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The article gives a comparative analysis of the innovation and technological development in Russia and foreign countries. The paper shows that in the innovation sector, Russia lags behind most of the developed and developing countries: Russia has almost left the market of high technologies; main costs for innovations are implemented in the sectors of low and medium technology industries. Self-sufficiency of Russian economy for a number of the major types of production equipment is significantly below than the threshold marks determined by the requirements of national security. The article demonstrated the differentiation in the innovative development of the Russian regions. The study of the Russian innovation space has shown that in the periphery, there are sufficiently intense processes of the attenuation of science, which creates serious problems for the growth of innovative impulses across the country. The authors present the methodology for integrated assessment of regional innovative security. The appropriate calculations for regions of the Ural Federal District are performed. The article identifies the most critical factors for innovative sustainability of these regions. The authors have made a forecast as well as built the projected trajectories of the innovative security level of the Ural Federal District using the modernized method of Hurst. We have formulated the main barriers to the innovative development of the Russian regions. The article presents the methodological approaches to the substantiation of the priorities for the formation of the innovative system of regions including the specific features of their science and industry. The authors propose the methodology for the formal evaluation of the creation of a regional innovation activity centers aimed at supporting the competitiveness of the enterprises of different technological level. The paper presents calculation results for the priority of the formation of the centers of innovation activity aimed at supporting the development of industries of different technological level on the example of the regions of the Ural Federal District which is one of the leading Russian regions in the innovative and productive potentials.