Adenoviral Expression of Suppressor of Cytokine Signaling-1 Reduces Adenovirus Vector-Induced Innate Immune Responses

摘要: Adenovirus (Ad) vectors are among the most commonly used viral in gene therapy clinical trials. However, application of Ad has been limited to local injection many cases, because systemic administration triggers innate immune responses such as inflammatory cytokine production and tissue damage. To overcome this limitation, it will be necessary develop safer less likely induce response. In present study, we demonstrated that a suppressor signaling-1 (SOCS1)-expressing vector, Ad-SOCS1, reduces response induced by vectors. RAW264.7-SOCS1, macrophage-like cell line stably expresses SOCS1, was shown produce lower levels cytokines after transduction The Ad-SOCS1 into mice elicited reduced cytokines, compared with control vectors, i.e., luciferase-expressing Ad-L2. Furthermore, coadministration Ad-L2 attenuated liver toxicity alone, achieved without suppression luciferase various organs. JAK/STAT pathway involved vector-mediated production, which impaired overexpression SOCS1. These findings indicate could useful for reducing immunity.