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Category: Japanese war journals Category: Bunka soldiers Category: Imperial Japanese Army Category: Japanese military journalsGene therapy has come a long way since the first gene therapy trials for patients with sickle cell disease in 1990. Some 100,000 patients are currently enrolled in clinical gene therapy trials in 90 countries. Patients with cancer, lysosomal storage diseases, and diverse metabolic disorders have benefited from these efforts. Gene therapy with AAV5 has become the standard of care in these trials, but the immune response limits the number of AAV5 doses that can be administered. AAV8, an alternative serotype that has a more favorable distribution, is emerging as a potential alternative. However, to date, the immune responses elicited by AAV8 remain largely undefined. Although AAV8 and AAV5 differ by up to 18%, both can efficiently transduce the liver, kidneys, and eyes, allowing intravenous administration in humans. [unreadable] [unreadable] In contrast to AAV5, which can transduce hepatocytes, the reticuloendothelial system (RES) is the dominant mechanism of AAV8 mediated transduction. Initial experiments in mice show that the magnitude of the immune response to an AAV8 vector is similar to that of the AAV5 vector. Transient expression elicits a neutralizing antibody response that is self-limited and does not significantly affect transgene expression. This phase I study will test the hypothesis that AAV8 vectors can be used to treat diseases characterized by a high demand for liver transduction, such as acute liver failure and hereditary tyrosinemia. The following aims will be examined: 1) Optimize the composition and envelope of recombinant AAV8 to achieve the highest level of hepatic transgene expression possible, 2) Optimize the administration route of AAV8 to achieve the highest level of liver transduction possible, and 3) Determine the efficacy of AAV8-mediated coagulopathy gene therapy for hereditary coagulopathy in a murine model. If the results of this study meet the goals of the proposed studies, the applicant will be eligible to submit an NIH RO1 application for further development and testing of AAV8 based therapies in a phase II study.Q: Moment js not formatting time correctly I want to format a date in my chrome console and it not working. Moment format a date: moment(new Date()).format c6a93da74d


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