Key result
Structural characterization of adeno-associated viruses enables the rational design of hybrid vectors with targeted tissue tropisms and the ability to escape neutralizing antibodies.
Understanding AAV structural biology allows for the rational design of hybrid vectors with targeted tissue tropisms and the ability to evade neutralizing antibodies.
May inform AAV vector optimization for cardiac gene therapy; leaves open validation in disease models and trials.
Adeno-associated viruses (AAVs) have become important therapeutic gene delivery vectors in recent years. However, there are challenges, including intractable tissues/cell types and pre-existing immune responses, which need to be overcome for full realization of this system. This review addresses strategies aimed at improving AAV efficacy in the clinic through the creation of hybrid vectors that display altered or more targeted specific tissue tropisms, while also escaping recognition from host-derived neutralizing antibodies. Characterization of these viruses with respect to serotypes contributing to their capsid, using available 3D structures, enables the identification of regions critical for particular tropism and antigenic phenotypes. Structural information also allows for rational design of vectors with specific targeted tropisms for improved therapeutic efficacy.
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Drouin et al. (2013) conducted a review in Gene therapy vector development. Adeno-Associated Virus (AAV) structural biology and hybrid vectors was evaluated. Structural characterization of adeno-associated viruses enables the rational design of hybrid vectors with targeted tissue tropisms and the ability to escape neutralizing antibodies.
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