Diseases of the immune/inflammatory system are a widespread and significant source of pain and cost to global populations. Common, diverse, and highly variable in both symptoms and underlying mechanisms, these inflammatory disorders are challenging to address in the clinic. Critical for the development, validation, and clinical efficacy of anti-inflammatory therapeutics are bio-monitoring technologies that allow clinicians to monitor the progression of autoimmune disorders and their response to anti-inflammatory drugs. However, such technologies often suffer significant problems in their timing, means of monitoring, and lack of responsiveness to cellular-level changes in inflammatory bioactivity. Here, I describe efforts to coordinate advances in virology, cell biology, and biomedical engineering to develop and validate an in vivo real-time biosensor of inflammation based on cutaneous gene delivery strategies. Chapter 1 shows a survey of adeno-associated virus infectivity in skin cells, designed to facilitate inflammation reporter development in vitro and in vivo. Chapter 2 describes the development and validation of prototype inflammation sensors in the skin of an animal model. Together, these results lay the groundwork for development of an in vivo inflammation biosensor capable of providing real-time information on inflammatory bioactivity from the skin of a living animal.