{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T05:52:31Z","timestamp":1775713951824,"version":"3.50.1"},"reference-count":58,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T00:00:00Z","timestamp":1775692800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>\n                    Hemophilia A, an X-linked bleeding disorder caused by factor VIII (FVIII) deficiency, necessitates lifelong factor replacement therapy with high treatment burden. To explore a non-viral alternative, we evaluated minicircle DNA carrying the FVIII-E1984V mutation\u2014engineered for improved stability and activity\u2014as a gene therapy for sustained coagulation correction. Mini-circle DNA constructs (with the bacterial backbone excised) encoding either wild-type FVIII or E1984V-FVIII were delivered\n                    <jats:italic>via<\/jats:italic>\n                    hydrodynamic tail vein injection into FVIII-KO mice, a typical murine model of hemophilia A. Coagulation outcomes (aPTT, FVIII activity, tail-clip assay) and transgene persistence were monitored over 26 weeks. Minicircle DNA delivery demonstrated higher transfection efficiency\n                    <jats:italic>in vitro<\/jats:italic>\n                    and sustained coagulation improvement\n                    <jats:italic>in vivo<\/jats:italic>\n                    for at least 26 weeks, markedly exceeding the short durability of conventional FVIII infusion (days\n                    <jats:italic>versus<\/jats:italic>\n                    weeks). Furthermore, exogenous FVIII DNA and RNA persisted in hepatocytes without evidence of hepatotoxicity. These findings highlight minicircle DNA\u2013based FVIII gene therapy as a promising strategy for hemophilia A. Future studies will focus on optimizing vector design for sustained expression, advancing toward clinical translation.\n                  <\/jats:p>","DOI":"10.3389\/fphar.2026.1742144","type":"journal-article","created":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T05:20:22Z","timestamp":1775712022000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Non-viral gene therapy for hemophilia A: long-term outcomes of minicircle FVIII delivery in a mouse model"],"prefix":"10.3389","volume":"17","author":[{"given":"Yung-Tsung","family":"Kao","sequence":"first","affiliation":[{"name":"Department of Life Sciences, and Doctorial Program in Translational Medicine, National Chung Hsing University","place":["Taichung, Taiwan"]},{"name":"Ph.D. Program in Tissue Engineering and Regenerative Medicine, National Health Research Institutes and National Chung Hsing University","place":["Taichung, Taiwan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chih-Ching","family":"Yen","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, and Doctorial Program in Translational Medicine, National Chung Hsing University","place":["Taichung, Taiwan"]},{"name":"Department of Internal Medicine, China Medical University Hospital, and China Medical University","place":["Taichung, Taiwan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gary","family":"Ro-Lin Chang","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, and Doctorial Program in Translational Medicine, National Chung Hsing University","place":["Taichung, Taiwan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hsin-Tse","family":"Chiang","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, and Doctorial Program in Translational Medicine, National Chung Hsing University","place":["Taichung, Taiwan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jen-Kun","family":"Chen","sequence":"additional","affiliation":[{"name":"Ph.D. Program in Tissue Engineering and Regenerative Medicine, National Health Research Institutes and National Chung Hsing University","place":["Taichung, Taiwan"]},{"name":"Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes","place":["Tainan, Taiwan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muhammad","family":"Sufian","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology and Biotechnology (IMBB), The University of Lahore","place":["Lahore, Pakistan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"I.-Chien","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, and Doctorial Program in Translational Medicine, National Chung Hsing University","place":["Taichung, Taiwan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shang-Hsun","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Physiology, Institute of Basic Medical Sciences, National Cheng Kung University","place":["Tainan, Taiwan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chuan-Mu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, and Doctorial Program in Translational Medicine, National Chung Hsing University","place":["Taichung, Taiwan"]},{"name":"Ph.D. Program in Tissue Engineering and Regenerative Medicine, National Health Research Institutes and National Chung Hsing University","place":["Taichung, Taiwan"]},{"name":"The iEGG and Animal Biotechnology Center, Rong Hsing Research Center for Translational Medicine, National Chung Hsing University","place":["Taichung, Taiwan"]},{"name":"Center for General Educational, National Quemoy University","place":["Kinmen, Taiwan"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"612594","DOI":"10.3389\/fceng.2020.612594","article-title":"Minicircle Biopharmaceuticals\u2013An overview of purification strategies","volume":"2","author":"Alves","year":"2021","journal-title":"Front. 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