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Techniques and applications

Change of address for adenoviruses

Nature Reviews Microbiology volume 11, pages 224–225 (2013)Cite this article

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the bidirectional adapters not only allowed specific targeting of the desired cell type, but also reduced non-target binding

Binding of adenoviruses to their native cell receptor is mediated by the knob domain of the fibre capsid protein. Previous studies accomplished specific targeting of the most frequently used human adenovirus serotype, Ad5, using bidirectional adapter proteins in which one end binds to the knob domain and the other end binds to the desired cellular receptor. The authors had previously developed an adapter for a mutated Ad5 knob (Ad5 knob ΔTAYT; which lacks the ability to interact with the native Ad5 receptor) based on a fusion of two designed anykrin repeat proteins (DARPins). One of the DARPins was specific for human epidermal growth factor receptor 2 (HER2; also known as ERBB2), which is overexpressed in many tumour cells, and the second DARPin bound to the viral knob, although unstably. In this new study, the authors solved the crystal structure of the DARPin–Ad5 knob ΔTAYT complex to guide the design of a high-affinity adapter.

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ORIGINAL RESEARCH PAPER

  1. Dreier, B. et al. Development of a generic adenovirus delivery system based on structure-guided design of bispecific trimeric DARPin adapters. Proc. Natl Acad. Sci. USA 19 Feb 2013 (doi:10.1073/pnas.1213653110)

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  1. Ursula Hofer
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Hofer, U. Change of address for adenoviruses. Nat Rev Microbiol 11, 224–225 (2013). https://doi.org/10.1038/nrmicro3002

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