1. Sustained high-level polyclonal hematopoietic marking and transgene expression 4 years after autologous transplantation of rhesus macaques with SIV lentiviral vector–transduced CD34+cells
- Author
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Kim, Yoo-Jin, Kim, Yoon-Sang, Larochelle, Andre, Renaud, Gabriel, Wolfsberg, Tyra G., Adler, Rima, Donahue, Robert E., Hematti, Peiman, Hong, Bum-Kee, Roayaei, Jean, Akagi, Keiko, Riberdy, Janice M., Nienhuis, Arthur W., Dunbar, Cynthia E., and Persons, Derek A.
- Abstract
We previously reported that lentiviral vectors derived from the simian immunodeficiency virus (SIV) were efficient at transducing rhesus hematopoietic repopulating cells. To evaluate the persistence of vector-containing and -expressing cells long term, and the safety implications of SIV lentiviral vector–mediated gene transfer, we followed 3 rhesus macaques for more than 4 years after transplantation with transduced CD34+cells. All 3 animals demonstrated significant vector marking and expression of the GFP transgene in T cells, B cells, and granulocytes, with mean GFP+levels of 6.7% (range, 3.3%-13.0%), 7.4% (4.2%-13.4%), and 5.6% (3.1%-10.5%), respectively. There was no vector silencing in hematopoietic cells over time. Vector insertion site analysis of granulocytes demonstrated sustained highly polyclonal reconstitution, with no evidence for progression to oligoclonality. A significant number of clones were found to contribute at both 1-year and 3- or 4-year time points. No vector integrations were detected in the MDS1/EVI1 region, in contrast to our previous findings with a γ-retroviral vector. These data show that lentiviral vectors can mediate stable and efficient long-term expression in the progeny of transduced hematopoietic stem cells, with an integration profile that may be safer than that of standard Moloney murine leukemia virus (MLV)–derived retroviral vectors.
- Published
- 2009
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