Gene transfer to mouse heart and skeletal muscles using a minicircle expressing human vascular endothelial growth factor.
BACKGROUND
: Gene transfer to heart muscle is a promising modality to treat ischemic heart disease. However, current vectors are inefficient and need to be improved. A novel vector system that shows great promise is the minicircle (MC) vector being smaller than conventional plasmid vectors and devoid of bacterial sequences.


OBJECTIVE
: To study gene transfer of MC DNA, expressing the human vascular endothelial growth factor (hVEGF), to mouse heart and skeletal muscles and to compare it with one of the efficient plasmids used in cardiovascular trials, the phVEGF165 containing the same expression cassette as the MC.


RESULTS
: The MC and the phVEGF165 plasmid show similar expression patterns both in vitro and in mouse heart and skeletal muscle studies in vivo on molar basis (equal expression in heart 24 hours, 0.9 fold lower expression from MC in heart and 1.9 fold higher in skeletal muscle at 7 days), whereas on weight basis the MC construct was more efficient in skeletal muscle (5.6 fold higher expression, P < 0.05), and at least as efficient in heart (1.6 fold higher expression).


CONCLUSIONS
: The gene expression is similar in the 2 vector systems, so the smaller size and the fact that the MC construct is devoid of bacterial sequences and antibiotics resistance gene make the MC vector an attractive alternative for nonviral gene therapy.
Stenler
Sofia
S
Vecura, Clinical Research Center, Karolinska University Hospital Huddinge, Stockholm, Sweden.
Andersson
Agneta
A
Simonson
Oscar E
OE
Lundin
Karin E
KE
Chen
Zhi-Ying
ZY
Kay
Mark A
MA
Smith
C I Edvard
CI
Sylvén
Christer
C
Blomberg
Pontus
P
D000818:Animals; D001483:Base Sequence; D004247:DNA / Q000378:metabolism; D015870:Gene Expression; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism; D010957:Plasmids; D042461:Vascular Endothelial Growth Factor A
C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D004247:DNA