{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T04:15:40Z","timestamp":1791346540130,"version":"4.3.1"},"reference-count":93,"publisher":"Elsevier BV","issue":"6","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T00:00:00Z","timestamp":1771200000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000968","name":"American Heart Association Inc","doi-asserted-by":"publisher","award":["959536"],"award-info":[{"award-number":["959536"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association Inc","doi-asserted-by":"publisher","award":["917025"],"award-info":[{"award-number":["917025"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016867","name":"ZOLL Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016867","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008237","name":"Department of Surgery","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008237","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R15HL168688"],"award-info":[{"award-number":["R15HL168688"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01HL166280"],"award-info":[{"award-number":["R01HL166280"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01HL147921"],"award-info":[{"award-number":["R01HL147921"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R35GM143532"],"award-info":[{"award-number":["R35GM143532"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01HL163258"],"award-info":[{"award-number":["R01HL163258"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01HL174616"],"award-info":[{"award-number":["R01HL174616"]}],"id":[{"id":"10.13039\/100000002","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":[[2026,6]]},"DOI":"10.1016\/j.ymthe.2026.02.027","type":"journal-article","created":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T15:10:47Z","timestamp":1773069047000},"page":"3320-3333","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":3,"title":["CRISPR-Cas-based activation of PPARGC1A boosts endogenous mitochondria and enhances cardiac function after myocardial infarction"],"prefix":"10.1016","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2262-7800","authenticated-orcid":false,"given":"Mario","family":"Escobar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saad A.","family":"Malik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mira A.","family":"Srinivasa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel A.","family":"Mendez-Sosa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica M.","family":"Miller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha L.","family":"Lydon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandy N.","family":"Luong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pretty R.","family":"Mathew","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riham R.E.","family":"Abouleisa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suridh","family":"Chakravarty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saliha","family":"Pathan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamer M.A.","family":"Mohamed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravi K.","family":"Ghanta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3064-8532","authenticated-orcid":false,"given":"Isaac B.","family":"Hilton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ymthe.2026.02.027_bib1","doi-asserted-by":"crossref","first-page":"e56","DOI":"10.1161\/CIR.0000000000000659","article-title":"Heart Disease and Stroke Statistics\u20142019 Update: A Report From the American Heart Association","volume":"139","author":"Benjamin","year":"2019","journal-title":"Circulation"},{"key":"10.1016\/j.ymthe.2026.02.027_bib2","doi-asserted-by":"crossref","first-page":"2057","DOI":"10.1161\/CIRCULATIONAHA.108.784215","article-title":"Long-term trends in the incidence of heart failure after myocardial infarction","volume":"118","author":"Velagaleti","year":"2008","journal-title":"Circulation"},{"key":"10.1016\/j.ymthe.2026.02.027_bib3","doi-asserted-by":"crossref","first-page":"ii13","DOI":"10.1093\/europace\/eur081","article-title":"What are the costs of heart failure?","volume":"13","author":"Braunschweig","year":"2011","journal-title":"Europace."},{"key":"10.1016\/j.ymthe.2026.02.027_bib4","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1161\/HHF.0b013e318291329a","article-title":"Forecasting the impact of heart failure in the United States: a policy statement from the American Heart Association","volume":"6","author":"Heidenreich","year":"2013","journal-title":"Circ. Heart Fail."},{"key":"10.1016\/j.ymthe.2026.02.027_bib5","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.1161\/CIRCRESAHA.121.318241","article-title":"Cardiac Energy Metabolism in Heart Failure","volume":"128","author":"Lopaschuk","year":"2021","journal-title":"Circ. Res."},{"key":"10.1016\/j.ymthe.2026.02.027_bib6","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1161\/CIRCULATIONAHA.119.040551","article-title":"Unlocking the Secrets of Mitochondria in the Cardiovascular System: Path to a Cure in Heart Failure\u2014A Report from the 2018 National Heart, Lung, and Blood Institute Workshop","volume":"140","author":"Tian","year":"2019","journal-title":"Circulation"},{"key":"10.1016\/j.ymthe.2026.02.027_bib7","doi-asserted-by":"crossref","first-page":"3716","DOI":"10.1172\/JCI120849","article-title":"Mitochondrial dysfunction in pathophysiology of heart failure","volume":"128","author":"Zhou","year":"2018","journal-title":"J. Clin. Invest."},{"key":"10.1016\/j.ymthe.2026.02.027_bib8","doi-asserted-by":"crossref","first-page":"90","DOI":"10.12703\/P6-90","article-title":"Rethinking cardiac metabolism: metabolic cycles to refuel and rebuild the failing heart","volume":"6","author":"Taegtmeyer","year":"2014","journal-title":"F1000Prime Rep."},{"key":"10.1016\/j.ymthe.2026.02.027_bib9","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1093\/cvr\/cvn184","article-title":"Cardiac mitochondria in heart failure: decrease in respirasomes and oxidative phosphorylation","volume":"80","author":"Rosca","year":"2008","journal-title":"Cardiovasc. Res."},{"key":"10.1016\/j.ymthe.2026.02.027_bib10","doi-asserted-by":"crossref","first-page":"1140","DOI":"10.1056\/NEJMra063052","article-title":"The failing heart--an engine out of fuel","volume":"356","author":"Neubauer","year":"2007","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.ymthe.2026.02.027_bib11","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1152\/physrev.00015.2009","article-title":"Myocardial fatty acid metabolism in health and disease","volume":"90","author":"Lopaschuk","year":"2010","journal-title":"Physiol. Rev."},{"key":"10.1016\/j.ymthe.2026.02.027_bib12","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1038\/s41569-023-00887-x","article-title":"Metabolic mechanisms in physiological and pathological cardiac hypertrophy: new paradigms and challenges","volume":"20","author":"Ritterhoff","year":"2023","journal-title":"Nat. Rev. Cardiol."},{"key":"10.1016\/j.ymthe.2026.02.027_bib13","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.aac7410","article-title":"Novel targets for mitochondrial medicine","volume":"8","author":"Wang","year":"2016","journal-title":"Sci. Transl. Med."},{"key":"10.1016\/j.ymthe.2026.02.027_bib14","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1038\/nrcardio.2016.203","article-title":"Expert consensus document: Mitochondrial function as a therapeutic target in heart failure","volume":"14","author":"Brown","year":"2017","journal-title":"Nat. Rev. Cardiol."},{"key":"10.1016\/j.ymthe.2026.02.027_bib15","doi-asserted-by":"crossref","first-page":"1960","DOI":"10.1161\/RES.0000000000000104","article-title":"Mitochondrial Function, Biology, and Role in Disease: A Scientific Statement From the American Heart Association","volume":"118","author":"Murphy","year":"2016","journal-title":"Circ. Res."},{"key":"10.1016\/j.ymthe.2026.02.027_bib16","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1016\/j.jtcvs.2016.10.077","article-title":"Myocardial rescue with autologous mitochondrial transplantation in a porcine model of ischemia\/reperfusion","volume":"153","author":"Kaza","year":"2017","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"10.1016\/j.ymthe.2026.02.027_bib17","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1016\/j.jtcvs.2020.10.151","article-title":"Autologous mitochondrial transplantation for cardiogenic shock in pediatric patients following ischemia-reperfusion injury","volume":"162","author":"Guariento","year":"2021","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"10.1016\/j.ymthe.2026.02.027_bib18","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1016\/j.jacbts.2019.08.007","article-title":"A Novel Biological Strategy for Myocardial Protection by Intracoronary Delivery of Mitochondria: Safety and Efficacy","volume":"4","author":"Shin","year":"2019","journal-title":"JACC. Basic Transl. Sci."},{"key":"10.1016\/j.ymthe.2026.02.027_bib19","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1093\/ejcts\/ezz326","article-title":"Mitochondrial transplantation for myocardial protection in diabetic hearts","volume":"57","author":"Doulamis","year":"2020","journal-title":"Eur. J. Cardiothorac. Surg."},{"key":"10.1016\/j.ymthe.2026.02.027_bib20","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0160889","article-title":"Intracoronary Delivery of Mitochondria to the Ischemic Heart for Cardioprotection","volume":"11","author":"Cowan","year":"2016","journal-title":"PLoS One"},{"key":"10.1016\/j.ymthe.2026.02.027_bib21","doi-asserted-by":"crossref","first-page":"H966","DOI":"10.1152\/ajpheart.00883.2012","article-title":"Transplantation of autologously derived mitochondria protects the heart from ischemia-reperfusion injury","volume":"304","author":"Masuzawa","year":"2013","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"10.1016\/j.ymthe.2026.02.027_bib22","doi-asserted-by":"crossref","first-page":"H94","DOI":"10.1152\/ajpheart.00567.2008","article-title":"Injection of isolated mitochondria during early reperfusion for cardioprotection","volume":"296","author":"McCully","year":"2009","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"10.1016\/j.ymthe.2026.02.027_bib23","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.jacbts.2018.12.005","article-title":"Elamipretide Improves Mitochondrial Function in the Failing Human Heart","volume":"4","author":"Chatfield","year":"2019","journal-title":"JACC. Basic Transl. Sci."},{"key":"10.1016\/j.ymthe.2026.02.027_bib24","doi-asserted-by":"crossref","DOI":"10.1161\/CIRCHEARTFAILURE.117.004389","article-title":"Novel Mitochondria-Targeting Peptide in Heart Failure Treatment: A Randomized, Placebo-Controlled Trial of Elamipretide","volume":"10","author":"Daubert","year":"2017","journal-title":"Circ. Heart Fail."},{"key":"10.1016\/j.ymthe.2026.02.027_bib25","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1177\/1074248413508003","article-title":"Reduction of Early Reperfusion Injury With the Mitochondria-Targeting Peptide Bendavia","volume":"19","author":"Brown","year":"2014","journal-title":"J. Cardiovasc. Pharmacol. Ther."},{"key":"10.1016\/j.ymthe.2026.02.027_bib26","doi-asserted-by":"crossref","DOI":"10.1161\/CIRCHEARTFAILURE.115.002206","article-title":"Chronic Therapy With Elamipretide (MTP-131), a Novel Mitochondria-Targeting Peptide, Improves Left Ventricular and Mitochondrial Function in Dogs With Advanced Heart Failure","volume":"9","author":"Sabbah","year":"2016","journal-title":"Circ. Heart Fail."},{"key":"10.1016\/j.ymthe.2026.02.027_bib27","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1002\/ar.1090600408","article-title":"Studies on cell structure by the freezing-drying method VI. The preparation and properties of mitochondria","volume":"60","author":"Bensley","year":"1934","journal-title":"Anat. Rec. (Hoboken)."},{"key":"10.1016\/j.ymthe.2026.02.027_bib28","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1111\/j.1471-4159.1990.tb04189.x","article-title":"Rapid Isolation of Metabolically Active Mitochondria from Rat Brain and Subregions Using Percoll Density Gradient Centrifugation","volume":"55","author":"Sims","year":"1990","journal-title":"J. Neurochem."},{"key":"10.1016\/j.ymthe.2026.02.027_bib29","doi-asserted-by":"crossref","first-page":"9656","DOI":"10.1038\/s41598-019-45568-3","article-title":"Fractionated mitochondrial magnetic separation for isolation of synaptic mitochondria from brain tissue","volume":"9","author":"Hubbard","year":"2019","journal-title":"Sci. Rep."},{"key":"10.1016\/j.ymthe.2026.02.027_bib30","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.mito.2017.03.004","article-title":"Mitochondrial transplantation: From animal models to clinical use in humans","volume":"34","author":"McCully","year":"2017","journal-title":"Mitochondrion"},{"key":"10.1016\/j.ymthe.2026.02.027_bib31","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/S0092-8674(00)80611-X","article-title":"Mechanisms Controlling Mitochondrial Biogenesis and Respiration through the Thermogenic Coactivator PGC-1","volume":"98","author":"Wu","year":"1999","journal-title":"Cell"},{"key":"10.1016\/j.ymthe.2026.02.027_bib32","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1016\/S0092-8674(00)81410-5","article-title":"A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis","volume":"92","author":"Puigserver","year":"1998","journal-title":"Cell"},{"key":"10.1016\/j.ymthe.2026.02.027_bib33","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/j.cmet.2005.05.004","article-title":"Metabolic control through the PGC-1 family of transcription coactivators","volume":"1","author":"Lin","year":"2005","journal-title":"Cell Metab."},{"key":"10.1016\/j.ymthe.2026.02.027_bib34","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1172\/JCI27794","article-title":"PGC-1 coactivators: inducible regulators of energy metabolism in health and disease","volume":"116","author":"Finck","year":"2006","journal-title":"J. Clin. Invest."},{"key":"10.1016\/j.ymthe.2026.02.027_bib35","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1172\/JCI10268","article-title":"Peroxisome proliferator\u2013activated receptor \u03b3 coactivator-1 promotes cardiac mitochondrial biogenesis","volume":"106","author":"Lehman","year":"2000","journal-title":"J. Clin. Invest."},{"key":"10.1016\/j.ymthe.2026.02.027_bib36","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1161\/01.RES.0000117088.36577.EB","article-title":"Cardiac-Specific Induction of the Transcriptional Coactivator Peroxisome Proliferator-Activated Receptor \u03b3 Coactivator-1\u03b1 Promotes Mitochondrial Biogenesis and Reversible Cardiomyopathy in a Developmental Stage-Dependent Manner","volume":"94","author":"Russell","year":"2004","journal-title":"Circ. Res."},{"key":"10.1016\/j.ymthe.2026.02.027_bib37","doi-asserted-by":"crossref","first-page":"1861","DOI":"10.1093\/hmg\/ddr618","article-title":"Sustained expression of PGC-1\u03b1 in the rat nigrostriatal system selectively impairs dopaminergic function","volume":"21","author":"Ciron","year":"2012","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.ymthe.2026.02.027_bib38","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1161\/CIRCRESAHA.119.315529","article-title":"Fine-Tuning of PGC1\u03b1 Expression Regulates Cardiac Function and Longevity","volume":"125","author":"Zhu","year":"2019","journal-title":"Circ. Res."},{"key":"10.1016\/j.ymthe.2026.02.027_bib39","doi-asserted-by":"crossref","DOI":"10.26508\/lsa.202101034","article-title":"High levels of TFAM repress mammalian mitochondrial DNA transcription in vivo","volume":"4","author":"Bonekamp","year":"2021","journal-title":"Life Sci. Alliance"},{"key":"10.1016\/j.ymthe.2026.02.027_bib40","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1016\/j.stem.2016.07.001","article-title":"Targeted Epigenetic Remodeling of Endogenous Loci by CRISPR\/Cas9-Based Transcriptional Activators Directly Converts Fibroblasts to Neuronal Cells","volume":"19","author":"Black","year":"2016","journal-title":"Cell Stem Cell"},{"key":"10.1016\/j.ymthe.2026.02.027_bib41","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1038\/s41467-021-21188-2","article-title":"Programmable human histone phosphorylation and gene activation using a CRISPR\/Cas9-based chromatin kinase","volume":"12","author":"Li","year":"2021","journal-title":"Nat. Commun."},{"key":"10.1016\/j.ymthe.2026.02.027_bib42","doi-asserted-by":"crossref","first-page":"1716","DOI":"10.1038\/s41592-023-02036-1","article-title":"Compact engineered human mechanosensitive transactivation modules enable potent and versatile synthetic transcriptional control","volume":"20","author":"Mahata","year":"2023","journal-title":"Nat. Methods"},{"key":"10.1016\/j.ymthe.2026.02.027_bib43","doi-asserted-by":"crossref","first-page":"3239","DOI":"10.1021\/acssynbio.2c00156","article-title":"Quantification of Genome Editing and Transcriptional Control Capabilities Reveals Hierarchies among Diverse CRISPR\/Cas Systems in Human Cells","volume":"11","author":"Escobar","year":"2022","journal-title":"ACS Synth. Biol."},{"key":"10.1016\/j.ymthe.2026.02.027_bib44","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1038\/nbt.3199","article-title":"Epigenome editing by a CRISPR-Cas9-based acetyltransferase activates genes from promoters and enhancers","volume":"33","author":"Hilton","year":"2015","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.ymthe.2026.02.027_bib45","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1038\/nmeth.3312","article-title":"Highly efficient Cas9-mediated transcriptional programming","volume":"12","author":"Chavez","year":"2015","journal-title":"Nat. Methods"},{"key":"10.1016\/j.ymthe.2026.02.027_bib46","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1016\/j.cell.2013.02.022","article-title":"Repurposing CRISPR as an RNA-Guided Platform for Sequence-Specific Control of Gene Expression","volume":"152","author":"Qi","year":"2013","journal-title":"Cell"},{"key":"10.1016\/j.ymthe.2026.02.027_bib47","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1016\/j.cell.2013.06.044","article-title":"CRISPR-Mediated Modular RNA-Guided Regulation of Transcription in Eukaryotes","volume":"154","author":"Gilbert","year":"2013","journal-title":"Cell"},{"key":"10.1016\/j.ymthe.2026.02.027_bib48","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gku749","article-title":"Multiplex CRISPR\/Cas9-based genome engineering from a single lentiviral vector","volume":"42","author":"Kabadi","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.ymthe.2026.02.027_bib49","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1038\/nmeth.2600","article-title":"RNA-guided gene activation by CRISPR-Cas9\u2013based transcription factors","volume":"10","author":"Perez-Pinera","year":"2013","journal-title":"Nat. Methods"},{"key":"10.1016\/j.ymthe.2026.02.027_bib50","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1038\/s41573-022-00476-6","article-title":"Engineering the next generation of cell-based therapeutics","volume":"21","author":"Bashor","year":"2022","journal-title":"Nat. Rev. Drug Discov."},{"key":"10.1016\/j.ymthe.2026.02.027_bib51","doi-asserted-by":"crossref","first-page":"57","DOI":"10.3390\/dna5040057","article-title":"CRISPR-Based Transcriptional Regulation: Technologies, Applications, and Future Directions","volume":"5","author":"Srinivasa","year":"2025","journal-title":"DNA"},{"key":"10.1016\/j.ymthe.2026.02.027_bib52","doi-asserted-by":"crossref","DOI":"10.1016\/j.nbd.2020.104954","article-title":"CRISPR\/dCas9-based Scn1a gene activation in inhibitory neurons ameliorates epileptic and behavioral phenotypes of Dravet syndrome model mice","volume":"141","author":"Yamagata","year":"2020","journal-title":"Neurobiol. Dis."},{"key":"10.1016\/j.ymthe.2026.02.027_bib53","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.ymthe.2019.08.018","article-title":"dCas9-Based Scn1a Gene Activation Restores Inhibitory Interneuron Excitability and Attenuates Seizures in Dravet Syndrome Mice","volume":"28","author":"Colasante","year":"2020","journal-title":"Mol. Ther."},{"key":"10.1016\/j.ymthe.2026.02.027_bib54","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1038\/nbt.3081","article-title":"Cationic lipid-mediated delivery of proteins enables efficient protein-based genome editing in vitro and in vivo","volume":"33","author":"Zuris","year":"2015","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.ymthe.2026.02.027_bib55","doi-asserted-by":"crossref","first-page":"5660","DOI":"10.1021\/acsnano.1c10631","article-title":"Robust, Durable Gene Activation In Vivo via mRNA-Encoded Activators","volume":"16","author":"Beyersdorf","year":"2022","journal-title":"ACS Nano"},{"key":"10.1016\/j.ymthe.2026.02.027_bib56","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.aba5614","article-title":"A gene therapy for inherited blindness using dCas9-VPR-mediated transcriptional activation","volume":"6","author":"B\u00f6hm","year":"2020","journal-title":"Sci. Adv."},{"key":"10.1016\/j.ymthe.2026.02.027_bib57","article-title":"CRISPRa-induced upregulation of human LAMA1 compensates for LAMA2-deficiency in Merosin-deficient congenital muscular dystrophy","author":"Arockiaraj","year":"2023","journal-title":"bioRxiv."},{"key":"10.1016\/j.ymthe.2026.02.027_bib58","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1038\/nature14299","article-title":"In vivo genome editing using Staphylococcus aureus Cas9","volume":"520","author":"Ran","year":"2015","journal-title":"Nature"},{"key":"10.1016\/j.ymthe.2026.02.027_bib59","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1016\/j.cell.2015.09.038","article-title":"Cpf1 Is a Single RNA-Guided Endonuclease of a Class 2 CRISPR-Cas System","volume":"163","author":"Zetsche","year":"2015","journal-title":"Cell"},{"key":"10.1016\/j.ymthe.2026.02.027_bib60","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1038\/s41587-018-0011-0","article-title":"Engineered CRISPR-Cas12a variants with increased activities and improved targeting ranges for gene, epigenetic and base editing","volume":"37","author":"Kleinstiver","year":"2019","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.ymthe.2026.02.027_bib61","doi-asserted-by":"crossref","first-page":"7842","DOI":"10.1093\/nar\/gkac582","article-title":"Systematic comparison of CRISPR-based transcriptional activators uncovers gene-regulatory features of enhancer-promoter interactions","volume":"50","author":"Wang","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.ymthe.2026.02.027_bib62","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1038\/nmeth.3871","article-title":"Comparison of Cas9 activators in multiple species","volume":"13","author":"Chavez","year":"2016","journal-title":"Nat. Methods"},{"key":"10.1016\/j.ymthe.2026.02.027_bib63","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1007\/978-1-4939-1875-1_3","article-title":"PCR based determination of mitochondrial DNA copy number in multiple species","volume":"1241","author":"Rooney","year":"2015","journal-title":"Methods Mol. Biol."},{"key":"10.1016\/j.ymthe.2026.02.027_bib64","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1016\/j.mito.2012.10.011","article-title":"Is mitochondrial DNA content a potential biomarker of mitochondrial dysfunction?","volume":"13","author":"Malik","year":"2013","journal-title":"Mitochondrion"},{"key":"10.1016\/j.ymthe.2026.02.027_bib65","doi-asserted-by":"crossref","DOI":"10.1101\/pdb.prot087361","article-title":"Measuring Mitochondrial Transmembrane Potential by TMRE Staining","volume":"2016","author":"Crowley","year":"2016","journal-title":"Cold Spring Harb. Protoc."},{"key":"10.1016\/j.ymthe.2026.02.027_bib66","doi-asserted-by":"crossref","first-page":"98","DOI":"10.2144\/000113610","article-title":"Mitochondrial membrane potential probes and the proton gradient: a practical usage guide","volume":"50","author":"Perry","year":"2011","journal-title":"Biotechniques"},{"key":"10.1016\/j.ymthe.2026.02.027_bib67","first-page":"4.25.1","article-title":"Analysis of Mitochondrial Dynamics and Functions Using Imaging Approaches","volume":"4","author":"Mitra","year":"2010","journal-title":"Curr. Protoc. Cell Biol."},{"key":"10.1016\/j.ymthe.2026.02.027_bib68","doi-asserted-by":"crossref","first-page":"D1541","DOI":"10.1093\/nar\/gkaa1011","article-title":"MitoCarta3.0: an updated mitochondrial proteome now with sub-organelle localization and pathway annotations","volume":"49","author":"Rath","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.ymthe.2026.02.027_bib69","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1038\/s41392-023-01547-9","article-title":"Mitochondrial dynamics in health and disease: mechanisms and potential targets","volume":"8","author":"Chen","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"10.1016\/j.ymthe.2026.02.027_bib70","doi-asserted-by":"crossref","DOI":"10.1016\/j.redox.2021.102094","article-title":"Cell cycle induction in human cardiomyocytes is dependent on biosynthetic pathway activation","volume":"46","author":"Abouleisa","year":"2021","journal-title":"Redox Biol."},{"key":"10.1016\/j.ymthe.2026.02.027_bib71","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1093\/stmcls\/sxac016","article-title":"Metabolic Determinants of Cardiomyocyte Proliferation","volume":"40","author":"Mohamed","year":"2022","journal-title":"Stem Cells"},{"key":"10.1016\/j.ymthe.2026.02.027_bib72","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1038\/s42255-020-0169-x","article-title":"Mitochondrial Substrate Utilization Regulates Cardiomyocyte Cell Cycle Progression","volume":"2","author":"Cardoso","year":"2020","journal-title":"Nat. Metab."},{"key":"10.1016\/j.ymthe.2026.02.027_bib73","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1161\/CIRCULATIONAHA.106.671370","article-title":"Adjustable, physiological ventricular restraint improves left ventricular mechanics and reduces dilatation in an ovine model of chronic heart failure","volume":"115","author":"Ghanta","year":"2007","journal-title":"Circulation"},{"key":"10.1016\/j.ymthe.2026.02.027_bib74","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1161\/CIRCULATIONAHA.121.057641","article-title":"Transient Cell Cycle Induction in Cardiomyocytes to Treat Subacute Ischemic Heart Failure","volume":"145","author":"Abouleisa","year":"2022","journal-title":"Circulation"},{"key":"10.1016\/j.ymthe.2026.02.027_bib75","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1161\/CIRCRESAHA.119.314996","article-title":"Physiological Biomimetic Culture System for Pig and Human Heart Slices","volume":"125","author":"Ou","year":"2019","journal-title":"Circ. Res."},{"key":"10.1016\/j.ymthe.2026.02.027_bib76","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41536-025-00389-z","article-title":"Pharmacological or genetic inhibition of LTCC promotes cardiomyocyte proliferation through inhibition of calcineurin activity","volume":"10","author":"Devil\u00e9e","year":"2025","journal-title":"NPJ Regen. Med."},{"key":"10.1016\/j.ymthe.2026.02.027_bib77","doi-asserted-by":"crossref","first-page":"2341","DOI":"10.1161\/01.CIR.94.9.2341","volume":"94","author":"Ryan","year":"1996","journal-title":"Circulation"},{"key":"10.1016\/j.ymthe.2026.02.027_bib78","doi-asserted-by":"crossref","first-page":"3720","DOI":"10.1093\/eurheartj\/ehad191","article-title":"2023 ESC Guidelines for the management of acute coronary syndromes","volume":"44","author":"Byrne","year":"2023","journal-title":"Eur. Heart J."},{"key":"10.1016\/j.ymthe.2026.02.027_bib79","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1161\/01.CIR.0000134791.68010.FA","volume":"110","author":"Antman","year":"2004","journal-title":"Circulation"},{"key":"10.1016\/j.ymthe.2026.02.027_bib80","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1089\/hum.2008.123","article-title":"Adeno-associated virus (AAV) serotype 9 provides global cardiac gene transfer superior to AAV1, AAV6, AAV7, and AAV8 in the mouse and rat","volume":"19","author":"Bish","year":"2008","journal-title":"Hum. Gene Ther."},{"key":"10.1016\/j.ymthe.2026.02.027_bib81","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1097\/HCO.0000000000000386","article-title":"Cardiac gene therapy with adeno-associated virus-based vectors","volume":"32","author":"Chamberlain","year":"2017","journal-title":"Curr. Opin. Cardiol."},{"key":"10.1016\/j.ymthe.2026.02.027_bib82","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.jconrel.2024.06.023","article-title":"Lipid nanoparticle (LNP) mediated mRNA delivery in cardiovascular diseases: Advances in genome editing and CAR T cell therapy","volume":"372","author":"Soroudi","year":"2024","journal-title":"J. Control Release"},{"key":"10.1016\/j.ymthe.2026.02.027_bib83","doi-asserted-by":"crossref","DOI":"10.1093\/cvr\/cvac066.083","article-title":"Modified mRNA delivery to the heart using Lipid Nanoparticles","volume":"118","author":"Labonia","year":"2022","journal-title":"Cardiovasc. Res."},{"key":"10.1016\/j.ymthe.2026.02.027_bib84","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1038\/s41578-021-00358-0","article-title":"Lipid nanoparticles for mRNA delivery","volume":"6","author":"Hou","year":"2021","journal-title":"Nat. Rev. Mater."},{"key":"10.1016\/j.ymthe.2026.02.027_bib85","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1007\/s40291-020-00510-6","article-title":"Current and Emerging Clinical Treatment in Mitochondrial Disease","volume":"25","author":"Tinker","year":"2021","journal-title":"Mol. Diagn. Ther."},{"key":"10.1016\/j.ymthe.2026.02.027_bib86","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1038\/s41580-019-0131-5","article-title":"The next generation of CRISPR\u2013Cas technologies and applications","volume":"20","author":"Pickar-Oliver","year":"2019","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"10.1016\/j.ymthe.2026.02.027_bib87","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1038\/s41587-024-02320-1","article-title":"Epigenome editing technologies for discovery and medicine","volume":"42","author":"McCutcheon","year":"2024","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.ymthe.2026.02.027_bib88","doi-asserted-by":"crossref","first-page":"2104","DOI":"10.1016\/j.ymthe.2025.04.004","article-title":"Gene regulation technologies for gene and cell therapy","volume":"33","author":"Butterfield","year":"2025","journal-title":"Mol. Ther."},{"key":"10.1016\/j.ymthe.2026.02.027_bib89","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1038\/nsmb.2635","article-title":"Translation-dependent displacement of UPF1 from coding sequences causes its enrichment in 3\u2019 UTRs","volume":"20","author":"Z\u00fcnd","year":"2013","journal-title":"Nat. Struct. Mol. Biol."},{"key":"10.1016\/j.ymthe.2026.02.027_bib90","doi-asserted-by":"crossref","first-page":"e85","DOI":"10.1093\/nar\/gkl400","article-title":"Genomic DNA functions as a universal external standard in quantitative real-time PCR","volume":"34","author":"Yun","year":"2006","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.ymthe.2026.02.027_bib91","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1038\/s41587-019-0201-4","article-title":"Graph-based genome alignment and genotyping with HISAT2 and HISAT-genotype","volume":"37","author":"Kim","year":"2019","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.ymthe.2026.02.027_bib92","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol."},{"key":"10.1016\/j.ymthe.2026.02.027_bib93","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/nprot.2008.211","article-title":"Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources","volume":"4","author":"Huang","year":"2009","journal-title":"Nat. Protoc."}],"container-title":["Molecular Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1525001626001139?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1525001626001139?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T12:17:50Z","timestamp":1788178670000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1525001626001139"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6]]},"references-count":93,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["S1525001626001139"],"URL":"https:\/\/doi.org\/10.1016\/j.ymthe.2026.02.027","relation":{},"ISSN":["1525-0016"],"issn-type":[{"value":"1525-0016","type":"print"}],"subject":[],"published":{"date-parts":[[2026,6]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"CRISPR-Cas-based activation of PPARGC1A boosts endogenous mitochondria and enhances cardiac function after myocardial infarction","name":"articletitle","label":"Article Title"},{"value":"Molecular Therapy","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ymthe.2026.02.027","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The Author(s). Published by Elsevier Inc. on behalf of The American Society of Gene and Cell Therapy.","name":"copyright","label":"Copyright"}]}}