Publication Name	World Journal of Hepatology
Manuscript ID	37312
Country	Germany

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
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.
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

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 Company 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

ISSN	1948-5182 (online)
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