Development of a generic adenovirus delivery system based on structure-guided design of bispecific trimeric DARPin adapters.

ABSTRACT: Adenoviruses (Ads) have shown promise as vectors for gene delivery in clinical trials. Efficient viral targeting to a tissue of choice requires both ablation of the virus' original tropism and engineering of an efficient receptor-mediated uptake by a specific cell population. We have developed a series of adapters binding to the virus with such high affinity that they remain fully bound for >10 d, block its natural receptor binding site and mediate interaction with a surface receptor of choice. The adapter contains two fused modules, both consisting of designed ankyrin repeat proteins (DARPins), one binding to the fiber knob of adenovirus serotype 5 and the other binding to various tumor markers. By solving the crystal structure of the complex of the trimeric knob with three bound DARPins

SUBMITTER: Dreier B 

PROVIDER: S-EPMC3593905 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature