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Prepublished online as a Blood First Edition Paper on November 27, 2002; DOI 10.1182/blood-2002-09-2800. This Article Full Text (PDF) All Versions of this Article: 2002-09-2800v1 101/7/2563    most recent Alert me when this article is cited Alert me if a correction is posted 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 Muul, L. M Articles by Candotti, F. Search for Related Content PubMed PubMed Citation Articles by Muul, L. M Articles by Candotti, F. Social Bookmarking                   What's this? Submitted September 13, 2002 Accepted November 11, 2002 Persistence and expression of the adenosine deaminase gene for twelve years and immune reaction to gene transfer components: Long-term results of the first clinical gene therapy trial Linda M Muul*, Laura M Tuschong, Sherry L Soenen, G J Jagadeesh, W J Ramsey, Zhifeng Long, Charles S Carter, Elizabeth K Garabedian, Melinna Alleyne, Margaret Brown, Wendy Bernstein, Shepherd H Schurman, Thomas A Fleisher, Susan F Leitman, Cynthia E Dunbar, R M Blaese, and Fabio Candotti NHGRI, Clinical Gene Therapy Branch, National Institutes of Health, Bethesda, MD, USA NHGRI, Genetics and Molecular Biology Branch, National Institutes of Health, Bethesda, MD, USA Genetic Therapy, Inc, Gaithersburg, MD, USA Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, USA NHGRI, Medical Genetics Branch, National Institutes of Health, Bethesda, MD, USA Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, USA HIV Research Program, Walter Reed Army Medical Center, Washington, DC, USA NHLBI, National Institutes of Health, Bethesda, MD, USA Fund for Inherited Disease Research, Newtown, PA, USA * Corresponding author; email: muul1{at}mail.nih.gov. The first human gene therapy experiment begun in September 1990 employed a retroviral vector containing the human adenosine deaminase (ADA) cDNA to transduce mature peripheral blood lymphocytes from patients with ADA deficiency, an inherited disorder of immunity. Two patients who had been treated with intramuscular injections of pegylated bovine ADA (PEG-ADA) for 2-4 years were enrolled in this trial and each received a total of approximately 1011 cells in 11 or 12 infusions over a period of about two years. No adverse events were observed. During and after treatment, the patients continued to receive PEG-ADA, although at a reduced dose. Ten years after the last cell infusion, ~20% of the first patient's lymphocytes still carry and express the retroviral gene, indicating that the effects of gene transfer can be remarkably long lasting. On the contrary, the persistence of gene-marked cells is very low (<0.1%) and no expression of the transgene is detectable in lymphocytes from the second patient who developed persisting antibodies to components of the gene transfer system. Data collected from these original patients have provided novel information about the longevity of T lymphocytes in humans and persistence of gene expression in vivo from vectors driven by the Moloney murine leukemia virus long terminal repeat (LTR) promoter. This long-term follow-up has also provided unique evidence supporting the safety of retroviral-mediated gene transfer and illustrates clear examples of both the potential and the pitfalls of gene therapy in humans. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. W. Nienhuis Development of gene therapy for blood disorders Blood, May 1, 2008; 111(9): 4431 - 4444. [Abstract] [Full Text] [PDF] S. Wilkie, G. 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