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©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 21, 2018; 24(19): 2095-2107
Published online May 21, 2018. doi: 10.3748/wjg.v24.i19.2095
Published online May 21, 2018. doi: 10.3748/wjg.v24.i19.2095
Detection of hyper-conserved regions in hepatitis B virus X gene potentially useful for gene therapy
Carolina González, David Tabernero, Maria Francesca Cortese, Rosario Casillas, Cristina Godoy, Sara Sopena, Ariadna Rando, Marçal Yll, Rosa Lopez-Martinez, Francisco Rodríguez-Frías, Liver Pathology Unit, Departments of Biochemistry and Microbiology, Hospital Universitari Vall d’Hebron, Universitat Autònoma de Barcelona, Barcelona 08035, Spain
David Tabernero, Josep Gregori, Mar Riveiro-Barciela, Sara Sopena, Josep Quer, Rafael Esteban, Maria Buti, Francisco Rodríguez-Frías, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid 28029, Spain
Maria Francesca Cortese, Josep Gregori, Rosario Casillas, Cristina Godoy, Marçall Yll, Josep Quer, Liver Unit, Liver Disease Laboratory-Viral Hepatitis, Vall d’Hebron Institut Recerca-Hospital Universitari Vall d’Hebron, Universitat Autònoma de Barcelona, Barcelona 08035, Spain
Josep Gregori, Roche Diagnostics SL, Sant Cugat del Vallès 08174, Spain
Mar Riveiro-Barciela, Rafael Esteban and Maria Buti, Liver Unit, Department of Internal Medicine, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona 08035, Spain
Author contributions: Rodríguez-Frías F designed the research; Cortese MF coordinated the research; González C and Tabernero D equally contributed to design the experiments; González C, Casillas R, Godoy C, Sopena S and Rando A performed the experiments; González C, Tabernero D and Gregori J analyzed data acquired during the experiments and interpreted the results; González C, Tabernero D, Cortese MF and Riveiro-Barciela M drafted the manuscript; Yll M, Lopez-Martinez R, Buti M, Quer J, Esteban R and Rodríguez-Frías F critically reviewed the manuscript.
Supported by the Instituto de Salud Carlos III, No. PI15/00856; and the European Regional Development Fund (ERDF), No. PI15/00856.
Institutional review board statement: The study was reviewed and approved by the Clinical Research Ethics Committee (CEIC) of Hospital Universitari Vall d’Hebron.
Conflict-of-interest statement: Josep Gregori is an employee of Roche Diagnostics, SL.
Data sharing statement: No additional data are available.
Open-Access: 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/
Correspondence to: Maria Francesca Cortese, PhD, Research Scientist, Liver Pathology Unit, Departments of Biochemistry and Microbiology, Hospital Universitari Vall d’Hebron, Universitat Autònoma de Barcelona, Passeig Vall d’Hebron 119-129, Barcelona 08035, Spain. maria.cortese@vhir.org
Telephone: +34-932-746000/6858
Received: February 16, 2018
Peer-review started: February 17, 2018
First decision: March 9, 2018
Revised: March 26, 2018
Accepted: May 6, 2018
Article in press: May 6, 2018
Published online: May 21, 2018
Processing time: 90 Days and 12.5 Hours
Peer-review started: February 17, 2018
First decision: March 9, 2018
Revised: March 26, 2018
Accepted: May 6, 2018
Article in press: May 6, 2018
Published online: May 21, 2018
Processing time: 90 Days and 12.5 Hours
Core Tip
Core tip: Hepatitis B virus (HBV) is not cured with classic treatments, and liver disease can progress by persistence and expression of covalently-closed circular DNA. Gene therapy with small interference RNA may be an effective approach to ensure inhibition of viral expression and disease progression, and hepatitis B virus X gene (HBX) transcripts could be optimal targets for this therapy. This study includes patients with different HBV genotypes and clinical stages to cover many clinical and virological situations. Using next-generation sequencing, we found two hyper-conserved HBX regions, candidates for small interference RNA therapy, which could enable pan-genotypic inhibition of HBV expression, regardless of the patients’ disease status.