Blood, Vol. 95 No. 3 (February 1), 2000:
pp. 829-836
Long-term multilineage expression in peripheral blood from a
Moloney murine leukemia virus vector after serial transplantation of
transduced bone marrow cells
Timothy W. Austin,
Suzan Salimi,
Gabor Veres,
Franck Morel,
Heini Ilves,
Roland Scollay, and
Ivan Plavec
From SyStemix Inc, Palo Alto, CA.
Using a mouse bone marrow transplantation model, the authors
evaluated a Moloney murine leukemia virus (MMLV)-based vector encoding 2 anti-human immunodeficiency virus genes for long-term expression in blood cells. The vector also encoded the human nerve growth factor receptor (NGFR) to serve as a cell-surface marker for in
vivo tracking of transduced cells. NGFR+ cells were
detected in blood leukocytes of all mice (n=16; range 16%-45%) 4 to 5 weeks after transplantation and were repeatedly detected in blood
erythrocytes, platelets, monocytes, granulocytes, T cells, and B cells
of all mice for up to 8 months. Transgene expression in individual mice
was not blocked in the various cell lineages of the peripheral blood
and spleen, in several stages of T-cell maturation in the thymus, or in
the Lin
/loSca-1+ and
c-kit+Sca-1+ subsets of bone
marrow cells highly enriched for long-term
multilineage-reconstituting activity. Serial transplantation of
purified NGFR+c-kit+Sca-1+
bone marrow cells resulted in the reconstitution of multilineage hematopoiesis by donor type NGFR+ cells in all engrafted
mice. The authors concluded that MMLV-based vectors were capable of
efficient and sustained transgene expression in multiple lineages of
peripheral blood cells and hematopoietic organs and in hematopoietic
stem cell (HSC) populations. Differentiation of engrafting HSC to
peripheral blood cells is not necessarily associated with dramatic
suppression of retroviral gene expression. In light of earlier studies
showing that vector elements other than the long-terminal repeat
enhancer, promoter, and primer binding site can have an impact on
long-term transgene expression, these findings accentuate the
importance of empirically testing retroviral vectors to determine
lasting in vivo expression.
