Optimization of gene transfer conditions to adipose tissue and application toward hemophilia

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Adipose tissue is potentially a suitable target of gene transfer for diseases like hemophilia. However, no efficient method has been developed for in vivo gene transfer. In this study, we explored the utility of excipients to augment gene transfer into the adipose tissue of mice and found that Pluronic F88 was useful for this purpose when combined with AAV serotype 1 vectors. The improvement was also demonstrated by vectors encoding murine erythropoietin, and the mice became polycythemic. Moreover, after removing transduced adipose tissue, plasma erythropoietin levels returned to normal, which suggests the unique advantage of this method. When AAV8-based vector was tested in the same manner, robust transgene expression was observed in the liver rather than the injected adipose tissue. This finding led to the discovery of ectopic liver expression following intramuscular injection of AAV8-based vectors. On the other hand, in experiments with vectors encoding coagulation factor IX gene, transgene expression level was not satisfactory in mice. The reason for this phenomenon is still unclear and need to be clarified in the future. Further optimization and analysis is necessary to improve the level of transgene expression and application to the diseases other than hemophilia.