Inhibition of papilloma progression by antisense oligonucleotides targeted to HPV11 E6/E7 RNA

Gene Therapy
G A ClawsonN D Christensen

Abstract

Human papillomaviruses (HPVs) are recognized as important human pathogens, causing a spectrum of hyperproliferative lesions from benign warts to cervical dysplasias/carcinomas. HPV-associated lesions require continued production of the oncogenic E6/E7 proteins, which are encoded by either bicistronic or overlapping mRNAs. Here we targeted the E6/E7 mRNA of HPV11, a type implicated in causation of genital warts, using molecular reagents. Accessible sites in the HPV11(E6/E7) RNA were identified using library selection protocols, and nucleic acids (DNAzymes, antisense oligonucleotides) targeted to these sites were constructed, and tested in cell culture and on human foreskin grafts. While DNAzymes were at least equally effective in cell culture, antisense oligonucleotides targeted to the region surrounding one of the library-selected sites (ASO(407)) proved most effective in blocking progression of HPV11-induced papillomas in human foreskin grafts on immunodeficient mice. In total, 11 papillomas were treated with ASO(407). Of these, four of seven small papillomas treated with ASO(407) showed loss of detectable virus by in situ hybridization (ISH), and in all four of these, papillomas were no longer evident grossly or histologicall...Continue Reading

References

Feb 1, 1992·Human Pathology·M H StolerT R Broker
May 1, 1992·The Journal of General Virology·N D ChristensenR F Rando
Jul 9, 1992·International Journal of Cancer. Journal International Du Cancer·M von Knebel DoeberitzM Dürst
Jun 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·J L BrandsmaE A Johnson
Nov 1, 1990·Journal of Virology·N D ChristensenP A Welsh
Jan 1, 1986·American Journal of Obstetrics and Gynecology·W D LancasterA B Jenson
Feb 1, 1987·Journal of Virology·J W KreiderJ A Weber
Jun 7, 1994·Proceedings of the National Academy of Sciences of the United States of America·R J SlebosK R Cho
Mar 1, 1997·The Journal of Pathology·J M Walboomers, C J Meijer
Jul 1, 1997·Nature Biotechnology·N S TempletonG N Pavlakis
Mar 5, 1998·Journal of the American Academy of Dermatology·K R BeutnerJ M Douglas
Aug 19, 1999·The Journal of Pathology·C S Herrington
Aug 19, 1999·The Journal of Pathology·J M WalboomersN Muñoz
Feb 7, 2003·The New England Journal of Medicine·Nubia MuñozUNKNOWN International Agency for Research on Cancer Multicenter Cervical Cancer Study Group
Feb 8, 2003·Molecular Therapy : the Journal of the American Society of Gene Therapy·Wei-Hua PanGary A Clawson
Mar 16, 2004·Methods in Molecular Biology·Wei-Hua Pan, Gary A Clawson
Apr 20, 2004·Molecular Therapy : the Journal of the American Society of Gene Therapy·Wei-Hua PanGary A Clawson

❮ Previous
Next ❯

Citations

Jul 4, 2008·Journal of Lower Genital Tract Disease·Edward John Mayeaux, Charles Dunton
May 25, 2006·Frontiers in Bioscience : a Journal and Virtual Library·Zhi-Ming Zheng, Carl C Baker
Mar 17, 2015·Expert Opinion on Biological Therapy·Alesya A FokinaJean-Christophe François
Mar 4, 2015·Advanced Drug Delivery Reviews·Yuhua WangLeaf Huang
Aug 10, 2007·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Christian HillerMichael Dahm
Jul 13, 2006·Antiviral Research·Robert Snoeck
Jan 28, 2006·Journal of Cellular Biochemistry·Wei-Hua Pan, Gary A Clawson
Sep 14, 2007·Biomarkers : Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals·Dejan BaskićNebojsa Arsenijević

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antisense Oligonucleotides: ND

This feed focuses on antisense oligonucleotide therapies such as Inotersen, Nusinursen, and Patisiran, in neurodegenerative diseases including amyotrophic lateral sclerosis.

CREs: Gene & Cell Therapy

Gene and cell therapy advances have shown promising outcomes for several diseases. The role of cis-regulatory elements (CREs) is crucial in the design of gene therapy vectors. Here is the latest research on CREs in gene and cell therapy.