Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: DrugBank:EXPT01586 (
G418
)
2,237
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Apolipoprotein A-I (apo A-I) and
lecithin-cholesterol acyltransferase
(
LCAT
) are constituents of circulating high-density lipoprotein (HDL) particles and play an important role in 'reverse cholesterol transport', the process by which cholesterol in peripheral tissues is transferred to the liver for excretion. Enhancing levels of apo A-I, as well as
LCAT
, in plasma may promote the removal of excess cholesterol from the arterial wall and thus reduce the formation of atherosclerotic lesions. Indeed, both apo A-I and
LCAT
genes have been identified as therapeutic targets to prevent or limit atherogenesis. Here, we have constructed two retroviral vectors, one containing
LCAT
cDNA and the neomycin phosphotransferase (NEO) gene (pLLEN), the other apo A-I cDNA,
LCAT
cDNA and the NEO gene (pLAPLEN) linked by internal ribosome entry sites (IRES). Both bi- and tricistronic retroviral vectors efficiently co-expressed their two or three genes when transfected into cultured mouse C2C12 muscle cells or human 293 cells. After 30 days, the retroviral vector sequences were retained by the host cells, whereas those of a conventional plasmid vector were lost. Moreover, transduced C2C12 mouse myoblasts maintained the ability for heterologous expression of human
LCAT
and apo A-I even after differentiation into myotubes. Stably-transduced clones of C2C12 cells were selected by neomycin (
G418
) resistance and continued to efficiently express human
LCAT
for 60 days. These findings indicate that the use of polycistronic retrovirus vectors to genetically modify myoblasts, which can be transplanted back into skeletal muscle, might be a safe and feasible strategy to express human apo A-I and
LCAT
and hence have therapeutic potential to regress atherosclerotic lesions.
...
PMID:Construction and characterization of polycistronic retrovirus vectors for sustained and high-level co-expression of apolipoprotein A-I and lecithin-cholesterol acyltransferase. 1052 35
