Currently, national and supranational governments are developing mission-oriented policy, thereby following the ideas on how to design innovation policy as developed by Mariana Mazzucato (2011; 2017; 2018). Mission-orientated innovation policy is seen here as a manifestation of what Schot & Steinmueller (2018) identified as ‘transformative innovation policy’, whereby, through science, technology and innovation policies, societal needs are met and issues of sustainable and inclusive societies are addressed at a more fundamental level. The question that guides our projects is: How can transformative innovation policy profit from lessons about ways to deal with challenges in processes of knowledge production for sustainable innovation? With our research, next to a scientific contribution, we aim to inform innovation policies in the Netherlands with such components of mission orientation in its design and its goals. Three challenges for science-based innovation that are informative for innovation policy were identified earlier (Blankesteijn, 2019). The challenges relate to 1. the lack of legitimacy of the actors involved in innovative technology development for sustainable practices 2. decreasing support for a strong role of the government in innovation 3. regulatory barriers preventing the upscaling of technologies aiming at sustainable innovation. Research projects that are currently undertaken aim at further developing such an understanding, based on identifying barriers and drivers that can be deduced from processes of knowledge production and their relative success in upscaling the technologies developed. Using a mixed-method multiple case study research design, the sectors researched are water management sector, the energy sector and health care sector. These sectors are 1. strongly science driven and 2. experience an urgent need to become more sustainable 3. develop experiments in order to maximize the chance of the technology being upscaled to a more systemic level. With the help of insights based on research in three sectors, eventually overall lessons are drawn on ways to design innovation policy to optimally support such initiatives. These will be communicated through scientific papers. These lessons will be co-developed with and distributed by practitioners, policy makers and scientists working as physicists and chemists as well. The projects run in the period 2017-2024.