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. hand, as with retroviral vectors, the viral envelope protein plays an essential role in the efficacy of the method.
In our view, the ideal strategy for gene therapy of this type of disease is passive immunization by gene therapy. We have previously demonstrated that active immunization against PrP^Sc^ clears the brain of infectivity. Recently, adoptive immunization against PrP^Sc^ has been achieved by transgenic expression of PrP^C^ in the CNS and peripheral lymphoid tissues. However, this approach requires a long-term expression of PrP^C^. Our vector provides a direct strategy of using immunotherapy to treat prion infection.
In summary, this study provides a proof of concept demonstrating the treatment of scrapie-infected mice by direct intracerebral inoculation of PrP^C^-expressing adeno-associated viral vectors. Our results encourage further study of this therapeutic approach in larger animal models of prion disease. It is notable that this therapeutic method relies on the ability of the viral envelope protein to allow entry of the viral vector into the CNS. Although the use of an immunotoxic viral envelope protein may provide an effective approach to safely treat prion infection and other CNS diseases, it remains to be determined whether an effective, non-immunotoxic envelope protein exists. Thus, the use of adeno-associated viral vectors with native envelope proteins is a promising new strategy for gene therapy of CNS diseases.
The authors would like to thank Dr. Eline Hackman and Dr. Phyllis Gale for their kind
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