Therapeutic angiogenesis is a new potential treatment in cardiovascular disease. It is performed by the delivery of the angiogenic agents (protein, gene). Most important consideration for gene therapy is the construction of an effective therapeutic gene. Currently, VEGF is the most effective therapeutic gene for the neovascularization. We constructed the hypoxia-regulated VEGF plasmid using the Epo enhancer and RTP801 promoter. The efficiency of the pEpo-SV-VEGF and pRTP801-VEGF were evaluated by various methods in vitro and in vivo. The results suggested that the hypoxia-inducible VEGF gene therapy system is effective and safe, which may be useful for the gene therapy of ischemic heart disease. Development of a safe and efficient gene carrier is another main requirement for successful gene therapy. Although viral-based gene delivery is currently the most effective way to transfer genes to cells, nonviral vectors are increasingly being considered for in vivo gene delivery. The advantages of nonviral gene therapy are lack of specific immunogenecity, simplicity of use, and ease of large-scale production. In addition, the simple conjugation of a targeting moiety to nonviral gene carrier can facilitate tissue-targeting gene delivery. We have developed two new gene carrier systems, TerplexDNA and WSLP (water soluble lipopolymer). These two are efficient carrier to ischemic myocardium and has low toxicity and high transfection efficiency. So it may allow for application of in vivo gene therapy in the treatment of heart disease.