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Blood, 1 August 2001, Vol. 98, No. 3, pp. 604-609
GENE THERAPY
Gene transfer into murine hematopoietic stem cells with
helper-free foamy virus vectors
George Vassilopoulos,
Grant Trobridge,
Neil C. Josephson, and
David W. Russell
From the Division of Hematology, University of
Washington, Seattle, WA.
Gene transfer into hematopoietic stem cells (HSCs) is an ideal
treatment strategy for many genetic and hematologic diseases. However,
progress has been limited by the low HSC transduction rates obtained
with retroviral vectors based on murine leukemia viruses. This study
examined the potential of vectors derived from the nonpathogenic human
foamy virus (HFV) to transduce human CD34+ cells and murine
HSCs. More than 80% of human hematopoietic progenitors present in
CD34+ cell preparations derived from cord blood were
transduced by a single overnight exposure to HFV vector stocks. Mice
that received transduced bone marrow cells expressed the vector-encoded
transgene long term in all major hematopoietic cell lineages and in
over 50% of cells in some animals. Secondary bone marrow transplants and integration site analysis confirmed that gene transfer occurred at
the stem cell level. Transgene silencing was not observed. Thus vectors
based on foamy viruses represent a promising approach for HSC gene therapy.
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