{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T17:32:02Z","timestamp":1793640722862,"version":"4.5.1"},"reference-count":116,"publisher":"Elsevier BV","issue":"5","license":[{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T00:00:00Z","timestamp":1769385600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007806","name":"Mass General Brigham Inc","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007806","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","onlinecjc.ca","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Canadian Journal of Cardiology"],"published-print":{"date-parts":[[2026,5]]},"DOI":"10.1016\/j.cjca.2026.01.035","type":"journal-article","created":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T15:38:44Z","timestamp":1769701124000},"page":"905-916","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Past, Present, and Future of Cardiac Gene Therapy"],"prefix":"10.1016","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2522-1507","authenticated-orcid":false,"given":"Roger J.","family":"Hajjar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.cjca.2026.01.035_bib1","first-page":"e41","article-title":"2025 Heart disease and stroke statistics: a report of US and global data from the American Heart Association","volume":"151","author":"Martin","year":"2025","journal-title":"Circulation"},{"key":"10.1016\/j.cjca.2026.01.035_bib2","doi-asserted-by":"crossref","first-page":"1843","DOI":"10.1093\/cvr\/cvaf109","article-title":"Gene therapy in cardiac and vascular diseases: a review of approaches to treat genetic and common cardiovascular diseases with novel gene-based therapeutics","volume":"121","author":"Musolino","year":"2025","journal-title":"Cardiovasc Res"},{"key":"10.1016\/j.cjca.2026.01.035_bib3","doi-asserted-by":"crossref","first-page":"1651","DOI":"10.1093\/eurheartj\/ehw019","article-title":"Gene therapy for the treatment of heart failure: promise postponed","volume":"37","author":"Hulot","year":"2016","journal-title":"Eur Heart J"},{"key":"10.1016\/j.cjca.2026.01.035_bib4","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1161\/CIRCRESAHA.116.310039","article-title":"Introducing genes to the heart: all about delivery","volume":"120","author":"Hajjar","year":"2017","journal-title":"Circ Res"},{"key":"10.1016\/j.cjca.2026.01.035_bib5","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1161\/CIRCRESAHA.118.311587","article-title":"Human cardiac gene therapy","volume":"123","author":"Ishikawa","year":"2018","journal-title":"Circ Res"},{"key":"10.1016\/j.cjca.2026.01.035_bib6","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1172\/JCI62837","article-title":"Potential of gene therapy as a treatment for heart failure","volume":"123","author":"Hajjar","year":"2013","journal-title":"J Clin Invest"},{"key":"10.1016\/j.cjca.2026.01.035_bib7","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1161\/01.RES.86.6.616","article-title":"Prospects for gene therapy for heart failure","volume":"86","author":"Hajjar","year":"2000","journal-title":"Circ Res"},{"issue":"suppl 1","key":"10.1016\/j.cjca.2026.01.035_bib8","first-page":"65","article-title":"Arterial gene therapy: a molecular biological perspective for the treatment of arterial ischemia","volume":"86","author":"Asahara","year":"1997","journal-title":"Z Kardiol"},{"issue":"suppl","key":"10.1016\/j.cjca.2026.01.035_bib9","doi-asserted-by":"crossref","first-page":"63S","DOI":"10.1016\/S0002-9149(98)00764-4","article-title":"Vascular endothelial growth factor: gene therapy and therapeutic angiogenesis","volume":"82","author":"Isner","year":"1998","journal-title":"Am J Cardiol"},{"issue":"suppl","key":"10.1016\/j.cjca.2026.01.035_bib10","doi-asserted-by":"crossref","first-page":"S132","DOI":"10.1016\/S0002-8703(99)70333-9","article-title":"Gene therapy for myocardial angiogenesis","volume":"138","author":"Losordo","year":"1999","journal-title":"Am Heart J"},{"key":"10.1016\/j.cjca.2026.01.035_bib11","doi-asserted-by":"crossref","first-page":"1178","DOI":"10.1016\/S0140-6736(16)00082-9","article-title":"Calcium Upregulation by Percutaneous Administration of Gene Therapy in Patients in Cardiac Disease (CUPID 2): a randomised, multinational, double-blind, placebo-controlled, phase 2b trial","volume":"387","author":"Greenberg","year":"2016","journal-title":"Lancet"},{"key":"10.1016\/j.cjca.2026.01.035_bib12","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.cardfail.2009.01.013","article-title":"Calcium Upregulation by Percutaneous Administration of Gene Therapy in Cardiac Disease (CUPID trial), a first-in-human phase 1\/2 clinical trial","volume":"15","author":"Jaski","year":"2009","journal-title":"J Card Fail"},{"key":"10.1016\/j.cjca.2026.01.035_bib13","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1161\/CIRCULATIONAHA.111.022889","article-title":"Calcium Upregulation by Percutaneous Administration of Gene Therapy in Cardiac Disease (CUPID): a phase 2 trial of intracoronary gene therapy of sarcoplasmic reticulum Ca2+-ATPase in patients with advanced heart failure","volume":"124","author":"Jessup","year":"2011","journal-title":"Circulation"},{"key":"10.1016\/j.cjca.2026.01.035_bib14","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1161\/CIRCRESAHA.113.302421","article-title":"Long-term effects of AAV1\/SERCA2a gene transfer in patients with severe heart failure: analysis of recurrent cardiovascular events and mortality","volume":"114","author":"Zsebo","year":"2014","journal-title":"Circ Res"},{"key":"10.1016\/j.cjca.2026.01.035_bib15","doi-asserted-by":"crossref","first-page":"1534","DOI":"10.1002\/ejhf.826","article-title":"Effect of intracoronary administration of AAV1\/SERCA2a on ventricular remodelling in patients with advanced systolic heart failure: results from the AGENT-HF randomized phase 2 trial","volume":"19","author":"Hulot","year":"2017","journal-title":"Eur J Heart Fail"},{"key":"10.1016\/j.cjca.2026.01.035_bib16","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1038\/s41434-020-0171-7","article-title":"Investigation of the safety and feasibility of AAV1\/SERCA2a gene transfer in patients with chronic heart failure supported with a left ventricular assist device---the SERCA-LVAD trial","volume":"27","author":"Lyon","year":"2020","journal-title":"Gene Ther"},{"key":"10.1016\/j.cjca.2026.01.035_bib17","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1056\/NEJMc1715769","article-title":"Therapy for spinal muscular atrophy","volume":"378","author":"Finkel","year":"2018","journal-title":"N Engl J Med"},{"key":"10.1016\/j.cjca.2026.01.035_bib18","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.1056\/NEJMoa1706198","article-title":"Single-dose gene-replacement therapy for spinal muscular atrophy","volume":"377","author":"Mendell","year":"2017","journal-title":"N Engl J Med"},{"key":"10.1016\/j.cjca.2026.01.035_bib19","doi-asserted-by":"crossref","DOI":"10.1136\/heartjnl-2024-325280","article-title":"Ribonucleic acid and gene therapies in cardiovascular disease: clinical applications, delivery challenges and emerging precision tools [epub ahead of print]","author":"Jordan","year":"2025","journal-title":"Heart"},{"key":"10.1016\/j.cjca.2026.01.035_bib20","doi-asserted-by":"crossref","first-page":"2119","DOI":"10.1056\/NEJMoa2511778","article-title":"Phase 1 trial of CRISPR-Cas9 gene editing targeting ANGPTL3","volume":"393","author":"Laffin","year":"2025","journal-title":"N Engl J Med"},{"key":"10.1016\/j.cjca.2026.01.035_bib21","doi-asserted-by":"crossref","DOI":"10.1097\/CRD.0000000000001076","article-title":"CRISPR\/Cas9-based gene editing for correcting inherited channelopathies [epub ahead of print]","author":"Tran","year":"2025","journal-title":"Cardiol Rev"},{"key":"10.1016\/j.cjca.2026.01.035_bib22","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1186\/s12974-025-03569-2","article-title":"AAV-mediated delivery of a proliferation inducing ligand (APRIL) to cortical neurons limits inflammation and demyelination in the corpus callosum of the cuprizone mouse model","volume":"22","author":"Ricciardi","year":"2025","journal-title":"J Neuroinflamm"},{"key":"10.1016\/j.cjca.2026.01.035_bib23","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1097\/00000658-199509000-00002","article-title":"Gene transfer to the thymus. A means of abrogating the immune response to recombinant adenovirus","volume":"222","author":"DeMatteo","year":"1995","journal-title":"Ann Surg"},{"key":"10.1016\/j.cjca.2026.01.035_bib24","doi-asserted-by":"crossref","first-page":"2060","DOI":"10.1016\/j.jaip.2021.02.006","article-title":"Ten years of newborn screening for severe combined immunodeficiency (SCID) in Massachusetts","volume":"9","author":"Hale","year":"2021","journal-title":"J Allergy Clin Immunol Pract"},{"key":"10.1016\/j.cjca.2026.01.035_bib25","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1034\/j.1600-065X.2000.17806.x","article-title":"Gene therapy of severe combined immunodeficiencies","volume":"178","author":"Fischer","year":"2000","journal-title":"Immunol Rev"},{"key":"10.1016\/j.cjca.2026.01.035_bib26","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1016\/S0002-9149(03)00661-1","article-title":"One-year follow-up of direct myocardial gene transfer of vascular endothelial growth factor-2 using naked plasmid deoxyribonucleic acid by way of thoracotomy in no-option patients","volume":"92","author":"Fortuin","year":"2003","journal-title":"Am J Cardiol"},{"key":"10.1016\/j.cjca.2026.01.035_bib27","doi-asserted-by":"crossref","first-page":"54","DOI":"10.7326\/0003-4819-136-1-200201010-00011","article-title":"Therapeutic angiogenesis for coronary artery disease","volume":"136","author":"Freedman","year":"2002","journal-title":"Ann Intern Med"},{"key":"10.1016\/j.cjca.2026.01.035_bib28","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1038\/415234a","article-title":"Myocardial gene therapy","volume":"415","author":"Isner","year":"2002","journal-title":"Nature"},{"key":"10.1016\/j.cjca.2026.01.035_bib29","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1111\/j.1540-8183.2001.tb00367.x","article-title":"Therapeutic angiogenesis in critical limb and myocardial ischemia","volume":"14","author":"Vale","year":"2001","journal-title":"J Interv Cardiol"},{"key":"10.1016\/j.cjca.2026.01.035_bib30","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1007\/s00109-005-0031-3","article-title":"Intramuscular gene transfer of fibroblast growth factor-1 using improved pCOR plasmid design stimulates collateral formation in a rabbit ischemic hindlimb model","volume":"84","author":"Witzenbichler","year":"2006","journal-title":"J Mol Med (Berl)"},{"key":"10.1016\/j.cjca.2026.01.035_bib31","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1161\/01.CIR.95.2.423","article-title":"Physiological effects of adenoviral gene transfer of sarcoplasmic reticulum calcium ATPase in isolated rat myocytes","volume":"95","author":"Hajjar","year":"1997","journal-title":"Circulation"},{"key":"10.1016\/j.cjca.2026.01.035_bib32","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1161\/01.RES.81.2.145","article-title":"Adenoviral gene transfer of phospholamban in isolated rat cardiomyocytes. Rescue effects by concomitant gene transfer of sarcoplasmic reticulum Ca(2+)-ATPase","volume":"81","author":"Hajjar","year":"1997","journal-title":"Circ Res"},{"key":"10.1016\/j.cjca.2026.01.035_bib33","doi-asserted-by":"crossref","first-page":"5251","DOI":"10.1073\/pnas.95.9.5251","article-title":"Modulation of ventricular function through gene transfer in vivo","volume":"95","author":"Hajjar","year":"1998","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1016\/j.cjca.2026.01.035_bib34","doi-asserted-by":"crossref","first-page":"H1204","DOI":"10.1152\/ajpheart.00892.2006","article-title":"Transcoronary gene transfer of SERCA2a increases coronary blood flow and decreases cardiomyocyte size in a type 2 diabetic rat model","volume":"292","author":"Sakata","year":"2007","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"10.1016\/j.cjca.2026.01.035_bib35","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1161\/CIRCRESAHA.111.252981","article-title":"Gene therapy for heart failure","volume":"110","author":"Tilemann","year":"2012","journal-title":"Circ Res"},{"key":"10.1016\/j.cjca.2026.01.035_bib36","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1097\/FJC.0b013e3182a2e8b8","article-title":"Progress in gene therapy for heart failure","volume":"63","author":"Yerevanian","year":"2014","journal-title":"J Cardiovasc Pharmacol"},{"key":"10.1016\/j.cjca.2026.01.035_bib37","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1172\/JCI6026","article-title":"Enhancement of cardiac function after adenoviral-mediated in vivo intracoronary beta2-adrenergic receptor gene delivery","volume":"104","author":"Maurice","year":"1999","journal-title":"J Clin Invest"},{"key":"10.1016\/j.cjca.2026.01.035_bib38","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1161\/01.CIR.101.4.408","article-title":"Intracoronary adenovirus-mediated delivery and overexpression of the beta(2)-adrenergic receptor in the heart: prospects for molecular ventricular assistance","volume":"101","author":"Shah","year":"2000","journal-title":"Circulation"},{"key":"10.1016\/j.cjca.2026.01.035_bib39","doi-asserted-by":"crossref","first-page":"2308","DOI":"10.1161\/01.CIR.100.23.2308","article-title":"Restoration of contractile function in isolated cardiomyocytes from failing human hearts by gene transfer of SERCA2a","volume":"100","author":"del Monte","year":"1999","journal-title":"Circulation"},{"key":"10.1016\/j.cjca.2026.01.035_bib40","doi-asserted-by":"crossref","first-page":"5622","DOI":"10.1073\/pnas.0305778101","article-title":"Abrogation of ventricular arrhythmias in a model of ischemia and reperfusion by targeting myocardial calcium cycling","volume":"101","author":"del Monte","year":"2004","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1016\/j.cjca.2026.01.035_bib41","doi-asserted-by":"crossref","first-page":"1424","DOI":"10.1161\/hc3601.095574","article-title":"Improvement in survival and cardiac metabolism after gene transfer of sarcoplasmic reticulum Ca(2+)-ATPase in a rat model of heart failure","volume":"104","author":"del Monte","year":"2001","journal-title":"Circulation"},{"key":"10.1016\/j.cjca.2026.01.035_bib42","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1016\/j.jacc.2007.12.014","article-title":"Reversal of cardiac dysfunction after long-term expression of SERCA2a by gene transfer in a pre-clinical model of heart failure","volume":"51","author":"Kawase","year":"2008","journal-title":"J Am Coll Cardiol"},{"key":"10.1016\/j.cjca.2026.01.035_bib43","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1161\/CIRCEP.110.961615","article-title":"SERCA2a gene transfer decreases sarcoplasmic reticulum calcium leak and reduces ventricular arrhythmias in a model of chronic heart failure","volume":"4","author":"Lyon","year":"2011","journal-title":"Circ Arrhythm Electrophysiol"},{"key":"10.1016\/j.cjca.2026.01.035_bib44","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1161\/CIRCHEARTFAILURE.111.964692","article-title":"Plasticity of surface structures and beta(2)-adrenergic receptor localization in failing ventricular cardiomyocytes during recovery from heart failure","volume":"5","author":"Lyon","year":"2012","journal-title":"Circ Heart Fail"},{"key":"10.1016\/j.cjca.2026.01.035_bib45","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1073\/pnas.97.2.793","article-title":"Adenoviral gene transfer of SERCA2a improves left-ventricular function in aortic-banded rats in transition to heart failure","volume":"97","author":"Miyamoto","year":"2000","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1016\/j.cjca.2026.01.035_bib46","doi-asserted-by":"crossref","first-page":"2793","DOI":"10.1161\/01.CIR.91.11.2793","article-title":"Local delivery of vascular endothelial growth factor accelerates reendothelialization and attenuates intimal hyperplasia in balloon-injured rat carotid artery","volume":"91","author":"Asahara","year":"1995","journal-title":"Circulation"},{"key":"10.1016\/j.cjca.2026.01.035_bib47","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1161\/01.CIR.90.2.649","article-title":"Indirect angiogenic cytokines upregulate VEGF and bFGF gene expression in vascular smooth muscle cells, whereas hypoxia upregulates VEGF expression only","volume":"90","author":"Brogi","year":"1994","journal-title":"Circulation"},{"key":"10.1016\/j.cjca.2026.01.035_bib48","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1177\/1358863X9600100114","article-title":"Therapeutic angiogenesis: a new frontier for vascular therapy","volume":"1","author":"Isner","year":"1996","journal-title":"Vasc Med"},{"key":"10.1016\/j.cjca.2026.01.035_bib49","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1038\/8374","article-title":"Therapeutic angiogenesis for heart failure","volume":"5","author":"Isner","year":"1999","journal-title":"Nat Med"},{"key":"10.1016\/j.cjca.2026.01.035_bib50","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1016\/S0140-6736(96)03361-2","article-title":"Clinical evidence of angiogenesis after arterial gene transfer of phVEGF165 in patient with ischaemic limb","volume":"348","author":"Isner","year":"1996","journal-title":"Lancet"},{"key":"10.1016\/j.cjca.2026.01.035_bib51","doi-asserted-by":"crossref","first-page":"2800","DOI":"10.1161\/01.CIR.98.25.2800","article-title":"Gene therapy for myocardial angiogenesis: initial clinical results with direct myocardial injection of phVEGF165 as sole therapy for myocardial ischemia","volume":"98","author":"Losordo","year":"1998","journal-title":"Circulation"},{"key":"10.1016\/j.cjca.2026.01.035_bib52","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/74664","article-title":"Favorable effect of VEGF gene transfer on ischemic peripheral neuropathy","volume":"6","author":"Schratzberger","year":"2000","journal-title":"Nat Med"},{"key":"10.1016\/j.cjca.2026.01.035_bib53","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1172\/JCI117018","article-title":"Therapeutic angiogenesis. A single intraarterial bolus of vascular endothelial growth factor augments revascularization in a rabbit ischemic hind limb model","volume":"93","author":"Takeshita","year":"1994","journal-title":"J Clin Invest"},{"key":"10.1016\/j.cjca.2026.01.035_bib54","doi-asserted-by":"crossref","first-page":"3281","DOI":"10.1161\/01.CIR.94.12.3281","article-title":"Direct intramuscular gene transfer of naked DNA encoding vascular endothelial growth factor augments collateral development and tissue perfusion","volume":"94","author":"Tsurumi","year":"1996","journal-title":"Circulation"},{"key":"10.1016\/j.cjca.2026.01.035_bib55","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1161\/01.CIR.0000133324.38115.0A","article-title":"Local gene transfer of phVEGF-2 plasmid by gene-eluting stents: an alternative strategy for inhibition of restenosis","volume":"110","author":"Walter","year":"2004","journal-title":"Circulation"},{"key":"10.1016\/j.cjca.2026.01.035_bib56","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1161\/01.CIR.0000061911.47710.8A","article-title":"The VIVA trial: vascular endothelial growth factor in ischemia for vascular angiogenesis","volume":"107","author":"Henry","year":"2003","journal-title":"Circulation"},{"key":"10.1016\/j.cjca.2026.01.035_bib57","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1038\/mt.2009.70","article-title":"VEGF gene therapy fails to improve perfusion of ischemic myocardium in patients with advanced coronary disease: results of the NORTHERN trial","volume":"17","author":"Stewart","year":"2009","journal-title":"Mol Ther"},{"key":"10.1016\/j.cjca.2026.01.035_bib58","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1038\/gt.2009.4","article-title":"Eight-year safety follow-up of coronary artery disease patients after local intracoronary VEGF gene transfer","volume":"16","author":"Hedman","year":"2009","journal-title":"Gene Ther"},{"key":"10.1016\/j.cjca.2026.01.035_bib59","doi-asserted-by":"crossref","first-page":"2547","DOI":"10.1093\/eurheartj\/ehx352","article-title":"Adenoviral intramyocardial VEGF-D\u0394N\u0394C gene transfer increases myocardial perfusion reserve in refractory angina patients: a phase I\/IIa study with 1-year follow-up","volume":"38","author":"Hartikainen","year":"2017","journal-title":"Eur Heart J"},{"key":"10.1016\/j.cjca.2026.01.035_bib60","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1007\/s00270-001-0117-4","article-title":"Gene therapy techniques for peripheral arterial disease","volume":"25","author":"Manninen","year":"2002","journal-title":"Cardiovasc Intervent Radiol"},{"key":"10.1016\/j.cjca.2026.01.035_bib61","article-title":"Synthetic chemically modified mRNA (modRNA): toward a new technology platform for cardiovascular biology and medicine","volume":"5","author":"Chien","year":"2014","journal-title":"Cold Spring Harb Perspect Med"},{"key":"10.1016\/j.cjca.2026.01.035_bib62","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/j.scr.2014.06.007","article-title":"Cardiovascular regenerative therapeutics via synthetic paracrine factor modified mRNA","volume":"13","author":"Lui","year":"2014","journal-title":"Stem Cell Res"},{"key":"10.1016\/j.cjca.2026.01.035_bib63","doi-asserted-by":"crossref","first-page":"1172","DOI":"10.1038\/cr.2013.112","article-title":"Driving vascular endothelial cell fate of human multipotent Isl1+ heart progenitors with VEGF modified mRNA","volume":"23","author":"Lui","year":"2013","journal-title":"Cell Res"},{"key":"10.1016\/j.cjca.2026.01.035_bib64","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1038\/nbt.2682","article-title":"Modified mRNA directs the fate of heart progenitor cells and induces vascular regeneration after myocardial infarction","volume":"31","author":"Zangi","year":"2013","journal-title":"Nat Biotechnol"},{"key":"10.1016\/j.cjca.2026.01.035_bib65","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1161\/CIRCRESAHA.115.307935","article-title":"New insights into miR-17-92 cluster regulation and angiogenesis","volume":"118","author":"Fiedler","year":"2016","journal-title":"Circ Res"},{"issue":"suppl","key":"10.1016\/j.cjca.2026.01.035_bib66","first-page":"S135","article-title":"Sustained reduction of vein graft neointima formation by ex vivo TIMP-3 gene therapy","volume":"124","author":"George","year":"2011","journal-title":"Circulation"},{"key":"10.1016\/j.cjca.2026.01.035_bib67","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1002\/ijc.25404","article-title":"TIMP-3 promotes apoptosis in nonadherent small cell lung carcinoma cells lacking functional death receptor pathway","volume":"128","author":"Kallio","year":"2011","journal-title":"Int J Cancer"},{"key":"10.1016\/j.cjca.2026.01.035_bib68","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1186\/1749-8090-8-183","article-title":"Assessment of a novel, capsid-modified adenovirus with an improved vascular gene transfer profile","volume":"8","author":"White","year":"2013","journal-title":"J Cardiothorac Surg"},{"key":"10.1016\/j.cjca.2026.01.035_bib69","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1038\/nbt.1599","article-title":"Reengineering a receptor footprint of adeno-associated virus enables selective and systemic gene transfer to muscle","volume":"28","author":"Asokan","year":"2010","journal-title":"Nat Biotechnol"},{"key":"10.1016\/j.cjca.2026.01.035_bib70","doi-asserted-by":"crossref","first-page":"434","DOI":"10.2174\/15665232113136660007","article-title":"Biosafety of recombinant adeno-associated virus vectors","volume":"13","author":"Dismuke","year":"2013","journal-title":"Curr Gene Ther"},{"key":"10.1016\/j.cjca.2026.01.035_bib71","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1089\/hum.2015.025","article-title":"Adeno-associated virus at 50: a golden anniversary of discovery, research, and gene therapy success---a personal perspective","volume":"26","author":"Hastie","year":"2015","journal-title":"Hum Gene Ther"},{"key":"10.1016\/j.cjca.2026.01.035_bib72","article-title":"Rationally designed cardiotropic AAV capsid demonstrates 30 fold higher efficiency in human vs porcine heart","volume":"30","author":"Tretiakova","year":"2022","journal-title":"Mol Ther"},{"key":"10.1016\/j.cjca.2026.01.035_bib73","doi-asserted-by":"crossref","first-page":"835","DOI":"10.4155\/tde.12.63","article-title":"Recombinant adeno-associated virus: clinical application and development as a gene-therapy vector","volume":"3","author":"Xiao","year":"2012","journal-title":"Ther Deliv"},{"key":"10.1016\/j.cjca.2026.01.035_bib74","doi-asserted-by":"crossref","DOI":"10.1038\/mtm.2014.67","article-title":"Effectiveness of gene delivery systems for pluripotent and differentiated cells","volume":"2","author":"Rapti","year":"2015","journal-title":"Mol Ther Methods Clin Dev"},{"key":"10.1016\/j.cjca.2026.01.035_bib75","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1089\/hum.2024.156","article-title":"Thrombotic microangiopathy associated with systemic adeno-associated virus gene transfer: review of reported cases","volume":"36","author":"Laforet","year":"2025","journal-title":"Hum Gene Ther"},{"key":"10.1016\/j.cjca.2026.01.035_bib76","doi-asserted-by":"crossref","DOI":"10.1172\/JCI173510","article-title":"Thrombotic microangiopathy following systemic AAV administration is dependent on anti-capsid antibodies","volume":"134","author":"Salabarria","year":"2024","journal-title":"J Clin Invest"},{"key":"10.1016\/j.cjca.2026.01.035_bib77","doi-asserted-by":"crossref","DOI":"10.1161\/CIRCEP.120.008420","article-title":"Stabilizer cell gene therapy: a less-is-more strategy to prevent cardiac arrhythmias","volume":"13","author":"Liu","year":"2020","journal-title":"Circ Arrhythm Electrophysiol"},{"key":"10.1016\/j.cjca.2026.01.035_bib78","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1161\/CIRCRESAHA.116.309396","article-title":"Dilated cardiomyopathy: genetic determinants and mechanisms","volume":"121","author":"McNally","year":"2017","journal-title":"Circ Res"},{"key":"10.1016\/j.cjca.2026.01.035_bib79","doi-asserted-by":"crossref","first-page":"2119","DOI":"10.1001\/jama.2015.3595","article-title":"The precision medicine initiative: a new national effort","volume":"313","author":"Ashley","year":"2015","journal-title":"JAMA"},{"key":"10.1016\/j.cjca.2026.01.035_bib80","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1161\/01.CIR.92.4.778","article-title":"Alterations of sarcoplasmic reticulum proteins in failing human dilated cardiomyopathy","volume":"92","author":"Meyer","year":"1995","journal-title":"Circulation"},{"key":"10.1016\/j.cjca.2026.01.035_bib81","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1161\/CIRCULATIONAHA.123.064513","article-title":"SERCA2a protein levels are unaltered in human heart failure","volume":"148","author":"Ragone","year":"2023","journal-title":"Circulation"},{"key":"10.1016\/j.cjca.2026.01.035_bib82","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1007\/s00424-003-1163-3","article-title":"Ser16-, but not Thr17-phosphorylation of phospholamban influences frequency-dependent force generation in human myocardium","volume":"447","author":"Brixius","year":"2003","journal-title":"Pflugers Arch"},{"key":"10.1016\/j.cjca.2026.01.035_bib83","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1016\/j.jacc.2004.05.049","article-title":"Altered myocardial Ca2+ cycling after left ventricular assist device support in the failing human heart","volume":"44","author":"Chaudhary","year":"2004","journal-title":"J Am Coll Cardiol"},{"key":"10.1016\/j.cjca.2026.01.035_bib84","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1042\/BJ20051427","article-title":"Ca2+-ATPases in non-failing and failing heart: evidence for a novel cardiac sarco\/endoplasmic reticulum Ca2+-ATPase 2 isoform (SERCA2c)","volume":"395","author":"Dally","year":"2006","journal-title":"Biochem J"},{"issue":"suppl 1","key":"10.1016\/j.cjca.2026.01.035_bib85","first-page":"I72","article-title":"Modulation of SERCA: implications for the failing human heart","volume":"97","author":"Frank","year":"2002","journal-title":"Basic Res Cardiol"},{"key":"10.1016\/j.cjca.2026.01.035_bib86","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1006\/jmcc.2001.1366","article-title":"SERCA pump level is a critical determinant of Ca(2+)homeostasis and cardiac contractility","volume":"33","author":"Periasamy","year":"2001","journal-title":"J Mol Cell Cardiol"},{"issue":"suppl 1","key":"10.1016\/j.cjca.2026.01.035_bib87","first-page":"I63","article-title":"Sarcoplasmic reticulum Ca2+ load in human heart failure","volume":"97","author":"Pieske","year":"2002","journal-title":"Basic Res Cardiol"},{"issue":"suppl 4S","key":"10.1016\/j.cjca.2026.01.035_bib88","first-page":"1","article-title":"A phase 1 clinical trial of high dose AAV1.SERCA2a in patients with heart failure: Modulation of SERCA2a of Intra-myocytic Calcium Trafficking in Heart Failure With Reduced Ejection Fraction (MUSIC-HFrEF)","volume":"32","author":"Jaski","year":"2024","journal-title":"Mol Ther"},{"key":"10.1016\/j.cjca.2026.01.035_bib89","doi-asserted-by":"crossref","first-page":"2038","DOI":"10.1038\/mt.2014.127","article-title":"Cardiac I-1c overexpression with reengineered AAV improves cardiac function in swine ischemic heart failure","volume":"22","author":"Ishikawa","year":"2014","journal-title":"Mol Ther"},{"key":"10.1016\/j.cjca.2026.01.035_bib90","doi-asserted-by":"crossref","first-page":"1744","DOI":"10.1016\/j.jacc.2017.08.013","article-title":"Protein phosphatase inhibitor-1 gene therapy in a swine model of nonischemic heart failure","volume":"70","author":"Watanabe","year":"2017","journal-title":"J Am Coll Cardiol"},{"key":"10.1016\/j.cjca.2026.01.035_bib91","doi-asserted-by":"crossref","first-page":"3845","DOI":"10.1038\/s41591-025-04011-z","article-title":"Cardiotropic AAV gene therapy for heart failure: a phase 1 trial","volume":"31","author":"Henry","year":"2025","journal-title":"Nat Med"},{"key":"10.1016\/j.cjca.2026.01.035_bib92","first-page":"0","article-title":"Targeting the hippo pathway for cardiac regeneration","volume":"40","author":"Li","year":"2025","journal-title":"Physiology (Bethesda)"},{"key":"10.1016\/j.cjca.2026.01.035_bib93","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.stem.2022.12.004","article-title":"Regrowing the heart, one TREE at a time","volume":"30","author":"Steimle","year":"2023","journal-title":"Cell Stem Cell"},{"key":"10.1016\/j.cjca.2026.01.035_bib94","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1038\/s41569-018-0063-3","article-title":"The Hippo pathway in the heart: pivotal roles in development, disease, and regeneration","volume":"15","author":"Wang","year":"2018","journal-title":"Nat Rev Cardiol"},{"key":"10.1016\/j.cjca.2026.01.035_bib95","doi-asserted-by":"crossref","first-page":"972","DOI":"10.1056\/NEJMoa2412392","article-title":"Phase 1 study of AAV9.LAMP2B gene therapy in Danon disease","volume":"392","author":"Greenberg","year":"2025","journal-title":"N Engl J Med"},{"key":"10.1016\/j.cjca.2026.01.035_bib96","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.yjmcc.2014.11.018","article-title":"Haploinsufficiency of MYBPC3 exacerbates the development of hypertrophic cardiomyopathy in heterozygous mice","volume":"79","author":"Barefield","year":"2015","journal-title":"J Mol Cell Cardiol"},{"key":"10.1016\/j.cjca.2026.01.035_bib97","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1007\/s00424-013-1409-7","article-title":"MYBPC3 in hypertrophic cardiomyopathy: from mutation identification to RNA-based correction","volume":"466","author":"Behrens-Gawlik","year":"2014","journal-title":"Pflugers Arch"},{"key":"10.1016\/j.cjca.2026.01.035_bib98","doi-asserted-by":"crossref","first-page":"1635","DOI":"10.1093\/cvr\/cvaa107","article-title":"Gene therapy for inherited arrhythmias","volume":"116","author":"Bezzerides","year":"2020","journal-title":"Cardiovasc Res"},{"key":"10.1016\/j.cjca.2026.01.035_bib99","doi-asserted-by":"crossref","first-page":"5515","DOI":"10.1038\/ncomms6515","article-title":"Mybpc3 gene therapy for neonatal cardiomyopathy enables long-term disease prevention in mice","volume":"5","author":"Mearini","year":"2014","journal-title":"Nat Commun"},{"key":"10.1016\/j.cjca.2026.01.035_bib100","doi-asserted-by":"crossref","first-page":"2628","DOI":"10.1093\/cvr\/cvaf200","article-title":"First-in-human study of TN-201, an AAV9 gene replacement therapy in MYBPC3-associated hypertrophic cardiomyopathy: initial safety, pharmacodynamic, and imaging results from MyPEAK-1","volume":"121","author":"Desai","year":"2025","journal-title":"Cardiovasc Res"},{"key":"10.1016\/j.cjca.2026.01.035_bib101","doi-asserted-by":"crossref","first-page":"6324","DOI":"10.1038\/s41467-021-26623-y","article-title":"Gain-of-function cardiomyopathic mutations in RBM20 rewire splicing regulation and re-distribute ribonucleoprotein granules within processing bodies","volume":"12","author":"Fenix","year":"2021","journal-title":"Nat Commun"},{"key":"10.1016\/j.cjca.2026.01.035_bib102","doi-asserted-by":"crossref","first-page":"4101","DOI":"10.3390\/jcm10184101","article-title":"RBM20-related cardiomyopathy: current understanding and future options","volume":"10","author":"Koelemen","year":"2021","journal-title":"J Clin Med"},{"key":"10.1016\/j.cjca.2026.01.035_bib103","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.ade1633","article-title":"Precise genomic editing of pathogenic mutations in RBM20 rescues dilated cardiomyopathy","volume":"14","author":"Nishiyama","year":"2022","journal-title":"Sci Transl Med"},{"key":"10.1016\/j.cjca.2026.01.035_bib104","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.abe8952","article-title":"Therapeutic inhibition of RBM20 improves diastolic function in a murine heart failure model and human engineered heart tissue","volume":"13","author":"Radke","year":"2021","journal-title":"Sci Transl Med"},{"key":"10.1016\/j.cjca.2026.01.035_bib105","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1093\/eurheartj\/ehaf667","article-title":"Transthyretin amyloid cardiomyopathy: from cause to novel treatments","volume":"47","author":"Fontana","year":"2026","journal-title":"Eur Heart J"},{"key":"10.1016\/j.cjca.2026.01.035_bib106","first-page":"1174","article-title":"Novel strategy for AAV vector design in gene therapy and its biosafety assessment","volume":"38","author":"Gao","year":"2025","journal-title":"Pak J Pharm Sci"},{"key":"10.1016\/j.cjca.2026.01.035_bib107","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1007\/978-1-0716-3961-0_15","article-title":"Recombinant AAV purification","volume":"2829","author":"Joshi","year":"2024","journal-title":"Methods Mol Biol"},{"key":"10.1016\/j.cjca.2026.01.035_bib108","doi-asserted-by":"crossref","DOI":"10.1016\/j.omtm.2025.101551","article-title":"Innate immune response to AAV-based gene therapy vectors: mechanisms of complement activation and cytokine release","volume":"33","author":"Xicluna","year":"2025","journal-title":"Mol Ther Methods Clin Dev"},{"key":"10.1016\/j.cjca.2026.01.035_bib109","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1161\/CIRCRESAHA.125.326716","article-title":"CAR macrophages engineered in vivo for attenuating myocardial ischemia-reperfusion injury","volume":"137","author":"Du","year":"2025","journal-title":"Circ Res"},{"key":"10.1016\/j.cjca.2026.01.035_bib110","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1161\/CIRCULATIONAHA.124.071217","article-title":"Human single-nucleus RNA sequencing identifies CD47 as a therapeutic target for doxorubicin-induced cardiomyopathy","volume":"152","author":"Guo","year":"2025","journal-title":"Circulation"},{"key":"10.1016\/j.cjca.2026.01.035_bib111","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1038\/s41551-025-01511-8","article-title":"Targeting and tracking mRNA lipid nanoparticles at the particle, transcript and protein level","volume":"9","author":"Kang","year":"2025","journal-title":"Nat Biomed Eng"},{"key":"10.1016\/j.cjca.2026.01.035_bib112","doi-asserted-by":"crossref","DOI":"10.1038\/s41551-025-01523-4","article-title":"A microphysiological system for screening lipid nanoparticle-mRNA complexes predicts in vivo heart transfection efficacy","author":"Neiman","year":"2025","journal-title":"Nat Biomed Eng"},{"key":"10.1016\/j.cjca.2026.01.035_bib113","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1038\/s41565-025-01974-5","article-title":"Limiting endosomal damage sensing reduces inflammation triggered by lipid nanoparticle endosomal escape","volume":"20","author":"Omo-Lamai","year":"2025","journal-title":"Nat Nanotechnol"},{"key":"10.1016\/j.cjca.2026.01.035_bib114","doi-asserted-by":"crossref","DOI":"10.1016\/j.jconrel.2025.114382","article-title":"Circular RNA-based therapy provides sustained and robust expression of FGF2 to accelerate diabetic wound healing","volume":"388","author":"Yao","year":"2025","journal-title":"J Control Release"},{"key":"10.1016\/j.cjca.2026.01.035_bib115","doi-asserted-by":"crossref","first-page":"2336","DOI":"10.1016\/j.ymthe.2025.04.040","article-title":"Patient-centered long-term follow-up for gene therapies aligns with ethics and science","volume":"33","author":"Chapman","year":"2025","journal-title":"Mol Ther"},{"key":"10.1016\/j.cjca.2026.01.035_bib116","doi-asserted-by":"crossref","DOI":"10.1212\/WNL.0000000000214085","article-title":"Microdystrophin gene therapy for Duchenne muscular dystrophy: the ethics and financial toxicity of exuberant hope","volume":"105","author":"Smith","year":"2025","journal-title":"Neurology"}],"container-title":["Canadian Journal of Cardiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0828282X26000644?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0828282X26000644?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T01:11:33Z","timestamp":1778202693000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0828282X26000644"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5]]},"references-count":116,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,5]]}},"alternative-id":["S0828282X26000644"],"URL":"https:\/\/doi.org\/10.1016\/j.cjca.2026.01.035","relation":{},"ISSN":["0828-282X"],"issn-type":[{"value":"0828-282X","type":"print"}],"subject":[],"published":{"date-parts":[[2026,5]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"The Past, Present, and Future of Cardiac Gene Therapy","name":"articletitle","label":"Article Title"},{"value":"Canadian Journal of Cardiology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.cjca.2026.01.035","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The Authors. Published by Elsevier Inc. on behalf of the Canadian Cardiovascular Society.","name":"copyright","label":"Copyright"}]}}