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Adv."],"published-print":{"date-parts":[[2026,3,20]]},"abstract":"<jats:p>\n                    Despite continued progress, therapies to augment contractile function and prevent arrhythmias in patients with heart failure remain limited. Here, we present a two-pronged gene therapy approach that simultaneously augments peak Na\n                    <jats:sup>+<\/jats:sup>\n                    current and Ca\n                    <jats:sup>2+<\/jats:sup>\n                    transient amplitude in cardiomyocytes (CMs) to alleviate heart failure pathogenesis. Using in vitro engineered neonatal rat heart tissues, ex vivo adult mouse CMs, and in silico rabbit CMs, we show that expression of prokaryotic Na\n                    <jats:sup>+<\/jats:sup>\n                    channels (BacNa\n                    <jats:sub>v<\/jats:sub>\n                    ) dose-dependently enhances Ca\n                    <jats:sup>2+<\/jats:sup>\n                    transients and contractility of CMs by modulating Na\n                    <jats:sup>+<\/jats:sup>\n                    \/Ca\n                    <jats:sup>2+<\/jats:sup>\n                    exchanger activity and increasing sarcoplasmic reticulum Ca\n                    <jats:sup>2+<\/jats:sup>\n                    stores. In mice, adeno-associated virus 9 (AAV9)\u2013mediated BacNa\n                    <jats:sub>v<\/jats:sub>\n                    therapy rescues contractile deficit, prevents arrhythmias, and improves transcriptomic dysregulation in a pressure-overload induced model of chronic heart failure. We further establish the safety of long-term systemic delivery of AAV9-BacNa\n                    <jats:sub>v<\/jats:sub>\n                    in mice. Collectively, these studies support the translational promise of BacNa\n                    <jats:sub>v<\/jats:sub>\n                    gene delivery as an effective therapy for electrical and contractile dysfunction in heart failure.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.ady4551","type":"journal-article","created":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T18:01:06Z","timestamp":1774029666000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Regulation of sodium\/calcium homeostasis by BacNa\n                    <sub>v<\/sub>\n                    gene therapy rescues cardiac dysfunction in chronic heart failure"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7341-2781","authenticated-orcid":true,"given":"Tianyu","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, Duke University, Durham, NC, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3574-0485","authenticated-orcid":true,"given":"Yongwu","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Duke University, Durham, NC, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5120-0470","authenticated-orcid":true,"given":"Robin M.","family":"Perelli","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Pediatrics, Duke University School of Medicine, Durham, NC, USA."},{"name":"Department of Cell Biology, Duke University School of Medicine, Durham, NC, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yiu Yan","family":"Siu","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Duke University, Durham, NC, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Tornatore","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Duke University, Durham, NC, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Josue","family":"Nataren","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Duke University, Durham, NC, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5280-8894","authenticated-orcid":true,"given":"Xixian","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Duke University, Durham, NC, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9432-8186","authenticated-orcid":true,"given":"Sophia","family":"DeLuca","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Duke University School of Medicine, Durham, NC, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2237-9483","authenticated-orcid":true,"given":"Donald M.","family":"Bers","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of California, Davis, CA, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Craig","family":"Henriquez","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Duke University, Durham, NC, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1878-9631","authenticated-orcid":true,"given":"Andrew P.","family":"Landstrom","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Pediatrics, Duke University School of Medicine, Durham, NC, USA."},{"name":"Department of Cell Biology, Duke University School of Medicine, Durham, NC, 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