A typical retrovirus vector (in blue) can activate a cellular oncogene (in red) through either the enhancers (top arrows) or promoters (bottom arrows) present in the U3 regions of the virus long terminal repeats (LTRs). Generation of a self-inactivating (SIN) vector by deletion of the U3 regions in the vector LTRs and inclusion of an internal enhancer/promoter (the U3 region in this case) should reduce, but not eliminate, these potential interactions. Modlich and colleagues show that these changes reduce the rate of vector-mediated transformation by approximately 12-fold (based on the replating efficiencies of transduced bone marrow). Note that enhancers can also activate oncogenes in the 5′ direction (not shown).