We examine how the National Nanotechnology Initiative (NNI), a recent U.S. government science and technology (ST) program launched in 2000, affects the nature of university research in nanotechnology. We characterize the NNI as a policy intervention that targets the commercialization of technology and a focused research direction to promote national economic growth. As such, we expect that the NNI has brought about unintended consequences in the direction of university-industry knowledge flows and the characteristics of university research output in nanotechnology. Using a difference-in-differences analysis of U.S. nanotechnology patents filed between 1996 and 2007, we find that, after the NNI, U.S. universities have significantly increased knowledge inflows from the industry, reduced the branching-out to novel technologies, narrowed down the research scope, and become less likely to generate technological breakthroughs, as compared to other U.S. and non-U.S. research institutions. Our findings suggest that, at least in the case of the NNI, targeted government ST programs may increase the efficiency of university research, but potentially do so at a price. (C) 2013 Elsevier B.V. All rights reserved.