The demand for insulin fluctuates with blood glucose levels, presenting a special challenge for would-be gene therapists. In the 23 November Nature, Lee et al. present their solution, which causes remission of autoimmune diabetes in mice for at least 8 months (Nature 2000, 408:483-488). A truncated insulin gene removes the need for proteolytic processing, a hepatocyte-specific, glucose-responsive promoter supplies the correct dosage, and an adeno-associated virus (AAV) delivers the necessary DNA to liver cells. Glucose challenge elicited the correct response of increased insulin production, although this response was robust 2 hours after challenge and continued for almost 6 hours, as compared to the 30 minute response time and 1 hour duration seen in healthy animals. This delay probably arises because the gene therapy is controlled at the level of transcription, whereas insulin production is normally controlled at the level of secretion. The sustained response caused...

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