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- W2010805983 abstract "We have generated a panel of metabolically biotinylated adenoviral vectors based on the genetic insertion of a biotin acceptor peptide (BAP) into the fiber, protein IX, and hexon capsomers of the Ad5 virion. Here we demonstrate that avidin-based redirection of Ad transduction through biotinylated ligand:receptor interactions is greatly dependent on the nature of the BAP-modified capsomer. While transduction of Ad-Fiber-BAP can generally be targeted through a wide range of ligand:receptor pairs, Ad-IX-BAP and Ad-Hexon-BAP are surprisingly inefficient as targeting platforms, despite having a higher display of biotins than Ad-Fiber-BAP. We reason this difference is due to the nature of the interactions between viral capsomers and cell surface receptors. Ad5 fiber, the natural cell-binding capsomer, has evolved to bind very tightly to cell surface CAR. Upon endosomal uptake fibers then dissociate from the capsid, releasing the virion from the receptor and enabling trafficking to continue. We believe that targeting Ad through IX or hexon capsomers results in the entrapment of virions on cellular receptors thereby leading to very inefficient transduction. Indeed, preliminary evidence suggests that protein IX stays tightly associated with the virion and does not dissociate at early stages of vector trafficking like fiber. We reason that targeted transduction through IX or hexon may be feasible with ligands that naturally release from their receptors upon endocytosis, resulting in release of the incoming virions. These initial results highlight the importance of knowledge of capsomer, ligand, and receptor biology when engineering new tropism into viral capsids and may be of great importance for vectors like AAV, which do not shed capsomers as they traffic. Current progress on the analysis of the differences in trafficking between the different BAP-modified vectors will be presented." @default.
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- W2010805983 date "2005-05-01" @default.
- W2010805983 modified "2023-09-27" @default.
- W2010805983 title "29. Redirection of Adenoviral Tropism through Capsomers Other Than Fiber Is Generally Inefficient and Dependent on Ligand-Receptor Biology" @default.
- W2010805983 doi "https://doi.org/10.1016/j.ymthe.2005.06.031" @default.
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