Skip to content
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
The fetal mouse is a sensitive genotoxicity model that exposes lentiviral-associated mutagenesis resulting in liver oncogenesis
Molecular Therapy, Volume 21, No. 2, Year 2013
Notification
URL copied to clipboard!
Description
Genotoxicity models are extremely important to assess retroviral vector biosafety before gene therapy. We have developed an in utero model that demonstrates that hepatocellular carcinoma (HCC) development is restricted to mice receiving nonprimate (np) lentiviral vectors (LV) and does not occur when a primate (p) LV is used regardless of woodchuck post-translation regulatory element (WPRE) mutations to prevent truncated X gene expression. Analysis of 839 npLV and 244 pLV integrations in the liver genomes of vector-treated mice revealed clear differences between vector insertions in gene dense regions and highly expressed genes, suggestive of vector preference for insertion or clonal outgrowth. In npLV-associated clonal tumors, 56% of insertions occurred in oncogenes or genes associated with oncogenesis or tumor suppression and surprisingly, most genes examined (11/12) had reduced expression as compared with control livers and tumors. Two examples of vector-inserted genes were the Park 7 oncogene and Uvrag tumor suppressor gene. Both these genes and their known interactive partners had differential expression profiles. Interactive partners were assigned to networks specific to liver disease and HCC via ingenuity pathway analysis. The fetal mouse model not only exposes the genotoxic potential of vectors intended for gene therapy but can also reveal genes associated with liver oncogenesis. © The American Society of Gene &Cell Therapy.
Authors & Co-Authors
Nowrouzi, Ali
Germany, Heidelberg
National Centre for Tumorigenesis Nct
Cheung, Wing T.
United Kingdom, London
Imperial College London
Li, Tingting
China, Beijing
Tsinghua University
China, Beijing
Peking University
Zhang, Xuegong
China, Beijing
Tsinghua University
China, Beijing
Peking University
Arens, Anne
Germany, Heidelberg
National Centre for Tumorigenesis Nct
Paruzynski, Anna
Germany, Heidelberg
National Centre for Tumorigenesis Nct
Waddington, Simon N.
United Kingdom, London
University College London
Osejindu, Emma
United Kingdom, Uxbridge
Brunel University London
Reja, Safia
United Kingdom, Uxbridge
Brunel University London
Von-Kalle, Christof
United States, Cincinnati
Cincinnati Children's Hospital Medical Center
Wang, Yoahe
United Kingdom, London
Barts and the London School of Medicine and Dentistry
Al-Allaf, Faisal Ahmad
United Kingdom, London
Imperial College London
Saudi Arabia, Makkah
Umm Al-qura University
Gregory, Lisa G.
United Kingdom, London
Imperial College London
Themes, Matthew
United Kingdom, London
Ucl Great Ormond Street Institute of Child Health
Holder, Maxine V.
United Kingdom, London
Cancer Research uk
Dighe, Niraja M.
United Kingdom, London
Imperial College London
Ruthe, Ali T.
United Kingdom, London
Imperial College London
Buckley, Suzanne M.K.
United Kingdom, London
University College London
Bigger, Brian W.
United Kingdom, Manchester
Faculty of Biology, Medicine and Health
Montini, Eugenio
Italy, Milan
San Raffaele Telethon Institute for Gene Therapy
Thrasher, Adrian James
United Kingdom, London
Ucl Great Ormond Street Institute of Child Health
Andrews, Robert M.
United Kingdom, Hinxton
Wellcome Sanger Institute
Roberts, Terry P.
United Kingdom, Uxbridge
Brunel University London
Newbold, Robert Frank
United Kingdom, Uxbridge
Brunel University London
Coutelle, Charles C.
United Kingdom, London
Imperial College London
Schmidt, Manfred C.
Germany, Heidelberg
National Centre for Tumorigenesis Nct
Themis, Michael
United Kingdom, London
Imperial College London
United Kingdom, Uxbridge
Brunel University London
Statistics
Citations: 27
Authors: 27
Affiliations: 14
Identifiers
Doi:
10.1038/mt.2012.224
ISSN:
15250016
e-ISSN:
15250024
Research Areas
Cancer
Genetics And Genomics