Safety and efficacy of adenovirus-mediated transfer of the human aquaporin-1 cDNA to irradiated parotid glands of non-human primates.
This study evaluated the safety and efficacy of a single administration of a recombinant adenovirus encoding human aquaporin-1 (AdhAQP1) to the parotid glands of adult rhesus monkeys. In anticipation of possible clinical use of this virus to correct irradiation damage to salivary glands, AdhAQP1 was administered (at either 2 x 10(9) or 1 x 10(8) plaque-forming units/gland) intraductally to irradiated glands and to their contralateral nonirradiated glands. Radiation (single dose, 10 Gy) significantly reduced salivary flow in exposed glands. Virus administration resulted in gene transfer to irradiated and nonirradiated glands and was without untoward local (salivary) or systemic (sera chemistry, complete blood count) effects in all animals. However, the effect of AdhAQP1 administration varied and did not result in a consistent positive effect on salivary flow rates for all animals under these experimental conditions. We conclude that a single adenoviral-mediated gene transfer to primate salivary glands is well-tolerated, although its functional utility in enhancing fluid secretion from irradiated parotid glands is inconsistent.
O'Connell
A C
AC
Gene Therapy and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892, USA.
Baccaglini
L
L
Fox
P C
PC
O'Connell
B C
BC
Kenshalo
D
D
Oweisy
H
H
Hoque
A T
AT
Sun
D
D
Herscher
L L
LL
Braddon
V R
VR
Delporte
C
C
Baum
B J
BJ
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D051398:Aquaporin 1; D020346:Aquaporins / Q000235:genetics*; D001789:Blood Group Antigens; D018076:DNA, Complementary; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006801:Humans; D007259:Infrared Rays; D008253:Macaca mulatta; D008297:Male; D010306:Parotid Gland / Q000378:metabolism* / Q000528:radiation effects; D011995:Recombination, Genetic
C496020:AQP1 protein, human; D020346:Aquaporins; D001789:Blood Group Antigens; D018076:DNA, Complementary; D051398:Aquaporin 1