In vivo transduction of hematopoietic stem cells after neonatal intravenous injection of an amphotropic retroviral vector in mice

Lingfei Xu, Tom O'Malley, Mark S. Sands, Bin Wang, Todd Meyerrose, Mark E. Haskins, Katherine Parker Ponder

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Hematopoietic stem cells (HSC) are important targets for gene therapy. Most protocols involve ex vivo modification, in which HSC are transduced in vitro and injected into the recipient. An in vivo delivery method might simplify HSC gene therapy. We previously demonstrated that iv injection of an amphotropic retroviral vector (RV) into newborn mice resulted in long-term expression from hepatocytes. The goal of this study was to determine if HSC were also transduced. After neonatal administration of 1 × 1010 transducing units/kg of RV, peripheral blood cells had ∼0.1 copy of RV per cell for up to 22 months. At 18 months, RV sequences were detected in T, B, and myeloid cells from bone marrow (BM). Unfractionated BM was transplanted into naive recipients after total body irradiation. Recipients maintained similar levels of the RV in their blood cells for 10 months, at which time RV sequences were present at the same integration site in all lineages of cells from BM. We conclude that neonatal iv injection of RV results in transduction of HSC in mice, which might be used for BM-directed gene therapy. Transduction of blood cells after liver-directed neonatal gene therapy might have adverse effects in patients, although no leukemias developed here.

Original languageEnglish
Pages (from-to)37-44
Number of pages8
JournalMolecular Therapy
Volume10
Issue number1
DOIs
StatePublished - Jul 2004

Keywords

  • Amphotropic
  • Clonal marking
  • Hematopoietic stem cell
  • LAM-PCR
  • Neonatal gene therapy
  • Retroviral vector

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