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Blood, 1 October 2005, Vol. 106, No. 7, pp. 2280-2286. Prepublished online as a Blood First Edition Paper on March 29, 2005; DOI 10.1182/blood-2004-11-4174. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-11-4174v1 106/7/2280    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 Lippin, Y. Articles by Galun, E. Search for Related Content PubMed PubMed Citation Articles by Lippin, Y. Articles by Galun, E. Related Collections Gene Therapy Hematopoiesis Red Cells Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  GENE THERAPY Human erythropoietin gene therapy for patients with chronic renal failure Yitzhak Lippin, Michal Dranitzki-Elhalel, Einat Brill-Almon, Chava Mei-Zahav, Sarah Mizrachi, Yael Liberman, Adrian Iaina, Eli Kaplan, Eduardo Podjarny, Evelyne Zeira, Menahem Harati, Nicole Casadevall, Noam Shani, and Eithan Galun From the Department of Plastic Surgery, Rambam Medical Center, Haifa, Israel; the Department of Medicine, Hadassah-Hebrew University Hospital, Jerusalem, Israel; Medgenics, Biogenics, Misgav, Israel; the Goldyne Savad Institute of Gene Therapy, Hadassah-Hebrew University Hospital, Jerusalem, Israel; the Department of Nephrology, Sourasky Medical Center, Tel Aviv, Israel; Medical Clinic, Herzliah, Israel; the Laboratoire d'Hematologie, Hôtel Dieu, Paris, France; and Institut National de la Santé et de la Recherche Médicale (INSERM) 362, Paris, France. Gene therapy holds a major promise. However, until now, this promise was fulfilled only in few cases, in rare genetic diseases. One very common clinical condition is anemia. Patients with anemia of chronic renal failure are treated with erythropoietin. The objective of this study was to develop a therapeutic platform for serum-secreted proteins like erythropoietin. We developed a tissue protein factory based on dermal cores (Biopump) harvested and implanted autologously. In this study, an adenovector was designed to express the human erythropoietin under the control of the cytomegalovirus (CMV) promoter. This vector transduced the harvested dermal cores ex vivo. The transduced cores were implanted, and erythropoietin and reticulocyte counts were measured. Dermal cores were harvested from 13 patients with chronic renal failure, and implantation was performed in 10. There were no significant drug-related side effects to this procedure. Erythropoietin serum levels increased significantly to therapeutic levels from day 1 after implantation reaching a peak during the first week of follow-up. The expression period was transient for up to 14 days. The rise of erythropoietin was followed by a transient significant increase in reticulocyte counts. The decrease of erythropoietin expression coincided with a significant dermal infiltrate of CD8 cytotoxic T cells. Antierythropoietin antibodies were not detected until day 90 following implantation. Implantation of dermal cores ex vivo transduced with human genes could eventually be used in the clinical setting to express therapeutic serum proteins. However, nonimmunogenic delivery system should be tested as gene vehicles. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A R Lyon, M Sato, R J Hajjar, R J Samulski, and S E Harding Gene therapy: targeting the myocardium Heart, January 1, 2008; 94(1): 89 - 99. [Abstract] [Full Text] [PDF] I. C. Macdougall Novel Erythropoiesis-Stimulating Agents: A New Era in Anemia Management Clin. J. Am. Soc. Nephrol., January 1, 2008; 3(1): 200 - 207. [Abstract] [Full Text] [PDF] M. M. Hsieh, N. S. Linde, A. Wynter, M. Metzger, C. Wong, I. Langsetmo, A. Lin, R. Smith, G. P. Rodgers, R. E. Donahue, et al. HIF prolyl hydroxylase inhibition results in endogenous erythropoietin induction, erythrocytosis, and modest fetal hemoglobin expression in rhesus macaques Blood, September 15, 2007; 110(6): 2140 - 2147. [Abstract] [Full Text] [PDF] N. Eliopoulos, R. F. Gagnon, M. Francois, and J. Galipeau Erythropoietin Delivery by Genetically Engineered Bone Marrow Stromal Cells for Correction of Anemia in Mice with Chronic Renal Failure J. Am. Soc. Nephrol., June 1, 2006; 17(6): 1576 - 1584. [Abstract] [Full Text] [PDF]

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