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Prepublished online as a Blood First Edition Paper on May 22, 2003; DOI 10.1182/blood-2003-01-0167. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-01-0167v1 102/6/2038    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Powell, J. S. Articles by Hurst, D. Search for Related Content PubMed PubMed Citation Articles by Powell, J. S. Articles by Hurst, D. Related Collections Hemostasis, Thrombosis, and Vascular Biology Gene Therapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 September 2003, Vol. 102, No. 6, pp. 2038-2045 GENE THERAPY Phase 1 trial of FVIII gene transfer for severe hemophilia A using a retroviral construct administered by peripheral intravenous infusion Jerry S. Powell, Margaret V. Ragni, Gilbert C. White, II, Jeanne M. Lusher, Carol Hillman-Wiseman, Tom E. Moon, Veronica Cole, Sandhya Ramanathan-Girish, Holger Roehl, Nancy Sajjadi, Douglas J. Jolly, and Deborah Hurst From the University of California at Davis, Sacramento; the University of Pittsburgh (UP), General Clinical Research Center, PA; the University of North Carolina (UNC), Chapel Hill; Wayne State University, Detroit, MI; Chiron, Emeryville, CA; the Chiron Center for Gene Therapy, San Diego, CA; Cell Genesys, San Diego, CA; Biomedica, San Diego, CA; and Sajjadi Associates, Encinitas, CA. In a phase 1 dose escalation study, 13 subjects with hemophilia A received by peripheral intravenous infusion a retroviral vector carrying a B-domain–deleted human factor VIII (hFVIII) gene. Infusions were well tolerated. Tests for replication competent retrovirus have been negative. Polymerase chain reaction (PCR) analyses demonstrate the persistence of vector gene sequences in peripheral blood mononuclear cells in 3 of 3 subjects tested. Factor VIII was measured in serial samples using both a one-stage clotting assay and a chromogenic assay. While no subject had sustained FVIII increases, 9 subjects had FVIII higher than 1% on at least 2 occasions 5 or more days after infusion of exogenous FVIII, with isolated levels that ranged from 2.3% to 19%. Pharmacokinetic parameters of exogenous FVIII infused into subjects 13 weeks after vector infusion showed an increased half-life (T1/2; P < .02) and area under the curve (AUC, P < .04) compared with prestudy values. Bleeding frequency decreased in 5 subjects compared with historical rates. These results demonstrate that this retroviral vector (hFVIII(V)) is safe and, in some subjects, persists more than a year in peripheral blood mononuclear cells, with measurable factor VIII levels and with increased available FVIII activity (increased T1/2 and AUC) after infusion of exogenous FVIII concentrate. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: H. Matsui, M. Shibata, B. Brown, A. Labelle, C. 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