PMID- 16972763
OWN - NLM
STAT- MEDLINE
DCOM- 20061101
LR  - 20220330
IS  - 1043-0342 (Print)
IS  - 1043-0342 (Linking)
VI  - 17
IP  - 9
DP  - 2006 Sep
TI  - Development of a synthetic promoter for macrophage gene therapy.
PG  - 949-59
AB  - Macrophages have the potential to deliver therapeutic genes to many target 
      tissues. Macrophage-specific synthetic promoters (SPs) generated by random 
      ligation of myeloid/macrophage cis elements had activity up to 100-fold that of a 
      native macrophage promoter in macrophage cell lines, but were minimally active in 
      nonmyeloid cells. Mouse bone marrow cells (BMCs) transduced ex vivo with 
      lentivectors expressing green fluorescent protein (GFP) driven either by an SP 
      (SP-GFP) or a cytomegalovirus (CMV) promoter (CMV-GFP) were used for syngeneic 
      transplantation of lethally irradiated mice. Blood leukocytes showed stable GFP 
      expression for up to 15 months after transplantation. SP-GFP expression was 
      selective for CD11b+ macrophages, whereas CMV-GFP expression was observed in 
      erythrocytes, as well as in both CD11b+ and CD11b- leukocytes. Furthermore, 
      SP-GFP expression was much stronger than CMV-GFP expression in CD11b+ 
      macrophages. apoE-/- BMCs transduced with the lentiviral vector encoding human 
      apoE were used to transplant apoE-/- mice. Macrophage expression of apoE from 10 
      to 26 weeks of age significantly reduced atherosclerotic lesions in recipient 
      apoE-/- mice. Thus, the novel SPs, especially when combined with lentivectors, 
      are useful for macrophage-specific delivery of therapeutic genes.
FAU - He, Weijing
AU  - He W
AD  - Department of Medicine, University of Texas Health Science Center at San Antonio, 
      and South Texas Veterans Health Care System, Audie L. Murphy Division, San 
      Antonio, TX 78229-3900, USA.
FAU - Qiang, Mei
AU  - Qiang M
FAU - Ma, Wuqiong
AU  - Ma W
FAU - Valente, Anthony J
AU  - Valente AJ
FAU - Quinones, Marlon P
AU  - Quinones MP
FAU - Wang, Wen
AU  - Wang W
FAU - Reddick, Robert L
AU  - Reddick RL
FAU - Xiao, Qifu
AU  - Xiao Q
FAU - Ahuja, Seema S
AU  - Ahuja SS
FAU - Clark, Robert A
AU  - Clark RA
FAU - Freeman, Gregory L
AU  - Freeman GL
FAU - Li, Senlin
AU  - Li S
LA  - eng
GR  - R01 AG019519/AG/NIA NIH HHS/United States
GR  - R01 AI020866/AI/NIAID NIH HHS/United States
GR  - AI20866/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Hum Gene Ther
JT  - Human gene therapy
JID - 9008950
RN  - 0 (Apolipoproteins E)
RN  - 0 (DNA Primers)
SB  - IM
MH  - Animals
MH  - Apolipoproteins E/biosynthesis/genetics
MH  - Atherosclerosis/therapy
MH  - Base Sequence
MH  - Blotting, Western
MH  - Bone Marrow/metabolism
MH  - Cell Line
MH  - DNA Primers
MH  - Female
MH  - Flow Cytometry
MH  - *Genetic Therapy
MH  - Genetic Vectors
MH  - Humans
MH  - Lentivirus/genetics
MH  - Macrophages, Peritoneal/*cytology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - *Promoter Regions, Genetic
EDAT- 2006/09/16 09:00
MHDA- 2006/11/02 09:00
CRDT- 2006/09/16 09:00
PHST- 2006/09/16 09:00 [pubmed]
PHST- 2006/11/02 09:00 [medline]
PHST- 2006/09/16 09:00 [entrez]
AID - 10.1089/hum.2006.17.949 [doi]
PST - ppublish
SO  - Hum Gene Ther. 2006 Sep;17(9):949-59. doi: 10.1089/hum.2006.17.949.