Gene transfer into nonhuman primate CD34+CD11b- bone marrow progenitor cells capable of repopulating lymphoid and myeloid lineages

Human Gene Therapy
V W van BeusechemD Valerio

Abstract

We investigated whether rhesus monkey CD34+CD11b- hematopoietic stem cells can be transduced with recombinant retroviruses carrying the human adenosine deaminase (hADA) gene by co-cultivation with a virus-producing cell line. Following autologous transplantation, polymerase chain reaction (PCR) analysis on peripheral blood mononuclear cells and granulocytes showed that the hADA-retrovirus was present in approximately 0.1% of the cells for at least 400 days post transplantation in 2 monkeys. Bone marrow that was harvested 16 months after transplantation carried ADA-overexpressing myeloid progenitor cells capable of in vitro colony formation. In addition, hADA activity could be demonstrated in T lymphocytes that were harvested 9 months post transplantation. Thus, in vitro transduction of CD34+CD11b- cells led to long-term repopulation of the hematopoietic system with transduced cells of lymphoid and myeloid lineages expressing the hADA gene. To investigate whether infusion of virus-producing cells into a rhesus monkey undergoing autologous bone marrow transplantation could lead to in vivo transfer of the recombinant retrovirus, 1 monkey was infused with CD34+CD11b- bone marrow cells (BMC) and a large quantity of virus-producing c...Continue Reading

References

Aug 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·V W van BeusechemD Valerio
Sep 1, 1992·The Journal of Experimental Medicine·D J KesslerG E Sonenshein
Nov 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·B LimD A Williams
May 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·R J KaufmanR E Kellems

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Citations

May 7, 1997·Transfusion Science·B Péault, P Charbord
Aug 10, 1999·Critical Reviews in Oncology/hematology·C LutzkoA K Stewart
Sep 10, 1996·Human Gene Therapy·V W Van Beusechem, D Valerio
Feb 1, 1997·Journal of Medical Primatology·S W WongE P Bergquam
Sep 1, 2004·Molecular Therapy : the Journal of the American Society of Gene Therapy·Peter A HornHans-Peter Kiem

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