2012","journal-title":"J. Am. Coll. Cardiol."},{"key":"10.1016\/j.ymthe.2025.10.037_bib7","doi-asserted-by":"crossref","DOI":"10.1136\/openhrt-2014-000177","article-title":"Trends in the incidence and prevalence of cardiac pacemaker insertions in an ageing population","volume":"1","author":"Bradshaw","year":"2014","journal-title":"Open Heart"},{"key":"10.1016\/j.ymthe.2025.10.037_bib8","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1038\/419132b","article-title":"Biological pacemaker created by gene transfer","volume":"419","author":"Miake","year":"2002","journal-title":"Nature"},{"key":"10.1016\/j.ymthe.2025.10.037_bib9","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1038\/nrcardio.2017.165","article-title":"Next-generation pacemakers: from small devices to biological pacemakers","volume":"15","author":"Cingolani","year":"2018","journal-title":"Nat. Rev. Cardiol."},{"key":"10.1016\/j.ymthe.2025.10.037_bib10","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1161\/CIRCRESAHA.123.323180","article-title":"Biological Pacemakers: Present and Future","volume":"134","author":"Mesquita","year":"2024","journal-title":"Circ. Res."},{"key":"10.1016\/j.ymthe.2025.10.037_bib11","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1038\/nbt.2465","article-title":"Direct conversion of quiescent cardiomyocytes to pacemaker cells by expression of Tbx18","volume":"31","author":"Kapoor","year":"2013","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.ymthe.2025.10.037_bib12","doi-asserted-by":"crossref","first-page":"245ra94","DOI":"10.1126\/scitranslmed.3008681","article-title":"Biological pacemaker created by minimally invasive somatic reprogramming in pigs with complete heart block","volume":"6","author":"Hu","year":"2014","journal-title":"Sci. Transl. Med."},{"key":"10.1016\/j.ymthe.2025.10.037_bib13","doi-asserted-by":"crossref","DOI":"10.3390\/ijms242216519","article-title":"Adenoviral Gene Therapy Vectors in Clinical Use-Basic Aspects with a Special Reference to Replication-Competent Adenovirus Formation and Its Impact on Clinical Safety","volume":"24","author":"Leikas","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.ymthe.2025.10.037_bib14","article-title":"MicroRNA-dependent suppression of biological pacemaker activity induced by TBX18","volume":"3","author":"Sanchez","year":"2022","journal-title":"Cell Rep. Med."},{"key":"10.1016\/j.ymthe.2025.10.037_bib15","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1038\/s41551-024-01211-9","article-title":"Transient pacing in pigs with complete heart block via myocardial injection of mRNA coding for the T-box transcription factor 18","volume":"8","author":"Wolfson","year":"2024","journal-title":"Nat. Biomed. Eng."},{"key":"10.1016\/j.ymthe.2025.10.037_bib16","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1038\/s41392-024-01780-w","article-title":"Adeno-associated virus as a delivery vector for gene therapy of human diseases","volume":"9","author":"Wang","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"10.1016\/j.ymthe.2025.10.037_bib17","doi-asserted-by":"crossref","first-page":"3311","DOI":"10.1182\/blood-2010-08-302729","article-title":"Assessing the potential for AAV vector genotoxicity in a murine model","volume":"117","author":"Li","year":"2011","journal-title":"Blood"},{"key":"10.1016\/j.ymthe.2025.10.037_bib18","doi-asserted-by":"crossref","DOI":"10.1002\/jgm.3015","article-title":"Gene therapy clinical trials worldwide to 2017: An update","volume":"20","author":"Ginn","year":"2018","journal-title":"J. Gene Med."},{"key":"10.1016\/j.ymthe.2025.10.037_bib19","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1038\/4743","article-title":"Long-term correction of canine hemophilia B by gene transfer of blood coagulation factor IX mediated by adeno-associated viral vector","volume":"5","author":"Herzog","year":"1999","journal-title":"Nat. Med."},{"key":"10.1016\/j.ymthe.2025.10.037_bib20","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1038\/nbt1073","article-title":"Adeno-associated virus serotype 8 efficiently delivers genes to muscle and heart","volume":"23","author":"Wang","year":"2005","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.ymthe.2025.10.037_bib21","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1089\/humc.2017.010","article-title":"Persistent Expression of Dopamine-Synthesizing Enzymes 15 Years After Gene Transfer in a Primate Model of Parkinson\u2019s Disease","volume":"28","author":"Sehara","year":"2017","journal-title":"Hum. Gene Ther. Clin. Dev."},{"key":"10.1016\/j.ymthe.2025.10.037_bib22","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1038\/s41392-021-00487-6","article-title":"Viral vector platforms within the gene therapy landscape","volume":"6","author":"Bulcha","year":"2021","journal-title":"Sig Transduct Target Ther."},{"key":"10.1016\/j.ymthe.2025.10.037_bib23","doi-asserted-by":"crossref","DOI":"10.3389\/fphys.2022.977807","article-title":"Adenosine reduces sinoatrial node cell action potential firing rate by uncoupling its membrane and calcium clocks","volume":"13","author":"Wirth","year":"2022","journal-title":"Front. Physiol."},{"key":"10.1016\/j.ymthe.2025.10.037_bib24","doi-asserted-by":"crossref","first-page":"6930","DOI":"10.1038\/s41598-019-43300-9","article-title":"A rat model of complete atrioventricular block recapitulates clinical indices of bradycardia and provides a platform to test disease-modifying therapies","volume":"9","author":"Kim","year":"2019","journal-title":"Sci. Rep."},{"key":"10.1016\/j.ymthe.2025.10.037_bib25","doi-asserted-by":"crossref","first-page":"3009","DOI":"10.1111\/jce.14733","article-title":"Sensors for rate-adaptive pacing: How they work, strengths, and limitations","volume":"31","author":"Trohman","year":"2020","journal-title":"J. Cardiovasc. Electrophysiol."},{"key":"10.1016\/j.ymthe.2025.10.037_bib26","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.3390\/s23031427","article-title":"Rate-Responsive Cardiac Pacing: Technological Solutions and Their Applications","volume":"23","author":"\u015awier\u017cy\u0144ska","year":"2023","journal-title":"Sensors (Basel)"},{"key":"10.1016\/j.ymthe.2025.10.037_bib27","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.130532","article-title":"Region-specific parasympathetic nerve remodeling in the left atrium contributes to creation of a vulnerable substrate for atrial fibrillation","volume":"4","author":"Gussak","year":"2019","journal-title":"JCI Insight"},{"key":"10.1016\/j.ymthe.2025.10.037_bib28","article-title":"Sympathetic Nervous System Mediates Cardiac Remodeling After Myocardial Infarction in a Circadian Disruption Model","volume":"8","author":"Wang","year":"2021","journal-title":"Front. Cardiovasc. Med."},{"key":"10.1016\/j.ymthe.2025.10.037_bib29","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1161\/CIRCRESAHA.113.302549","article-title":"Role of the autonomic nervous system in modulating cardiac arrhythmias","volume":"114","author":"Shen","year":"2014","journal-title":"Circ. Res."},{"key":"10.1016\/j.ymthe.2025.10.037_bib30","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.1016\/j.hrthm.2012.04.020","article-title":"Biological pacemaker created by percutaneous gene delivery via venous catheters in a porcine model of complete heart block","volume":"9","author":"Cingolani","year":"2012","journal-title":"Heart Rhythm"},{"key":"10.1016\/j.ymthe.2025.10.037_bib31","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1161\/CIRCULATIONAHA.106.617613","article-title":"Wild-type and mutant HCN channels in a tandem biological-electronic cardiac pacemaker","volume":"114","author":"Bucchi","year":"2006","journal-title":"Circulation"},{"key":"10.1016\/j.ymthe.2025.10.037_bib32","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1016\/j.jacc.2012.12.031","article-title":"HCN2\/SkM1 gene transfer into canine left bundle branch induces stable, autonomically responsive biological pacing at physiological heart rates","volume":"61","author":"Boink","year":"2013","journal-title":"J. Am. Coll. Cardiol."},{"key":"10.1016\/j.ymthe.2025.10.037_bib33","doi-asserted-by":"crossref","first-page":"1673","DOI":"10.1016\/j.jacc.2018.12.086","article-title":"Antegrade Conduction Rescues Right Ventricular Pacing-Induced Cardiomyopathy in Complete Heart Block","volume":"73","author":"Dawkins","year":"2019","journal-title":"J. Am. Coll. Cardiol."},{"key":"10.1016\/j.ymthe.2025.10.037_bib34","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1161\/CIRCEP.113.000311","article-title":"Principles of cardiac electric propagation and their implications for re-entrant arrhythmias","volume":"6","author":"Spector","year":"2013","journal-title":"Circ. Arrhythm. Electrophysiol."},{"key":"10.1016\/j.ymthe.2025.10.037_bib35","doi-asserted-by":"crossref","first-page":"2575","DOI":"10.1016\/j.jacc.2014.09.056","article-title":"Engineered electrical conduction tract restores conduction in complete heart block: from in vitro to in vivo proof of concept","volume":"64","author":"Cingolani","year":"2014","journal-title":"J. Am. Coll. Cardiol."},{"key":"10.1016\/j.ymthe.2025.10.037_bib36","doi-asserted-by":"crossref","DOI":"10.1002\/advs.201901099","article-title":"Engineered Cardiac Pacemaker Nodes Created by TBX18 Gene Transfer Overcome Source-Sink Mismatch","volume":"6","author":"Grijalva","year":"2019","journal-title":"Adv. Sci."},{"key":"10.1016\/j.ymthe.2025.10.037_bib37","doi-asserted-by":"crossref","DOI":"10.1016\/j.omtm.2023.101124","article-title":"The hunt for novel AAV capsids with improved cardiac tropism","volume":"31","author":"Miguel-Dos-Santos","year":"2023","journal-title":"Mol. Ther. Methods Clin. Dev."}],"container-title":["Molecular Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1525001625008585?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1525001625008585?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T19:34:40Z","timestamp":1783020880000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1525001625008585"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":37,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["S1525001625008585"],"URL":"https:\/\/doi.org\/10.1016\/j.ymthe.2025.10.037","relation":{},"ISSN":["1525-0016"],"issn-type":[{"value":"1525-0016","type":"print"}],"subject":[],"published":{"date-parts":[[2026,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Biological pacemaker induced by focal cardiac transduction with AAV-TBX18","name":"articletitle","label":"Article Title"},{"value":"Molecular Therapy","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ymthe.2025.10.037","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}]}}