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Transmedia design, which involves extending a narrative from one medium to another, offers a context for potentially rich, interdisciplinary learning. We explored these opportunities by creating a week-long workshop to guide 7th-grade student teams in designing games based on comic books about viruses. This design case describes the framework and rationale behind our design choices. It illustrates our experiences by drawing on field note observations and audio recordings, student-generated design artifacts, student and facilitator interviews, and planning documentation from across two iterations of the workshop. We reflect on our experiences in attempting to balance (1) the dual focus of the workshop on science learning and game design through our choices of comic and game genres; and (2) the ability for students to be both autonomous and to receive necessary guidance through our enforcement of design constraints and interdependent team roles. We also reflect on the contextual factors that mediated our work, including students’ existing interests and peer relations, their teachers’ involvement, and our own team’s shifting expertise as membership changed from one iteration to the next. Among other things, our experiences highlight the importance of designing to allow for change, particularly as learning through collaborative transmedia game design can occur in unanticipated ways. Finally, we reflect on plans for future iterations of this workshop.