Nature Medicine
1, 1017 - 1023 (1995)
doi:10.1038/nm1095-1017
Engraftment of gene−modified umbilical cord blood cells in neonates with adenosine deaminase deficiencyDonald B. Kohn1, 9, Kenneth I. Weinberg1, Jan A. Nolta1, Linda N. Heiss1, Carl Lenarsky1, Gay M. Crooks1, Mary E. Hanley1, Geralyn Annett1, Judith S. Brooks1, Anthony El-Khoureiy1, Kim Lawrence1, Susie Wells1, Robert C. Moen2, John Bastian3, Debora E. Williams-Herman4, Melissa Elder4, Diane Wara4, Thomas Bowen5, Michael S. Hershfield6, Craig A. Mullen7, 8, R. Michael Blaese7
& Robertson Parkman1
1Division of Research Immunology/Bone Marrow Transplantation, Childrens Hospital, Los Angeles, University of Southern California School of Medicine, 4650 Sunset Boulevard, Los Angeles, California 90027, USA
2Genetic Therapy, Inc., 938 ClopperRoad, Gaithersburg, Maryland 20878, USA
3Children's Hospital and Health Center, San Diego, California 92123, USA
4Department of Pediatrics, University of California at San Francisco, San Francisco, California 94143, USA
51842 Oak Bay, Victoria, BC, Canada, V8R 1C2
6Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA
7National Center for Human Genome Research, National Institutes of Health, Building 49, Room 2A03, 4900 Convent Drive, Bethesda, Maryland 20892-4430, USA
8Present address: Department of Experimental Pediatrics, Univeristy of Texas M.D. Anderson Cancer Center, Box 88, Room AC6.004, 1515 Holcombe Boulevard, Houston, Texas, 77030, USA
9Correspondence should be addressed to D.B.K. Haematopoietic stem cells in umbilical cord blood are an attractive target for gene therapy of inborn errors of metabolism. Three neonates with severe combined immunodeficiency were treated by retroviral−mediated transduction of the CD34+ cells from their umbilical cord blood with a normal human adenosine deaminase complementary DNA followed by autologous transplantation. The continued presence and expression of the introduced gene in leukocytes from bone marrow and peripheral blood for 18 months demonstrates that umbilical cord blood cells may be genetically modified with retroviral vectors and engrafted in neonates for gene therapy.
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