Matches in SemOpenAlex for { <https://semopenalex.org/work/W2918328056> ?p ?o ?g. }
- W2918328056 abstract "Abstract AAV vectors poorly transduce Dendritic cells (DC), a feature invoked to explain AAV’s low immunogenicity. However, the reason for this non-permissiveness remained elusive. Here, we performed an in-depth analysis using human monocyte-derived immature DC (iDC) as model. iDC internalized AAV vectors of various serotypes, but even the most efficient serotype failed to transduce iDC above background. Since AAV vectors reached the cell nucleus, we hypothesized that AAV’s intracellular processing occurs suboptimal. On this basis, we screened an AAV peptide display library for capsid variants more suitable for DC transduction and identified the I/VSS family which transduced DC with efficiencies of up to 38%. This property correlated with an improved vector uncoating. To determine the consequence of this novel feature for AAV’s in vivo performance, we engineered one of the lead candidates to express a cytoplasmic form of ovalbumin, a highly immunogenic model antigen, and assayed transduction efficiency as well as immunogenicity. The capsid variant clearly outperformed the parental serotype in muscle transduction and in inducing antigen-specific humoral and T cell responses as well as anti-capsid CD8 + T cells. Hence, vector uncoating represents a major barrier hampering AAV vector-mediated transduction of DC and impacts on its use as vaccine platform." @default.
- W2918328056 created "2019-03-11" @default.
- W2918328056 creator A5014745527 @default.
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- W2918328056 date "2019-03-06" @default.
- W2918328056 modified "2023-10-18" @default.
- W2918328056 title "Vector uncoating limits adeno-associated viral vector-mediated transduction of human dendritic cells and vector immunogenicity" @default.
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- W2918328056 doi "https://doi.org/10.1038/s41598-019-40071-1" @default.
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