Transgene expression in the rhesus cervix mediated by an adenovirus expressing beta-galactosidase.
OBJECTIVE
More than 90% of cervical cancers are positive for human papillomavirus, which functionally represses p53 and pRb. The remainder have been found to contain p53 mutations. Gene therapy involves insertion of a functioning gene into a patient to correct a genetic abnormality.


METHODS
The ability of a beta-galactosidase adenovirus to mediate transgene expression in the rhesus cervix was evaluated. Three different doses and two different entry techniques of virus were investigated.


RESULTS
The ideal dose determined by X-galactosidase staining was 2 x 10(10) plaque-forming units, and the injection method yielded better staining than did abrasion with topical application. Increased adenoviral-specific immunoglobulin G antibody response in the injected monkeys confirmed the results.


CONCLUSIONS
High transduction efficiency by use of adenoviral vectors can be achieved in the cervix. Reversing the effects of human papillomavirus and p53 mutations with gene therapy may become a novel therapy for invasive and preinvasive cervical cancer.
Mitchell
M F
MF
Department of Gynecologic Oncology, University of Texas M.D. Anderson Cancer Center, Houston, 77030, USA.
Hamada
K
K
Sastry
K J
KJ
Sarkar
A
A
Tortolero-Luna
G
G
Wharton
J T
JT
Roth
J A
JA
D000256:Adenoviridae / Q000235:genetics* / Q000276:immunology; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D002584:Cervix Uteri / Q000201:enzymology*; D005260:Female; D015870:Gene Expression; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D007070:Immunoglobulin A / Q000097:blood; D008253:Macaca mulatta; D001616:beta-Galactosidase / Q000032:analysis / Q000235:genetics*
D000914:Antibodies, Viral; D007070:Immunoglobulin A; D001616:beta-Galactosidase