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• W2093450168 abstract "The use of adeno-associated viral (AAV) vectors for gene replacement therapy is currently being explored in several clinical indications. However, reports have suggested that input capsid proteins from AAV-2 vector particles may result in the stimulation of cytotoxic T lymphocyte (CTL) responses that can result in a loss of transduced cells. To explore the impact of anti-AAV CTLs on AAV-mediated transgene expression, both immunocompetent C57BL/6 mice and B cell-deficient μMT mice were immunized against the AAV2 capsid protein (Cap) and were injected intravenously with an AAV-2 vector encoding α-galactosidase (α-Gal). C57BL/6 mice, which developed both CTL and neutralizing antibody responses against Cap, failed to show any detectable α-Gal expression. In contrast, serum α-Gal levels comparable to those of naive mice were observed in μMT mice despite the presence of robust CTL activity against Cap, indicating that preexisting Cap-specific CTLs did not have any effect on the magnitude and duration of transgene expression. The same strategy was used to assess the impact of CTLs against the α-Gal transgene product on AAV-mediated gene delivery and persistence of transgene expression. Preimmunization of μMT mice with an Ad/α-Gal vector induced a robust CTL response to α-Gal. When these mice were injected with AAV2/α-Gal vector, initial levels of α-Gal expression were reduced by more than 1 log and became undetectable by 2 weeks postinjection. Overall, our results indicate that CTLs against the transgene product as opposed to AAV capsid protein are more likely to interfere with AAV transgene expression." @default.
• W2093450168 created "2016-06-24" @default.
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• W2093450168 date "2009-01-01" @default.
• W2093450168 modified "2023-10-17" @default.
• W2093450168 title "Cytotoxic T Lymphocyte Responses to Transgene Product, Not Adeno-Associated Viral Capsid Protein, Limit Transgene Expression in Mice" @default.
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• W2093450168 doi "https://doi.org/10.1089/hum.2008.055" @default.
• W2093450168 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2855252" @default.
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• W2093450168 hasPublicationYear "2009" @default.
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