抄録 |
AAV (adeno-associated virus) vectors are considered to be promising gene-delivery vehicles for gene therapy, because they are derived from non-pathogenic virus, efficiently transduce non-dividing cells, and cause long-term transgene expression. Appropriate AAV serotypes are utilized depending on the type of target cells; e.g., neurons are efficiently transduced with AAV2 vector, and AAV8 vector is most efficient for hepatocytes. Among various target diseases for AAV vector-mediated gene therapy, Parkinson's disease is one of the most promising candidates. AAV vector-mediated AADC (aromatic L-amino acid decarboxylase; the enzyme converting L-DOPA to DA) gene transfer in combination with oral administration of L-DOPA has been shown to be efficacious in clinical trials. AAV vectors may be suitable for gene therapy of hemophilia. For the liver-mediated transduction, intravenous injection of AAV8 vector seems practical. In such an approach, inhibitory actions of pre-existing neutralizing antibody (NAb) against vector capsids should be eliminated. We demonstrated the efficacy of intravascular saline flushing before and after vector injection in order to avoid contact of vectors with neutralizing antibodies. This study was performed in collaboration with Division of Neurology and Division of Cell and Molecular Medicine, Jichi Medical University; Tsukuba Primate Research Center, National Institute for Biomedical Innovation; and The Corporation for Production and Research of Laboratory Primates, Japan. |