{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T11:44:37Z","timestamp":1791027877603,"version":"4.1.0"},"reference-count":52,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2004,11,1]],"date-time":"2004-11-01T00:00:00Z","timestamp":1099267200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Gene Medicine"],"published-print":{"date-parts":[[2005,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Hemophilia A treatment relies on costly factor VIII (FVIII) replacement that may transmit iatrogenic viral diseases. Viral vectors and cell implants are being developed as improvements. We investigated <jats:italic>in vivo<\/jats:italic> electroporation of naked DNA as a safe and simple method for correcting FVIII deficiency.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>B\u2010domain\u2010deleted murine FVIII cDNA expression plasmids were constructed with CMV and elongation factor 1\u03b1 promoters for characterisation in murine C2C12 myoblasts. The construct conferring highest <jats:italic>in vitro<\/jats:italic> FVIII secretion was electroporated into skeletal muscle of FVII null mice <jats:italic>in vivo<\/jats:italic> for phenotypic correction using a protocol that minimised tissue injury.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>B\u2010domain\u2010deleted murine FVIII cDNA plasmids induced FVIII secretion from stably transfected C2C12 myoblasts (0.54 \u00b1 0.20 mU\/day\/10<jats:sup>5<\/jats:sup> cells). Phenotypic correction of hemophilic mice was more consistently achieved using a protocol for <jats:italic>in vivo<\/jats:italic> electroporation of gastrocnemius muscle with FVIII cDNA that reduced tissue injury by the use of plate electrodes, hyaluronidase pre\u2010treatment and lower field strength. This technique was associated with &lt;10% muscle necrosis. Activated partial thromboplastin time decreased from 51.4 \u00b1 3.3 to 34.7 \u00b1 1.1 (mean \u00b1 s.e.m.) seconds (<jats:italic>p<\/jats:italic> = 0.0004) following <jats:italic>in vivo<\/jats:italic> electroporation (0.1 mg plasmid\/limb; 8 \u00d7 20 ms pulses, 175 V\/cm, 1 Hz) of hemophilic mice. All hemophilic mice (8\/8) survived hemostatic challenge after muscle electroporation with FVIII cDNA, whereas all (9\/9) untreated hemophilic mice died. Plasmid DNA was detectable only in electroporated muscle and not in all other organs tested, including gonads.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p><jats:italic>In vivo<\/jats:italic> intramuscular electroporation of naked FVIII plasmid successfully corrects murine hemophilia. Copyright \u00a9 2004 John Wiley &amp; Sons, Ltd.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jgm.683","type":"journal-article","created":{"date-parts":[[2004,11,13]],"date-time":"2004-11-13T00:47:26Z","timestamp":1100306846000},"page":"494-505","source":"Crossref","is-referenced-by-count":25,"title":["FVIII gene delivery by muscle electroporation corrects murine hemophilia A"],"prefix":"10.1002","volume":"7","author":[{"given":"Yun Chau","family":"Long","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Jaichandran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liam Pock","family":"Ho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sim Leng","family":"Tien","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soo 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