The present invention relates to methods for modulating, i.e., agonizing or antagonizing, Stat3 (Signal Transducer and Activator of Transcription3) signaling activity for use in gene therapy. Inhibition and/or activation of Stat3 signaling is an effective approach to modulate angiogenesis and the immune response for treatment and/or prevention of inflammation, infection, inflammation, immune disorders, and ischemia.