Highly specific transgene expression mediated by a complex adenovirus vector incorporating a prostate-specific amplification feedback loop

Gene Therapy
J WoraratanadharmJ-Y Dong

Abstract

Development of novel therapeutic agents is needed to address the problems of locally recurrent, metastatic, and advanced hormone-refractory prostate cancer. We have constructed a novel complex adenovirus (Ad) vector regulation system that incorporates both the prostate-specific ARR2PB promoter and a positive feedback loop using the TRE promoter to enhance gene expression. This regulation strategy involves the incorporation of the TRE upstream of the prostate-specific ARR2PB promoter to enhance its activity with Tet regulation. The expressions of both GFP and tTA were placed under the control of these TRE-ARR2PB promoters, so that in the cells of prostate origin a positive feedback loop would be generated. This design greatly enhanced GFP reporter expression in prostate cancer cells, while retaining tight control of expression in nonprostate cancer cells, even at an MOI as high as 1000. This novel positive feedback loop with prostate specificity (PFLPS) regulation system we have developed may have broad applications for expressing not only high levels of toxic proteins in cancer cells, but alternatively could also be manipulated to regulate essential genes in a highly efficient conditionally replicative adenovirus vector specifi...Continue Reading

References

Jun 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·M Gossen, H Bujard
Jun 9, 1995·The Journal of Biological Chemistry·J R HoweC Schmauss
Sep 27, 1994·Proceedings of the National Academy of Sciences of the United States of America·P A FurthL Hennighausen
Oct 1, 1996·Proceedings of the National Academy of Sciences of the United States of America·A KistnerH Bujard
May 27, 1999·Journal of Molecular Endocrinology·S KasperR J Matusik
Oct 6, 2000·Molecular Therapy : the Journal of the American Society of Gene Therapy·M L HyerJ S Norris
Sep 6, 2001·Journal of the National Cancer Institute·F AndrianiM Marcelli
Nov 16, 2001·Molecular Therapy : the Journal of the American Society of Gene Therapy·S RubinchikJ Y Dong
Dec 4, 2001·Advanced Drug Delivery Reviews·Y S Haviv, D T Curiel
Feb 15, 2002·Frontiers of Radiation Therapy and Oncology·R Kirschner-Hermanns, G Jakse
Apr 3, 2002·Trends in Molecular Medicine·David KirnCaroline J Springer
Apr 12, 2002·World Journal of Surgery·Kazuyuki YazawaF Charles Brunicardi
May 15, 2002·Molecular Urology·T ShirakawaL W Chung
Jun 12, 2002·Current Treatment Options in Oncology·E A KleinC Zippe
Aug 23, 2002·Critical Reviews in Oncology/hematology·Ruth Kirschner-Hermanns, Gerhard Jakse
Feb 5, 2003·European Urology·E J H Meuleman, P F A Mulders
Jul 2, 2003·Cancer Gene Therapy·Ja Young SeolChoon-Taek Lee
Aug 30, 2003·Urology·Wim JongmansEgbert Oosterwijk

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Citations

Mar 25, 2006·Future Oncology·John Y Dong, Jan Woraratanadharm
Apr 26, 2007·Molecular Therapy : the Journal of the American Society of Gene Therapy·Marxa L FigueiredoLily Wu
May 26, 2010·Molecular Pharmaceutics·Hiroshi OchiaiHiroyuki Kamiya

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