Toward gene therapy of endometriosis: transductional and transcriptional targeting of adenoviral vectors to endometriosis cells

Othman, Essam-Eldin R.; Zhu, Zeng B.; Curiel, David T.; Khatoon, Nilufar; Salem, Hosam T.; Khalifa, Essam Al-Din M.; Al-Hendy, Ayman

doi:10.1016/j.ajog.2008.01.059

« Previous Next »American Journal of Obstetrics & Gynecology
Volume 199, Issue 2 , Pages 117.e1-117.e6, August 2008

Toward gene therapy of endometriosis: transductional and transcriptional targeting of adenoviral vectors to endometriosis cells

Presented at the 54th Annual Scientific Meeting of the Society for Gynecologic Investigation, Reno, NV, March 14-17, 2007.

Essam-Eldin R. Othman, MD
- Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, TX
- Department of Obstetrics and Gynecology, Assiut University, Assiut City, Egypt
Zeng B. Zhu, MD
- Gene Therapy Center, University of Alabama at Birmingham, Birmingham, AL
David T. Curiel, MD, PhD
- Gene Therapy Center, University of Alabama at Birmingham, Birmingham, AL
Nilufar Khatoon, MSc
- Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, TX
Hosam T. Salem, MD, PhD
- Department of Obstetrics and Gynecology, Assiut University, Assiut City, Egypt
Essam Al-Din M. Khalifa, MD
- Department of Obstetrics and Gynecology, Assiut University, Assiut City, Egypt
Ayman Al-Hendy, MD, PhD
- Department of Obstetrics and Gynecology, Center for Women's Health Research, Meharry Medical School, Nashville, TN.
- Reprint requests: Ayman Al-Hendy, MD, PhD, Department of Obstetrics and Gynecology, Center for Women Health Research, Meharry Medical College, 1005 Dr D.B. Todd Jr Blvd, Nashville, TN 37208

Received 30 July 2007; accepted 29 January 2008.

Objective

The purpose of this study was to screen a panel of targeted adenoviruses as vectors for endometriosis gene therapy.

Study Design

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.

Conclusion

Ad-heparanase-luc showed “endometriosis on, liver off” phenotype and is a promising vector for endometriosis gene therapy.

Key words: adenovirus, endometriosis, gene therapy, targeting strategy

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Cite this article as: Othman ER, Zhu ZB, Curiel DT, et al. Toward gene therapy of endometriosis: transductional and transcriptional targeting of adenoviral vectors to endometriosis cells. Am J Obstet Gynecol 2008;199:117.e1-117.e6.

Supported by Grants DOD W81XWH-05-1-0035 and NIH R01CA083821 (D.T.C.); G12 RR03032 from the National Center for Research Resources, NIH (A.A.); and a grant from the Egyptian Mission Department (E.R.O.).

PII: S0002-9378(08)00131-2

doi:10.1016/j.ajog.2008.01.059

Refers to article:

Memy I: a novel murine model for uterine leiomyoma using adenovirus-enhanced human fibroid explants in severe combined immune deficiency mice , 12 May 2008
Memy H. Hassan, Eduardo Eyzaguirre, Hossam M.M. Arafa, Farid M.A. Hamada, Salama A. Salama, Ayman Al-Hendy
American Journal of Obstetrics & Gynecology August 2008 (Vol. 199, Issue 2, Pages 156.e1-156.e8)