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Lentivirus-mediated gene transfer into hematopoietic repopulating cells in baboons
P A Horn1, J C Morris, A A Bukovsky
1Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Gene Therapy
|October 16, 2002
Summary
Lentiviral vectors efficiently transduced hematopoietic stem cells when combined with growth factors, offering a promising alternative for gene therapy. These modified cells persisted long-term in baboons, showing potential for clinical applications.
Area of Science:
- Hematology
- Gene Therapy
- Molecular Biology
Background:
- Hematopoietic stem cell gene therapy requires efficient stem cell transduction.
- Oncoretroviral vectors necessitate cell division, limiting transduction of quiescent stem cells.
- Lentiviral vectors can transduce non-dividing cells, potentially improving stem cell gene therapy.
Purpose of the Study:
- To compare the transduction efficiency of lentiviral and oncoretroviral vectors in hematopoietic repopulating cells.
- To evaluate the potential of lentiviral vectors for clinical stem cell gene therapy.
Main Methods:
- A competitive repopulation assay was performed in baboons.
- Baboon CD34-enriched marrow cells were transduced with lentiviral or oncoretroviral vectors.
- Transduction was conducted with or without hematopoietic growth factors over a 2-day period.
Main Results:
- Efficient lentiviral transduction of hematopoietic repopulating cells was achieved only with multiple growth factors.
- Up to 8.6% of repopulating cells were genetically modified by lentiviral vectors over a year post-transplant.
- Lentivirally marked cell numbers increased over time in most animals.
Conclusions:
- Lentiviral vectors can transduce multilineage hematopoietic stem cells.
- Lentiviral vectors represent a viable alternative vector system for clinical stem cell gene therapy.