Enhancers Are Major Targets for Murine Leukemia Virus Vector Integration Suk See De Ravin, Ling Su, Narda Theobald, Uimook Choi, Janet L. Macpherson, Michael Poidinger, Geoff Symonds, Susan M. Pond, Andrea L. Ferris, Stephen H. Hughes, Harry L. Malech, and Xiaolin Wu J. Virol. April 2014 88:8 4504-4513; published ahead of print 5 February 2014, doi:10.1128/JVI.00011-14
Abstract:
Retroviral vectors have been used in successful gene therapies. However, in some patients, insertional mutagenesis led to leukemia or myelodysplasia. Both the strong promoter/enhancer elements in the long terminal repeats (LTRs) of murine leukemia virus (MLV)-based vectors and the vector-specific integration site preferences played an important role in these adverse clinical events. MLV integration is known to prefer regions in or near transcription start sites (TSS). Recently, BET family proteins were shown to be the major cellular proteins responsible for targeting MLV integration. Although MLV integration sites are significantly enriched at TSS, only a small fraction of the MLV integration sites (