Lentivirus-mediated gene transfer into hematopoietic repopulating cells in baboons

P. A. Horn, J. C. Morris, A. A. Bukovsky, R. G. Andrews, L. Naldini, Peter Kurre, H. P. Kiem

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Efficient transduction of hematopoietic stem cells is a prerequisite for successful hematopoietic stem cell gene therapy. Oncoretroviral vectors are the most widely used vectors for hematopoietic gene therapy studies. However, these vectors require cell division, and thus efficient transduction of quiescent stem cells has been difficult to achieve. Lentiviral vectors can transduce non-dividing cells and therefore may be more efficient in transducing quiescent hematopoietic stem cells. We have used a competitive repopulation assay in the baboon to compare transduction of hematopoietic repopulating cells by lentiviral and oncoretroviral vectors. Baboon CD34-enriched marrow cells were transduced in the presence or absence of multiple hematopoietic growth factors using a short, 2-day, transduction protocol. Here, we show that efficient lentiviral transduction of hematopoietic repopulating cells was only achieved when cells were transduced in the presence of multiple growth factors. Using these conditions, up to 8.6% of hematopoietic repopulating cells were genetically modified by the lentiviral vector more than 1 year after transplant. Interestingly, the number of lentivirally marked cells increased over time in three of four animals. In conclusion, these results suggest that lentiviral vectors are able to tranduce multilineage hematopoietic stem cells, and thus, may provide an alternative vector system for clinical stem cell gene therapy applications.

Original languageEnglish (US)
Pages (from-to)1464-1471
Number of pages8
JournalGene Therapy
Volume9
Issue number21
DOIs
StatePublished - Nov 2002
Externally publishedYes

Fingerprint

Lentivirus
Papio
Hematopoietic Stem Cells
Genes
Genetic Therapy
Cell- and Tissue-Based Therapy
Intercellular Signaling Peptides and Proteins
Stem Cells
Cell Division
Bone Marrow
Transplants

Keywords

  • Gene transfer
  • Lentiviral vectors
  • Oncoretroviral vectors
  • Stem cells

ASJC Scopus subject areas

  • Genetics

Cite this

Horn, P. A., Morris, J. C., Bukovsky, A. A., Andrews, R. G., Naldini, L., Kurre, P., & Kiem, H. P. (2002). Lentivirus-mediated gene transfer into hematopoietic repopulating cells in baboons. Gene Therapy, 9(21), 1464-1471. https://doi.org/10.1038/sj.gt.3301820

Lentivirus-mediated gene transfer into hematopoietic repopulating cells in baboons. / Horn, P. A.; Morris, J. C.; Bukovsky, A. A.; Andrews, R. G.; Naldini, L.; Kurre, Peter; Kiem, H. P.

In: Gene Therapy, Vol. 9, No. 21, 11.2002, p. 1464-1471.

Research output: Contribution to journalArticle

Horn, PA, Morris, JC, Bukovsky, AA, Andrews, RG, Naldini, L, Kurre, P & Kiem, HP 2002, 'Lentivirus-mediated gene transfer into hematopoietic repopulating cells in baboons', Gene Therapy, vol. 9, no. 21, pp. 1464-1471. https://doi.org/10.1038/sj.gt.3301820
Horn, P. A. ; Morris, J. C. ; Bukovsky, A. A. ; Andrews, R. G. ; Naldini, L. ; Kurre, Peter ; Kiem, H. P. / Lentivirus-mediated gene transfer into hematopoietic repopulating cells in baboons. In: Gene Therapy. 2002 ; Vol. 9, No. 21. pp. 1464-1471.
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