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.
N1 - Funding Information:
We thank Dr Kusuo Sanada for providing cord blood samples. This study was supported by a Grant of Promotion of Basic Scientific Research in Medical Frontier of the Organization for Pharmaceutical Safety and Research, and by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan. M Ohara provided language assistance.
PY - 2003/2
Y1 - 2003/2
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.
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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 -