Transduction of CD34+ enriched cord blood and Gaucher bone marrow cells by a retroviral vector carrying the glucocerebrosidase gene

Gene Ther. 1994 May;1(3):176-84.

Abstract

One promising strategy for gene therapy of Gaucher disease involves ex vivo retroviral transduction of autologous hematopoietic stem cells. Studies in small animals have demonstrated that this approach provides a life-long supply of the glucocerebrosidase (GC) enzyme. Human application has developed to the stage of a clinical trial. In this study, we describe development of a high titer amphotropic producer line for the vector, MFG-GC, and explore transduction of CD34+ cells from various human sources. Higher than three times the normal levels of glucocerebrosidase activity in non-transduced cells were achieved following transduction of CD34+ cells obtained from bone marrow or cord blood from normal donors. The improvement in enzyme activity in Gaucher marrow was about 40-fold above deficient levels. We examined the timing and stepwise effect of multiple rounds of infection and evaluated post-infection expansion of cells in two different cytokine mixtures. Transduction efficiency was determined using immunocytochemistry and Southern blot hybridization.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antigens, CD34 / metabolism
  • Bone Marrow / enzymology
  • Bone Marrow / pathology
  • Fetal Blood / cytology
  • Fetal Blood / enzymology*
  • Fetal Blood / immunology
  • Gaucher Disease / enzymology
  • Gaucher Disease / pathology
  • Gaucher Disease / therapy*
  • Genetic Therapy
  • Genetic Vectors*
  • Glucosylceramidase / genetics*
  • Humans
  • In Vitro Techniques
  • Infant, Newborn
  • Retroviridae / genetics*
  • Transduction, Genetic*

Substances

  • Antigens, CD34
  • Glucosylceramidase