Hafkemeyer P, Brinkmann U, Brinkmann E, Pastan I, Blum HE, Baumert TF. Pseudomonas exotoxin antisense RNA selectively kills hepatitis B virus infected cells. World J Gastroenterol 2008; 14(18): 2810-2817 [PMID: 18473403 DOI: 10.3748/wjg.14.2810]
Corresponding Author of This Article
Peter Hafkemeyer, MD, Department of Medicine II, University Hospital Freiburg, Hugstetterstrasse 55, Freiburg D-79106, Germany. phafkemeyer@gmx.net
Article-Type of This Article
Viral Hepatitis
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Ira Pastan, National Cancer Institute, National Institutes of Health, Bethesda, United States
Thomas F Baumert, Inserm unit 748, Université Louis Pasteur, 3 Rue Koeberle, Strasbourg F-67000, France
Author contributions: Hafkemeyer P designed research/performed experiments/wrote paper; Brinkmann E, Brinkmann U performed experiments; Pastan I, Blum HE designed research; Baumert TF cloned plasmids/performed assays.
Correspondence to: Peter Hafkemeyer, MD, Department of Medicine II, University Hospital Freiburg, Hugstetterstrasse 55, Freiburg D-79106, Germany. phafkemeyer@gmx.net
Telephone: +49-761-2703403
Fax: +49-761-2703610
Received: December 15, 2007 Revised: April 9, 2008 Published online: May 14, 2008
Abstract
AIM: To present an approach for selectively killing retrovirus-infected cells that combines the toxicity of Pseudomonas exotoxin (PE) and the presence of reverse transcriptase (RT) in infected cells.
METHODS: PE antisense toxin RNA has palindromic stem loops at its 5’ and 3’ ends enabling self-primed generation of cDNA in the presence of RT. The RT activity expressed in retrovirus-infected cells converts “antisense-toxin-RNA” into a lethal toxin gene exclusively in these cells.
RESULTS: Using cotransfection studies with PE-expressing RNAs and β-gal expressing reporter plasmids, we show that, in HepG2 and HepG2.2.15 hepatoma cells as well as in duck hepatitis B virus (DHBV) infected cells, HBV or DHBV-polymerase reverse transcribe a lethal cDNA copy of an antisense toxin RNA, which is composed of sequences complementary to a PE gene and eukaryotic transcription and translation signals.
CONCLUSION: This finding may have important implications as a novel therapeutic strategy aimed at the elimination of HBV infection.
