{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T08:23:31Z","timestamp":1774686211840,"version":"3.50.1"},"reference-count":74,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T00:00:00Z","timestamp":1753142400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T00:00:00Z","timestamp":1753142400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2026,2]]},"abstract":"\n Abstract<\/jats:title>\n \n During myocardial infarction, native myocardium is replaced by a fibrous scar, impairing cardiac pump function and leading to potentially life\u2010threatening ventricular tachycardias. Gene therapy\u2010based targeting of the cardiac scar is essential for short\u2010 and long\u2010term treatment of post\u2010infarct sequelae. However, there are currently no effective methods to target and transduce cardiac (myo)fibroblasts (FB)\n in vivo<\/jats:italic>\n . Therefore, Moloney murine leukaemia virus (MMLV) encoding for the fluorescent reporter mCherry complexed with magnetic nanoparticles (MNP) in combination with magnetic steering was tested. This approach strongly increased the transduction rate of FB by four\u2010fold\n in vitro<\/jats:italic>\n . Additionally, injection of MMLV\/MNP complexes into the forming scar during exposure of the heart to a magnetic field to increase virus dwell\u2010time 3\u00a0days after left ventricular cryo\u2010injury, a time when FB proliferation in the infarct peaks, yielded efficient transduction of resident FB. We further assessed the functional impact of overexpressing the gap junction protein connexin 43 (Cx43). MMLV\u2010mediated Cx43 overexpression (MMLV\u2010Cx43) in FB increased the formation of functional gap junctions\n in vitro<\/jats:italic>\n and substantially lowered post\u2010cryo\u2010injury ventricular tachycardia incidence (by 50%), as demonstrated by\n in vivo<\/jats:italic>\n electrophysiological testing 2 and 8\u00a0weeks after MMLV\/MNP injection into the lesion. This anti\u2010arrhythmic effect was probably the result of a decrease in the heterogeneity of conduction around and across the scar, as observed by optical mapping in isolated hearts overexpressing Cx43. Thus, MMLV\/MNP complexes combined with magnetic steering offer an efficient strategy for targeting and transducing FB\n in vitro<\/jats:italic>\n and\n in vivo<\/jats:italic>\n , allowing modulation of the functional properties of cardiac scars.\n \n \n image<\/jats:alt-text>\n <\/jats:graphic>\n <\/jats:boxed-text>\n <\/jats:p>\n <\/jats:sec>\n \n Key points<\/jats:title>\n \n \n \n \n Genetic targeting and efficient transduction of (myo)fibroblasts (FB)\n in vivo<\/jats:italic>\n are necessary to modify the properties of cardiac scars for therapeutic benefit. However, this has proven highly inadequate because of a lack of suitable viral vectors.\n <\/jats:p>\n <\/jats:list-item>\n \n \n We complexed Moloney murine leukaemia virus (MMLV) with magnetic nanoparticles (MNP) and applied a magnetic field to achieve prominent\n in vitro<\/jats:italic>\n transduction of FB.\n <\/jats:p>\n <\/jats:list-item>\n \n \n Magnet\u2010assisted\n in vivo<\/jats:italic>\n injections of MMLV\/MNP complexes into the developing scar enabled efficient transduction of cardiac tissue\u2010resident FB.\n <\/jats:p>\n <\/jats:list-item>\n \n \n MMLV\u2010Cx43\u2010based overexpression of connexin 43 increased the density of functional gap junctions in FB\n in vitro<\/jats:italic>\n . Following direct injection of the virus into the developing cardiac scar in a murine cryo\u2010lesion model, electrophysiological\n in vivo<\/jats:italic>\n testing showed that the incidence of ventricular tachycardia was reduced by 50% at 2 and 8\u00a0weeks post\u2010treatment with MMLV.\n <\/jats:p>\n <\/jats:list-item>\n \n Our approach enables efficient targeting and transduction of FB in the cardiac scar, providing a blueprint for translation.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1113\/jp288020","type":"journal-article","created":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T23:35:26Z","timestamp":1753227326000},"page":"1708-1735","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Efficient\n in vivo<\/i>\n targeting of the myocardial scar using Moloney murine leukaemia virus complexed with 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