Targeting gene expression to specific tissues could overcome some of the obstacles at making gene therapy effective. Researchers at the University of Pennsylvania School of Medicine (Philadelphia) now suggest that even nonimmunogenic vectors such as adeno-associated virus (AAV) could trigger an immune reaction unless the expressed protein is under the control of a tissue-specific promoter (Hum. Gene Ther. 12, 205–215, 2001). Lee Sweeney and colleagues used a mouse model for muscular dystrophy to test the efficacy of two different AAV vectors containing the missing sarcoglycan (gsg) protein. Two promoters were used to control protein expression—a nonspecific cytomegalovirus (CMV) promoter and a muscle-specific creatine kinase (MCK) promoter. Animals injected with the CMV-based AAV vector generated antibodies against the muscle protein, whereas the MCK-based AAV vector elicited no such immune response. Though preliminary, the results indicate that tissue-specific promoters could circumvent dangerous immune reactions in patients undergoing trials of gene therapy for muscular dystrophy.