Human Gene Expression in Murine Hemopoietic Cells In Vivo
Somatic gene transfer offers the possibility of a new approach in the treatment of human genetic disease. Defects affecting the blood and blood forming tissues are candidates for therapies involving transfer of new genetic information into hemopoietic stem cells. One such defect, adenosine deaminase (ADA) deficiency, is being used as a model in which hemopoietic gene transfer techniques can be developed and evaluated. In this model, gene transfer is mediated by a retroviral vector. Retroviral vectors have been used extensively to deliver information to hemopoietic cells1–14. We have previously reported delivery and expression of human ADA (hADA) sequences in murine hemopoietic progenitors in vitro15 and in vivo16, but were not able to demonstrate long term stability of expression. We describe here the construction and testing of four new vectors, representing the first demonstration of efficient transfer and long term in vivo expression of hADA in murine hemopoietic cells.
KeywordsAdenosine Deaminase Human Genetic Disease Hemopoietic Stem Cell Howard Hughes Medical Institute Human Gene Expression
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- 22.This work was supported by the Howard Hughes Medical Institute (HHMI) and by grants from the NIH (HD21452) and from the Cystic Fibrosis Foundation (R004 7-0351). GRM is the recipient of an Arthritis Foundation post-doctoral fellowship; JWB is an Assistant Investigator and CTC is an Investigator in HHMI. The authors wish to thank Jenny Henkel-Tigges, Dianne Houston-Hawkins, Michelle Rives, Deborah Villalon, and Karen Wager-Smith for technical assistance and Elsa Perez for help in preparation of the manuscript.Google Scholar