Most virally based vectors for gene therapy contain viral promoters that are tissue-nonspecific. Consequently, unintended expression of toxic therapeutic genes in normal tissues may potentially occur. We have constructed adenoviruses that contain a bacterial β-galactosidase (β-gal) gene (lacZ) under the control of three different prostate-specific promoters: prostate-specific antigen (PSA), probasin, and the mouse mammary-tumor-virus long terminal repeat (MMTV; prostate-specific Ad-lacZ). In general, these prostate-specific Ad-lacZ can effectively transduce and express β-gal in prostate cells and display weak, if any, expression of β-gal in nonprostate cells in vitro. In vivo, these adenoviruses showed a high level of β-gal expression in canine prostate but also disseminated to tissues other than prostate after intraprostatic (i.p.) injection. However, none of the prostate-specific Ad-lacZ expressed β-gal in these nonprostate tissues. Furthermore, prostate-specific Ad-lacZ expressed β-gal only in xenograft tumors grown in nude mice, derived from human prostate-cancer cells DU145 and PPC-1, but showed no β-gal expression in tumors derived from human bladder-cancer cells RT4. These results indicate that adenoviruses containing prostate-specific promoters may express intended transgenes specifically in prostate in vivo.
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Similar content being viewed by others Explore related subjectsDiscover the latest articles and news from researchers in related subjects, suggested using machine learning. Author information Authors and AffiliationsUniversity of Tennessee Urologic Research Laboratories, Department of Urology, College of Medicine, University of Tennessee, 956 Court Avenue, H220, Memphis, TN 38163, USA e-mail: ylu@utmem1.utmem.edu, Tel: +1-901-4485436, Fax: +1-901-4485496, , , , , , US
Yi Lu & Mitchell S. Steiner
Lu, Y., Steiner, M. Transcriptionally regulated adenoviruses for prostate-specific gene therapy. World J Urol 18, 93–101 (2000). https://doi.org/10.1007/s003450050180
Issue Date: April 2000
DOI: https://doi.org/10.1007/s003450050180
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