Effective repeat administration with adenovirus vectors to the muscle.
Effective repeat administration of adenovirus vectors following intranasal or intravenous delivery is hindered by a strong neutralizing antibody response to the vector. Intramuscular administration of adenovirus vectors elicited a neutralizing antibody response that peaked between 14 and 21 days after infection. However, effective repeat intramuscular administration of adenovirus vectors was not hindered by the presence of neutralizing antibodies in the serum. Surprisingly, beta-galactosidase expression in the skeletal muscle of immunized mice was equivalent to that observed in control mice. As expected, these serum neutralizing antibodies effectively blocked repeat administration of adenovirus vectors when delivered via the intravenous route. These results were observed in both C57BL/6 and Balb/c mice and thus do not appear to be strain specific. Successful repeat administration of adenovirus vectors to skeletal muscle has significant implications for the use of adenovirus vectors clinically and for increasing the safety and efficacy of adenovirus vector gene delivery.
Chen
P
P
GenVec, Inc., Gaithersburg, MD 20878, USA.
Kovesdi
I
I
Bruder
J T
JT
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D000906:Antibodies / Q000097:blood; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage* / Q000276:immunology; D007273:Injections, Intramuscular; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D001616:beta-Galactosidase / Q000235:genetics
D000906:Antibodies; D001616:beta-Galactosidase