Polyethylene glycol (molecular weight 400 DA) vehicle improves gene expression of adenovirus mediated gene therapy.
OBJECTIVE
A significant limitation of adenoviral mediated suicide gene therapy is poor gene distribution in vivo. The choice of vehicle has been demonstrated to affect the level of adenoviral delivered gene transduction. We examined the hypotheses that 1) adenovirus suspended in PEG400 improves gene expression in the naïve canine prostate model, 2) improved transgene expression with PEG400 results in improved tumor control and 3) vehicle affects the initial adenoviral spread from a single intratumor injection.


METHODS
The magnitude and volume of gene expression were measured 24 hours following intraprostatic injection of adenovirus suspended in PEG400 (12.5% weight per volume) or saline as vehicle. Tumor growth delay was measured in mice bearing human tumor xenografts following the injection of adenovirus in PEG400 and saline. The initial spread of adenovirus was measured by confocal microscopy following a single injection of fluorescently labeled adenoviral particles in human tumor xenografts using each vehicle.


RESULTS
Adenovirus suspended in PEG400 provided an average of twice the level of gene expression in the canine prostate and significantly better tumor control relative to saline in preclinical tumor models (p = 0.046 and 0.036, respectively). The initial spread of adenovirus with PEG400 was superior to that of adenovirus in saline and the latter was largely limited to the needle tract.


CONCLUSIONS
Adenoviral gene therapy vectors suspended in PEG400 results in improved tumor control because of greater initial adenoviral spread, and the increased volume and magnitude of gene expression in vivo.
Barton
K N
KN
Department of Radiation Oncology, Henry Ford Health System, Detroit, Michigan 48202, USA.
Stricker
H
H
Kolozsvary
A
A
Kohl
R
R
Heisey
G
G
Nagaraja
T N
TN
Zhu
G
G
Lu
M
M
Kim
J H
JH
Freytag
S O
SO
Brown
S L
SL
D000256:Adenoviridae / Q000235:genetics*; D004337:Drug Carriers; D015967:Gene Expression Regulation, Viral; D015316:Genetic Therapy / Q000379:methods*; D011092:Polyethylene Glycols
D004337:Drug Carriers; D011092:Polyethylene Glycols