Regulated high-level human beta-globin gene expression in erythroid cells following recombinant adeno-associated virus-mediated gene transfer

Gene Ther. 1995 Jul;2(5):336-43.

Abstract

Gene therapy approaches for beta-thalassemia and sickle cell anemia focus on the transfer of a human beta-globin gene into the patient's hematopoietic stem cells (HSC). Expression of the transferred sequences should be erythroid specific and match the expression of the endogenous alpha-globin genes in adult erythropoiesis. Here we explore the potential of recombinant adeno-associated virus (AAV) vectors for human beta-globin gene transfer. We have constructed a recombinant AAV-vector containing a human beta-globin gene together with the DNasel hypersensitive sites 4, 3 and 2 of the human beta-globin locus control region. The vector replicates to high titers and can efficiently transduce hematopoietic and non-hematopoietic cells. In transduced and G418 selected murine erythroleukemia (MEL) cell clones, human beta-globin gene expression was regulated and reached levels comparable to endogenous murine beta maj. These data show that AAV-vectors are promising tools in gene therapy approaches for the haemoglobinopathies.

Publication types

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

MeSH terms

  • Animals
  • Cell Line, Transformed
  • Clone Cells
  • Cloning, Molecular
  • Dependovirus / genetics*
  • Erythroid Precursor Cells / metabolism*
  • Gene Expression Regulation, Viral*
  • Gene Transfer Techniques*
  • Globins / genetics*
  • Humans
  • Leukemia, Erythroblastic, Acute / genetics
  • Leukemia, Erythroblastic, Acute / pathology
  • Mice
  • Recombination, Genetic
  • Transduction, Genetic

Substances

  • Globins