During a period of regional structural change, the socio-institutional structure and the techno-economic structure are temporarily decoupled due to the relative inertia of the former compared with the rapid changes in the latter. The lag in the coevolution of the socio-institutional and techno-economic structures generates inefficiencies and instabilities, causing transitional failure. In exploring the rationale for policy intervention, this paper examines the actors that aim to influence socio-institutional changes in Medellín, Colombia. It finds that the private sector, under the informal leadership of the Grupo Empresarial Antioqueño, has played the role of institutional entrepreneurs to influence socio-institutional changes. In regions located on the knowledge periphery, in which the socio-institutional structure has not yet fully coevolved with the novel techno-economic structure, policy-makers can induce socio-institutional changes by learning from regions that have already transitioned to the novel techno-economic paradigm.