Adeno-associated virus type 2-mediated transduction of murine hematopoietic cells with long-term repopulating ability and sustained expression of a human globin gene in vivo

Selvarangan Ponnazhagan, Mervin C. Yoder, Arun Srivastava

Research output: Contribution to journalArticle

65 Citations (Scopus)

Abstract

Adeno-associated virus type 2 (AAV), a nonpathogenic human parvovirus, is gaining attention as a vector for potential use in human gene therapy. We and others have described AAV-mediated β-globin gene transfer and expression in established human and murine erythroleukemia cell lines in vitro. However, successful AAV-mediated globin gene transduction of hematopoietic stem cells and long-term expression in vivo in progeny cells have not been documented. We report here that infection of murine hematopoietic bone marrow cells ex vivo with a recombinant AAV vector containing the genomic copy of a normal human globin gene followed by transplantation of these cells into lethally irradiated congenic mice resulted in efficient gene transfer into hematopoietic cells with long-term repopulating ability as detected by the presence of the human globin gene sequences in bone marrow and spleen in primary recipient mice for at least 6 months. Long-term expression of the human globin gene was also detected in bone marrow, but not in spleen, in primary recipient mice. Furthermore, in secondary-transplant experiments, we were also able to document the presence as well as expression of the transduced human globin gene in mouse bone marrow for up to 3 months. These results provide further support for potential use of the AAV-based vector system in gene therapy of human hemoglobinopathies in general and sickle- cell anemia and β-thalassemia in particular.

Original languageEnglish (US)
Pages (from-to)3098-3104
Number of pages7
JournalJournal of virology
Volume71
Issue number4
StatePublished - Apr 1 1997

Fingerprint

Dependovirus
Globins
mice
Genes
genes
cells
bone marrow
gene therapy
Bone Marrow
gene transfer
Genetic Therapy
spleen
Spleen
thalassemia
Congenic Mice
sickle cell anemia
Hemoglobinopathies
Parvovirus
Leukemia, Erythroblastic, Acute
cell transplantation

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Adeno-associated virus type 2-mediated transduction of murine hematopoietic cells with long-term repopulating ability and sustained expression of a human globin gene in vivo. / Ponnazhagan, Selvarangan; Yoder, Mervin C.; Srivastava, Arun.

In: Journal of virology, Vol. 71, No. 4, 01.04.1997, p. 3098-3104.

Research output: Contribution to journalArticle

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