UCL logo

UCL Discovery

UCL home » Library Services » Electronic resources » UCL Discovery

Lentiviral Vector Integration Profiles Differ in Rodent Postmitotic Tissues

Bartholomae, CC; Arens, A; Balaggan, KS; Yanez-Munoz, RJ; Montini, E; Howe, SJ; Paruzynski, A; ... Schmidt, M; + view all (2011) Lentiviral Vector Integration Profiles Differ in Rodent Postmitotic Tissues. MOL THER , 19 (4) 703 - 710. 10.1038/mt.2011.19.

Full text not available from this repository.

Abstract

Lentiviral vectors with self-inactivating (SIN) long terminal repeats (LTRs) are promising for safe and sustained transgene expression in dividing as well as quiescent cells. As genome organization and transcription substantially differs between actively dividing and postmitotic cells in vivo, we hypothesized that genomic vector integration preferences might be distinct between these biological states. We performed integration site (IS) analyses on mouse dividing cells (fibroblasts and hematopoietic progenitor cells (HPCs)) transduced ex vivo and postmitotic cells (eye and brain) transduced in vivo. As expected, integration in dividing cells occurred preferably into gene coding regions. In contrast, postmitotic cells showed a close to random frequency of integration into genes and gene spare long interspersed nuclear elements (LINE). Our studies on the potential mechanisms responsible for the detected differences of lentiviral integration suggest that the lowered expression level of Psip1 reduce the integration frequency in vivo into gene coding regions in postmitotic cells. The motif TGGAA might represent one of the factors for preferred lentiviral integration into mouse and rat Satellite DNA. These observations are highly relevant for the correct assessment of preclinical biosafety studies, indicating that lentiviral vectors are well suited for safe and effective clinical gene transfer into postmitotic tissues.

Type: Article
Title: Lentiviral Vector Integration Profiles Differ in Rodent Postmitotic Tissues
DOI: 10.1038/mt.2011.19
Keywords: GENE-THERAPY, SITE SELECTION, REPOPULATING CELLS, HIV-1 INTEGRATION, MOUSE MODEL, DNA DUPLEX, LEDGF/P75, EFFICIENT, REPEATS, REGIONS
UCL classification: UCL > School of Life and Medical Sciences
UCL > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
UCL > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology > Institute of Ophthalmology - Genetics
UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Child Health
URI: http://discovery.ucl.ac.uk/id/eprint/1304805
Downloads since deposit
0Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item