Toward gene therapy of endometriosis: transductional and transcriptional targeting of adenoviral vectors to endometriosis cells.
OBJECTIVE
The purpose of this study was to screen a panel of targeted adenoviruses as vectors for endometriosis gene therapy.


METHODS
Endometriotic cells were obtained from subjects with ovarian endometriomas. Liver tissues were taken from donors during hepatic transplantation surgery. Human endometriotic cells and liver tissues were transfected by targeted adenoviruses expressing luciferase reporter gene. Luciferase activity that was mediated by each virus was expressed as a percentage of adenovirus serotype 5 (Ad5-CMV-luc) activity. The 2-tailed Studentt test was used to compare the adenovirus data.


RESULTS
In endometriotic cells, the adenovirus-RGD (Ad-RGD-luc), adenovirus under secretory leukocyte protease inhibitor promoter (Ad-SLPI-luc), and adenovirus under heparanase promoter (Ad-heparanase-luc) showed significantly higher activity, compared with the adenovirus serotype 5. In liver tissues, adenovirus-survivin (Ad-survivin-luc) and Ad-heparanase-luc had significantly lower activity, compared with adenovirus serotype 5.


CONCLUSIONS
Ad-heparanase-luc showed "endometriosis on, liver off" phenotype and is a promising vector for endometriosis gene therapy.
Othman
Essam-Eldin R
EE
Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, TX, USA.
Zhu
Zeng B
ZB
Curiel
David T
DT
Khatoon
Nilufar
N
Salem
Hosam T
HT
Khalifa
Essam Al-Din M
EA
Al-Hendy
Ayman
A
D000256:Adenoviridae / Q000235:genetics*; D036022:Capsid Proteins; D002478:Cells, Cultured; D004715:Endometriosis / Q000628:therapy*; D004717:Endometrium / Q000166:cytology; D005260:Female; D018390:Gene Targeting / Q000379:methods*; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D005966:Glucuronidase / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000201:enzymology; D008156:Luciferases / Q000378:metabolism; D015533:Transcriptional Activation / Q000502:physiology; D014161:Transduction, Genetic / Q000379:methods; D014162:Transfection; D000099175:Heparanase
D036022:Capsid Proteins; D005966:Glucuronidase; D008156:Luciferases; D000099175:Heparanase