Recombinant Sendai virus provides a highly efficient gene transfer into human cord blood-derived hematopoietic stem cells

Gene Ther. 2003 Feb;10(3):272-7. doi: 10.1038/sj.gt.3301877.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Colony-Forming Units Assay
  • Cord Blood Stem Cell Transplantation
  • Fetal Blood / cytology*
  • Gene Expression
  • Genetic Therapy / methods*
  • Genetic Vectors / administration & dosage*
  • Genetic Vectors / genetics
  • Green Fluorescent Proteins
  • Hematopoietic Stem Cells / metabolism*
  • Humans
  • Luminescent Proteins / genetics
  • Sendai virus / genetics*
  • T-Lymphocytes / metabolism
  • Transduction, Genetic / methods*

Substances

  • Luminescent Proteins
  • Green Fluorescent Proteins