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Cachexia is associated with life-threatening diseases, such as cancer and AIDS, especially gastrointestinal tract and lung cancer, where it contributes to the morbidity and mortality caused by these systemiccancers. NF-κB, a heterodimeric transcription factor, is involved in the impaired balance of protein synthesis and degradation, which characterizes cancer-induced cachexia. We have previously shown in an in vitro model using primary muscle cells, that exposure to conditioned media from certain carcinoma cell lines results in failure of myotube formation, providing an in vitro correlate of cancer cachexia. In the in vitro studies, stable transduction of IkB super- repressor (IkBSR) reversed the failure of myotube formation induced by cancer cell media. We demonstrated that the mechanism of effect of IkBSR was through prevention of NF-kB activation in muscle cells. In this study we chose to examine whether adeno-associated virus serotype one (AAV1) carrying the IkBSR expression cassete (AAV1-IKBSR) could block NF-κB activation and subsequently alleviate the findings associated with cancer cachexia in skeletal muscle tissue in vivo. BALB/c nude mice were injected with prostate cancer 3 (PC3) cells and demonstrated symptoms associated with cancer cachexia such as reduced skeletal muscle weight and an increase in the degradation rate of muscle proteins, such as myosin heavy chain. This effect correlated with an increase of NF-kB translocation into the nucleus thus generating an in vivo cachexia model. We have cloned and rescued an AAV1 vector carrying an IkBSR expression cassette. This vector will be used in the in vivo model of cancer cachexia toward the prevention or treatment of cancer cachexia.Molecular Therapy (2006) 13, S221–S221; doi: 10.1016/j.ymthe.2006.08.647 [ABSTRACT FROM AUTHOR]