TRANSGENE EXPRESSION IN THE RHESUS CERVIX MEDIATED BY AN ADENOVIRUS EXPRESSING BETA-GALACTOSIDASE

OBJECTIVES: More than 90% of cervical cancers are positive for human p apillomavirus, which functionally represses p53 and pRb. The remainder have been found to contain p53 mutations. Gene therapy involves inser tion of a functioning gene into a patient to correct a genetic abnorma lity. STUDY DESIGN: 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 inve stigated. RESULTS: The ideal dose determined by X-galactosidase staini ng was 2 x 10(10) plaque-forming units, and the injection method yield ed better staining than did abrasion with topical application. Increas ed adenoviral-specific immunoglobulin G antibody response in the injec ted monkeys confirmed the results. CONCLUSION: High transduction effic iency by use of adenoviral vectors can be achieved in the cervix. Reve rsing the effects of human papillomavirus and p53 mutations with gene therapy may become a novel therapy for invasive and preinvasive cervic al cancer.