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Liver-Targeted Gene Delivery
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Recombinant Adeno-Associated Virus (rAAV) is a promising vector for gene therapy due to its capacity to confer long-term transgene expression in vivo and its theoretical safety profile. The recombinant viral DNA can be pseudotyped with different capsids (serotypes) which modify vector tropism and biology, extending the array of cell types and tissues which can be targeted efficiently with this vector system. There are more than 100 isolates of AAV, and 1 through to 11 have all been used in gene therapy. AAV8 pseudo-serotyped vectors have been shown to be highly efficient in gene delivery to both muscle and non-muscle tissues following systemic administration, in particular within the liver. We are interested in exploiting this to develop treatments for genetic disorders of the liver, in particular inborn errors of metabolism.
In some instances, liver transplantation is currently the only option for the long-term survival of affected children. However, this treatment has its own shortcomings. Delivery of therapeutic genes using rAAV may provide a safer and more effective alternative to liver transplantation. Liver-specific promoters can be used to restrict expression of the transgene to the hepatocytes, creating a highly specific gene delivery system. Using animal models, we are investigating the potential of AAV8-pseudotyped vectors to treat genetic liver disease with the ultimate aim of developing more effective treatments for children.
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