Abstract
Hematopoietic stem cells (HSCs) are a promising target for gene therapy, however, the low efficiencies of gene transfer using currently available vectors face practical limitations. We have recently developed a novel and efficient gene transfer agent, namely recombinant Sendai virus (SeV), and we have here characterized SeV-mediated gene transfer to human cord blood (CB) HSCs and primitive progenitor cells (PPC) using the jelly fish green fluorescent protein (GFP) gene. Even at a relatively low titer (10 multiplicity of infections), SeV achieved highly efficient GFP expression in CB CD34+ cells (85.5 ± 5.8%), as well as more immature CB progenitor cells, CD34+AC133+ (88.2 ± 3.7%) and CD34+CD38- (84.6 ± 5.7%) cells, without cytokines prestimulation, that was a clear contrast to the features of gene transfer using retroviruses. SeV-mediated gene transfer was not seriously affected by the cell cycle status. In vitro cell differentiation studies revealed that gene transfer occurred in progenitor cells of all lineages (GM-CFU, 73.0 ± 11.1%; BFU-E, 24.7 ± 4.0%; Mix-CFU, 59 ± 4.0%; and total, 50.0 ± 7.0%). These findings show that SeV could prove to be a promising vector for efficient gene transfer to CB HSCs, while preserving their ability to reconstitute the entire hematopoietic series.
| Original language | English |
|---|---|
| Pages (from-to) | 272-277 |
| Number of pages | 6 |
| Journal | Gene Therapy |
| Volume | 10 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - Feb 1 2003 |
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All Science Journal Classification (ASJC) codes
- Molecular Medicine
- Molecular Biology
- Genetics
Cite this
Recombinant Sendai virus provides a highly efficient gene transfer into human cord blood-derived hematopoietic stem cells. / Jin, C. H.; Kusuhara, K.; Yonemitsu, Y.; Nomura, A.; Okano, S.; Takeshita, H.; Hasegawa, M.; Sueishi, K.; Hara, T.
In: Gene Therapy, Vol. 10, No. 3, 01.02.2003, p. 272-277.Research output: Contribution to journal › Review article
}
TY - JOUR
T1 - Recombinant Sendai virus provides a highly efficient gene transfer into human cord blood-derived hematopoietic stem cells
AU - Jin, C. H.
AU - Kusuhara, K.
AU - Yonemitsu, Y.
AU - Nomura, A.
AU - Okano, S.
AU - Takeshita, H.
AU - Hasegawa, M.
AU - Sueishi, K.
AU - Hara, T.
PY - 2003/2/1
Y1 - 2003/2/1
N2 - Hematopoietic stem cells (HSCs) are a promising target for gene therapy, however, the low efficiencies of gene transfer using currently available vectors face practical limitations. We have recently developed a novel and efficient gene transfer agent, namely recombinant Sendai virus (SeV), and we have here characterized SeV-mediated gene transfer to human cord blood (CB) HSCs and primitive progenitor cells (PPC) using the jelly fish green fluorescent protein (GFP) gene. Even at a relatively low titer (10 multiplicity of infections), SeV achieved highly efficient GFP expression in CB CD34+ cells (85.5 ± 5.8%), as well as more immature CB progenitor cells, CD34+AC133+ (88.2 ± 3.7%) and CD34+CD38- (84.6 ± 5.7%) cells, without cytokines prestimulation, that was a clear contrast to the features of gene transfer using retroviruses. SeV-mediated gene transfer was not seriously affected by the cell cycle status. In vitro cell differentiation studies revealed that gene transfer occurred in progenitor cells of all lineages (GM-CFU, 73.0 ± 11.1%; BFU-E, 24.7 ± 4.0%; Mix-CFU, 59 ± 4.0%; and total, 50.0 ± 7.0%). These findings show that SeV could prove to be a promising vector for efficient gene transfer to CB HSCs, while preserving their ability to reconstitute the entire hematopoietic series.
AB - Hematopoietic stem cells (HSCs) are a promising target for gene therapy, however, the low efficiencies of gene transfer using currently available vectors face practical limitations. We have recently developed a novel and efficient gene transfer agent, namely recombinant Sendai virus (SeV), and we have here characterized SeV-mediated gene transfer to human cord blood (CB) HSCs and primitive progenitor cells (PPC) using the jelly fish green fluorescent protein (GFP) gene. Even at a relatively low titer (10 multiplicity of infections), SeV achieved highly efficient GFP expression in CB CD34+ cells (85.5 ± 5.8%), as well as more immature CB progenitor cells, CD34+AC133+ (88.2 ± 3.7%) and CD34+CD38- (84.6 ± 5.7%) cells, without cytokines prestimulation, that was a clear contrast to the features of gene transfer using retroviruses. SeV-mediated gene transfer was not seriously affected by the cell cycle status. In vitro cell differentiation studies revealed that gene transfer occurred in progenitor cells of all lineages (GM-CFU, 73.0 ± 11.1%; BFU-E, 24.7 ± 4.0%; Mix-CFU, 59 ± 4.0%; and total, 50.0 ± 7.0%). These findings show that SeV could prove to be a promising vector for efficient gene transfer to CB HSCs, while preserving their ability to reconstitute the entire hematopoietic series.
UR - http://www.scopus.com/inward/record.url?scp=0037320759&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037320759&partnerID=8YFLogxK
U2 - 10.1038/sj.gt.3301877
DO - 10.1038/sj.gt.3301877
M3 - Review article
C2 - 12571635
AN - SCOPUS:0037320759
VL - 10
SP - 272
EP - 277
JO - Gene Therapy
JF - Gene Therapy
SN - 0969-7128
IS - 3
ER -