Stage Ⅰ Clinical Trial of Gene Therapy for Hemophilia B

This paper describes the first human gene therapy trial for hemophilia B. Retroviruses were used to introduce human factor Ⅸ into autologous, primary human skin fibroblasts from the patients. Recombinant retroviral vector containing human FIX cDNA driven by viral LTR promoter (XL-Ⅸ) and double-copy retroviral vector driven by human cytomegalovirus enhancer-promoter (N2CMV-Ⅸ)were constructed. After the safety assessment, including soft-agar test, cell morphology observation, analysis of endotoxin, chromosome karyotype, allergic reaction test, nude mice test, routine pathological test, electromicroscopic analysis, and virus detection by PCR, etc., the engineered cells were pooled and embedded in collagen mixture, autologously injected into the patients respectively. The concentration of human FIX protein of Patient 1 increased from 71 ng/ml to 220 ng/ml, witha maximum level of 245 ng/ml. The expression of FIX has lasted for 6 months at the time of writing. The clotting activity also increased from 2.9%