Publication Name	World Journal of Hepatology
Manuscript ID	37312
Country	Germany

Received	2017-12-07 21:28
Peer-Review Started	2017-12-08 03:06
To Make the First Decision	2017-12-18 08:31
Return for Revision	2017-12-18 10:45
Revised	2018-02-01 22:17
Second Decision	2018-02-23 04:43
Accepted by Journal Editor-in-Chief
Accepted by Executive Editor-in-Chief	2018-03-01 07:52
Articles in Press	2018-03-01 07:52
Publication Fee Transferred
Edit the Manuscript by Language Editor
Typeset the Manuscript	2018-03-02 06:17
Publish the Manuscript Online	2018-03-04 12:36

ISSN	1948-5182 (online)
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/
Copyright	© The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
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Category	Gastroenterology & Hepatology
Manuscript Type	Basic Study
Article Title	Homologous recombination mediates stable Fah gene integration and phenotypic correction in tyrosinaemia mouse-model
Manuscript Source	Invited Manuscript
All Author List	Norman Junge, Qinggong Yuan, Thu Huong Vu, Simon Krooss, Christien Bednarski, Asha Balakrishnan, Toni Cathomen, Michael P Manns, Ullrich Baumann, Amar Deep Sharma and Michael Ott
ORCID	Author(s) ORCID Number Norman Junge http://orcid.org/0000-0002-3099-2667 Qinggong Yuan http://orcid.org/0000-0001-8446-8193 Thu Huong Vu http://orcid.org/0000-0002-3050-9583 Simon Krooss http://orcid.org/0000-0001-6372-395X Christien Bednarski http://orcid.org/0000-0002-4787-3293 Asha Balakrishnan http://orcid.org/0000-0002-1366-3386 Toni Cathomen http://orcid.org/0000-0002-7757-4630 Michael P Manns http://orcid.org/0000-0002-4485-8856 Ullrich Baumann http://orcid.org/0000-0002-0162-0266 Amar Deep Sharma http://orcid.org/0000-0003-3599-2372 Michael Ott http://orcid.org/0000-0002-1245-358X
Funding Agency and Grant Number
Corresponding Author	Michael Ott, MD, Full Professor, TWINCORE, Centre for Experimental and Clinical Infection Research, Feodor-Lynen-Str 7, Hannover 30625, Germany. ott.michael@mh-hannover.de
Key Words	Gene therapy; AAV8; Liver based metabolic disease; Targeted integration; ROSA26; Paediatric liver disease
Core Tip	Recombinant adeno-associated virus (rAAV) has been explored for gene delivery in various murine models of hereditary liver disease, but in young children transgene expression from AAV-epigenomes diminishes over time. We thus explored, whether homologous recombination-mediated targeted gene addition of the fumarylacetoacetate hydrolase (Fah) gene would stably correct tyrosinaemia in rapidly proliferating livers of Fah-/- mice. Here, we report successful homologous recombination-mediated genome editing of a Fah gene expression cassette at the Rosa26 locus by rAAV8. We demonstrate that this approach corrects the phenotype and is long lasting in a proliferating state of the liver, as shown by serial transplantation.
Publish Date	2018-03-04 12:36
Citation	Junge N, Yuan Q, Huong Vu T, Krooss S, Bednarski C, Balakrishnan A, Cathomen T, Manns MP, Baumann U, Sharma AD, Ott M. Homologous recombination mediates stable Fah gene integration and phenotypic correction in tyrosinaemia mouse-model. World J Hepatol 2018; 10(2): 277-286
URL	http://www.wjgnet.com/1948-5182/full/v10/i2/277.htm
DOI	http://dx.doi.org/10.4254/wjh.v10.i2.277

Full Article (PDF)	WJH-10-277.pdf
Full Article (Word)	WJH-10-277.doc
The ARRIVE Guidelines	37312-ARRIVE guideline statement.pdf
Manuscript File	37312-Review.docx
Answering Reviewers	37312-Answering reviewers.pdf
Audio Core Tip	37312-Audio core tip.mp3
Conflict-of-Interest Disclosure Form	37312-Conflict-of-interest statement.pdf
Copyright License Agreement	37312-Copyright assignment.pdf
Institutional Animal Care and Use Committee Approval Form or Document	37312-Institutional animal care and use committee statement.pdf
Institutional Review Board Approval Form or Document	37312-Institutional Review Board Approval Form or Document.pdf
Non-Native Speakers of English Editing Certificate	37312-Language certificate.pdf
Peer-review Report	37312-Peer-review(s).pdf
Scientific Misconduct Check	37312-Scientific misconduct check.pdf
Scientific Editor Work List	37312-Scientific editor work list.pdf