Gene therapy has emerged as a novel therapy to promote angiogenesis in patients with critical limb ischemia (CLI) caused by peripheral artery disease. We focused on hepatocyte growth factor (HGF) as pro-angiogenic factors. In phase III clinical trial, naked plasmid DNA encoding HGF showed the safety and their potential for symptomatic improvement in CLI patients. Based on phase III data, HGF gene therapy drug, Collategene, has been approved by PMDA in Japan. Collategene was launched in Japan market as the first gene therapy drug at 2019. In this session, we would like to discuss about future application of HGF gene therapy.
　　In addition, we recently focused on the therapeutic vaccination which has extended its scope from infectious diseases to chronic diseases. We reported that angiotensin (Ang) II vaccine for hypertension successfully attenuated the high blood pressure in animal models (PLoS One 2013, Sci Rep 2017, Stroke 2017). Increasing the effectiveness of drug adherence interventions may have a great impact on the health of the population, because approximately 50% may not take medications. This poor adherence to medication leads to increased morbidity and death. As a result, the vaccine-induced anti-Ang II antibodies can efficiently ameliorate Ang II-induced high blood pressure and perivascular fibrosis in mice. Phase I/II clinical trial demonstrated good safety profile and the production of antibody against Ang II. In next step, we will start phase IIb study to test the anti-hypertensive efficacy.
　　Based on plasmid DNA platform technology, we have applied to develop DNA vaccine against COVID-19. Successfully, we have developed DNA vaccine against SARS-Cov2. Now, phase II/III clinical trial using our DNA vaccine was already started, from 4Q on 2020. In addition, AnGes has started another phase 1/2 study to increase the efficacy. As the safety profile of DNA vaccine was very well, in this lecture, I would like to discuss about DNA vaccine against COVID-19.