|
|
Prepublished online as a Blood First Edition Paper on September 5, 2002; DOI 10.1182/blood-2002-07-2131.
 Previous Article | Table of Contents | Next Article 
Blood, 15 January 2003, Vol. 101, No. 2, pp. 485-491
GENE THERAPY
Gene therapy of apolipoprotein E-deficient mice using a novel
macrophage-specific retroviral vector
Peter J. Gough and
Elaine W. Raines
From the Department of Pathology, University of
Washington, Seattle.
The use of retroviral gene transfer into hematopoietic stem cells
for human gene therapy has been hampered by the absence of retroviral
vectors that can generate long-lasting, lineage-specific gene
expression. We developed self-inactivating retroviral vectors that
incorporate gene-regulatory elements from the macrophage-restricted human CD68 gene. Through the transplantation of transduced
murine hematopoietic stem cells (HSCs), we show that a vector
incorporating a 342-base pair (bp) fragment of 5' flanking sequence
from the CD68 gene, in addition to the CD68 first intron,
was able to direct macrophage-specific expression of an enhanced green
fluorescent protein (EGFP) reporter gene in inflammatory cell
exudates and lymphoid organs in vivo. Levels of EGFP expression
generated by this vector were greater than those generated by a
standard Moloney murine leukemia retroviral vector, and they were
stable for at least a year after transplantation of transduced HSCs. To
evaluate the ability of this vector to generate therapeutically useful levels of gene expression, we transplanted apolipoprotein E
(ApoE)-deficient HSCs transduced with a virus encoding ApoE into
ApoE-deficient mice. Macrophages from these mice expressed levels of
ApoE that were comparable to those from wild-type mice, and
vector-driven expression of ApoE in macrophages was sufficient to
reverse both hypercholesterolemia and atherosclerotic lesion
development. The future application of this retroviral vector should
provide a powerful tool to further elucidate macrophage function and
for human gene therapy.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
Y. R. Su, J. L. Blakemore, Y. Zhang, M. F. Linton, and S. Fazio
Lentiviral Transduction of ApoAI Into Hematopoietic Progenitor Cells and Macrophages: Applications to Cell Therapy of Atherosclerosis
Arterioscler Thromb Vasc Biol,
August 1, 2008;
28(8):
1439 - 1446.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. E. Wisse, K. Ogimoto, J. Tang, M. K. Harris Jr., E. W. Raines, and M. W. Schwartz
Evidence that Lipopolysaccharide-Induced Anorexia Depends upon Central, Rather than Peripheral, Inflammatory Signals
Endocrinology,
November 1, 2007;
148(11):
5230 - 5237.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Scatena, L. Liaw, and C. M. Giachelli
Osteopontin: A Multifunctional Molecule Regulating Chronic Inflammation and Vascular Disease
Arterioscler Thromb Vasc Biol,
November 1, 2007;
27(11):
2302 - 2309.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. M. Schwartz, Z. S. Galis, M. E. Rosenfeld, and E. Falk
Plaque Rupture in Humans and Mice
Arterioscler Thromb Vasc Biol,
April 1, 2007;
27(4):
705 - 713.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. A. Bostrom, B. B. Boyanovsky, C. T. Jordan, M. P. Wadsworth, D. J. Taatjes, F. C. de Beer, and N. R. Webb
Group V Secretory Phospholipase A2 Promotes Atherosclerosis: Evidence From Genetically Altered Mice
Arterioscler Thromb Vasc Biol,
March 1, 2007;
27(3):
600 - 606.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. S. Meir and E. Leitersdorf
Atherosclerosis in the Apolipoprotein E-Deficient Mouse: A Decade of Progress
Arterioscler Thromb Vasc Biol,
June 1, 2004;
24(6):
1006 - 1014.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. J. Gough, K. J. Garton, P. T. Wille, M. Rychlewski, P. J. Dempsey, and E. W. Raines
A Disintegrin and Metalloproteinase 10-Mediated Cleavage and Shedding Regulates the Cell Surface Expression of CXC Chemokine Ligand 16
J. Immunol.,
March 15, 2004;
172(6):
3678 - 3685.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
