PMID: 9448307Mar 14, 1998Paper

Inhibition of HPV-16 E6/E7 immortalization of normal keratinocytes by hairpin ribozymes

Proceedings of the National Academy of Sciences of the United States of America
L M Alvarez-SalasJ A DiPaolo

Abstract

HPV-16 E6 and E7 genes are required to efficiently immortalize a broad spectrum of cell types including cervical keratinocytes. Therefore, the E6/E7 genes can be considered relevant targets for anti-cancer therapy. We produced several engineered hairpin (HP) ribozymes to specifically disrupt HPV-16 E6/E7 mRNA. After extensive biochemical characterization, one anti-E6 HP ribozyme (R434) was selected for in vivo testing because of its superior catalytic capabilities. When expressed in cis, R434 efficiently inhibited E6 in vitro translation. Cis-expression of the HP ribozyme with HPV-16 E6/E7 genes in normal human keratinocytes reduced the growth rate and prevented immortalization. RNA analysis by reverse transcription-PCR showed that E6/E7 transcripts were cleaved in post-transfected cells and virtually were eliminated after long term expression. Of interest, an inactive version of the HP also was able to significantly affect the immortalizing ability of E6/E7, probably through passive hybridization. The combination of passive and cleaving antisense RNA therefore is established as an effective inhibitor of HPV-16 E6/E7 immortalization.

References

Nov 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·J O OjwangJ Rappaport
Jan 1, 1992·Advances in Experimental Medicine and Biology·J J Rossi, N Sarver
Jan 1, 1991·Antisense Research and Development·J S Cohen
May 1, 1988·Genes & Development·J Walder
Nov 25, 1988·JAMA : the Journal of the American Medical Association·T R Cech
Jun 13, 1989·Biochemistry·A Hampel, R Tritz
Mar 15, 1994·Proceedings of the National Academy of Sciences of the United States of America·S EfratN Fleischer
Mar 1, 1995·Nature Medicine·J D ThompsonD T Stinchcomb
Jan 1, 1995·Antisense Research and Development·G L Nichols
Sep 20, 1995·Journal of the National Cancer Institute·M H Schiffman
Apr 22, 1995·Lancet·M KiehntopfF Herrmann
May 4, 1995·Cancer Letters·L M Alvarez-SalasJ A DiPaolo
Jan 1, 1994·Annual Review of Microbiology·H zur Hausen, E M de Villiers
Apr 1, 1994·Journal of Molecular Endocrinology·S J Persaud, P M Jones
Mar 25, 1994·Nucleic Acids Research·P AndersonA Hampel
Nov 11, 1993·Nucleic Acids Research·P CrisellW James
Jul 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·M YuF Wong-Staal

❮ Previous
Next ❯

Citations

Feb 22, 2003·Current Treatment Options in Oncology·Samir N Khleif
Nov 20, 1998·Current Opinion in Biotechnology·P J WelchF Wong-Staal
Apr 28, 2001·Cytokine & Growth Factor Reviews·A E KoromilasG Matlashewski
Nov 26, 2008·Oncogene·M ThomasL Banks
Dec 13, 2005·Cancer Gene Therapy·E J Shillitoe
Aug 19, 2008·Oligonucleotides·Guillermo Aquino-JarquinLuis M Alvarez-Salas
Sep 8, 2009·Oligonucleotides·Pablo Reyes-Gutiérrez, Luis M Alvarez-Salas
Nov 16, 2012·Journal of Virology·Xueli FanJason J Chen
Jun 1, 2000·Proceedings of the National Academy of Sciences of the United States of America·K ButzF Hoppe-Seyler
May 5, 2007·Expert Opinion on Biological Therapy·John Doorbar, Heather Griffin
Jul 23, 2004·Expert Opinion on Biological Therapy·Joseph A DiPaolo, Luis M Alvarez-Salas
Sep 12, 2007·Archives of Medical Research·Miguel A Márquez-GutiérrezLuis M Alvarez-Salas
Apr 17, 2003·FEMS Microbiology Reviews·Elena Puerta-FernándezAlfredo Berzal-Herranz
Jul 31, 2007·Biochemical and Biophysical Research Communications·Magali LagrangeFrançois Deryckere
Feb 8, 2003·Molecular Therapy : the Journal of the American Society of Gene Therapy·Wei-Hua PanGary A Clawson
Nov 6, 2003·Molecular Therapy : the Journal of the American Society of Gene Therapy·Mitsuo YoshinouchiKenji Yamato
Apr 16, 2013·Otolaryngology--head and Neck Surgery : Official Journal of American Academy of Otolaryngology-Head and Neck Surgery·Alice L TangMark E Prince
Mar 3, 2005·World Journal of Gastroenterology : WJG·Ting-Ting LiDai-Ming Fan
Jun 13, 2018·Journal of Cellular and Molecular Medicine·Yonghao TianWeifang Zhang
Aug 6, 1999·Antisense & Nucleic Acid Drug Development·J Albuquerque-SilvaS Houard
May 15, 2002·The Journal of Biological Chemistry·Attila A SeyhanJohn M Burke
Jun 3, 2020·Medicinal Research Reviews·Avinash KumarSuvarna G Kini
Jul 16, 2017·Scientific Reports·Sumitra ShankarM Radhakrishna Pillai
Feb 8, 2002·World Journal of Gastroenterology : WJG·Yu-Hu SongKuo-Huan Liang
Oct 13, 2020·Frontiers in Oncology·Jeremy Gbenakpon AugustinCécile Badoual
Mar 15, 2000·Journal of Molecular Biology·M J Fedor
Mar 14, 2000·Seminars in Cancer Biology·F Mantovani, L Banks
Aug 30, 2002·Biochemical and Biophysical Research Communications·Minjie DuJason J Chen
Jun 7, 2014·Journal of Medicinal Chemistry·Manuela DonalisioOriana Tabarrini

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antivirals (ASM)

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

Antivirals

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.