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

V W Van Beusechem, J A Bart-Baumeister, T A Bakx, L C Kaptein, R J Levinsky, D Valerio

Research output: Contribution to journalArticleAcademicpeer-review

24 Citations (Scopus)


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 cells. Few provirus-carrying cells could temporarily be detected in this animal. This shows that in vivo gene transfer into a regenerating hemopoietic system can occur, albeit at very low efficiency.

Original languageEnglish
Pages (from-to)295-305
Number of pages11
JournalHuman gene therapy
Issue number3
Publication statusPublished - Mar 1994


  • Adenosine Deaminase/genetics
  • Animals
  • Antigens, CD
  • Antigens, CD34
  • CD11 Antigens
  • Cell Differentiation
  • Cell Line
  • DNA Replication
  • Gene Transfer Techniques
  • Hematopoietic Stem Cell Transplantation
  • Hematopoietic Stem Cells/cytology
  • Humans
  • Macaca mulatta
  • T-Lymphocytes/cytology

Cite this