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

Molecular Therapy : the Journal of the American Society of Gene Therapy
Lingfei XuKatherine Parker Ponder

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 x 10(10) transducing units/kg of RV, peripheral blood cells had approximately 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 ...Continue Reading

References

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Citations

Jun 14, 2014·Molecular Therapy : the Journal of the American Society of Gene Therapy·Denise Carbonaro SarracinoDonald B Kohn
Jun 10, 2011·Virology Journal·Daniel Cervantes-GarciaDavid Camerini
Sep 23, 2006·Expert Opinion on Biological Therapy·Shu Uin GanRoy Y Calne
Jul 14, 2010·Advanced Drug Delivery Reviews·Qizhen Shi, Robert R Montgomery
Aug 19, 2007·Biomaterials·Charles A GersbachAndrés J García
Feb 3, 2007·Journal of Thrombosis and Haemostasis : JTH·Q ShiR R Montgomery
Sep 6, 2005·Molecular Therapy : the Journal of the American Society of Gene Therapy·Tuan Huy NguyenNicolas Ferry
Dec 9, 2004·Molecular Therapy : the Journal of the American Society of Gene Therapy·Yuli LiuKatherine Parker Ponder
Sep 12, 2008·Journal of Computational Chemistry·T R Walsh, T Liang
Nov 23, 2006·Journal of Structural and Functional Genomics·Kenneth LundstromFranc Pattus

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