{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T04:49:12Z","timestamp":1773722952905,"version":"3.50.1"},"reference-count":25,"publisher":"American Society of Hematology","issue":"21","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,5,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Sustained expression of therapeutic factor IX (FIX) levels has been achieved after adeno-associated viral (AAV) vector-based gene therapy in patients with hemophilia B. Nevertheless, patients are still at risk of vector dose-limiting toxicity, particularly liver inflammation, justifying the need for more efficient vectors and a lower dosing regimen. A novel increased potency FIX (designated as CB 2679d-GT), containing 3 amino acid substitutions (R318Y, R338E, T343R), significantly outperformed the R338L-Padua variant after gene therapy. CB 2679d-GT demonstrated a statistically significant approximately threefold improvement in clotting activity when compared with R338L-Padua after AAV-based gene therapy in hemophilic mice. Moreover, CB 2679d-GT gene therapy showed significantly reduced bleeding time (approximately fivefold to eightfold) and total blood loss volume (approximately fourfold) compared with mice treated with the R338L-Padua, thus achieving more rapid and robust hemostatic correction. FIX expression was sustained for at least 20 weeks with both CB 2679d-GT and R338L-Padua whereas immunogenicity was not significantly increased. This is a novel gene therapy study demonstrating the superiority of CB 2679d-GT, highlighting its potential to obtain higher FIX activity levels and superior hemostatic efficacy following AAV-directed gene therapy in hemophilia B patients than what is currently achievable with the R338L-Padua variant.<\/jats:p>","DOI":"10.1182\/blood.2020006005","type":"journal-article","created":{"date-parts":[[2021,3,18]],"date-time":"2021-03-18T22:17:02Z","timestamp":1616105822000},"page":"2902-2906","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":13,"title":["Gene therapy for hemophilia B using CB 2679d-GT: a novel factor IX variant with higher potency than factor IX Padua"],"prefix":"10.1182","volume":"137","author":[{"given":"Nisha","family":"Nair","sequence":"first","affiliation":[{"name":"Department of Gene Therapy and Regenerative Medicine, Vrije Universiteit Brussel, Brussels, Belgium;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dries","family":"De Wolf","sequence":"additional","affiliation":[{"name":"Department of Gene Therapy and Regenerative Medicine, Vrije Universiteit Brussel, Brussels, Belgium;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Phuong Anh","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Gene Therapy and Regenerative Medicine, Vrije Universiteit Brussel, Brussels, Belgium;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Quang Hong","family":"Pham","sequence":"additional","affiliation":[{"name":"Department of Gene Therapy and Regenerative Medicine, Vrije Universiteit Brussel, Brussels, Belgium;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ermira","family":"Samara-Kuko","sequence":"additional","affiliation":[{"name":"Department of Gene Therapy and Regenerative Medicine, Vrije Universiteit Brussel, Brussels, 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