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Coagulation factor X (FX) -binding adenovirus 5 (Ad5) for systemic gene delivery

Cell culture and mouse studies suggest FX binding by Ad5 is required for efficient gene therapy with the vector. Prior studies showed that FX increases liver tropism for Ad5 and suggested that engineered viruses lacking FX binding could be useful for systemic gene therapy. In cultured cells incubated in serum, an Ad5 vector engineered to not bind FX had decreased transduction efficiency compared with an FX-binding control vector. In mice lacking antibodies or components of the complement system, the non-FX-binding Ad5 vector had comparable efficiency to an FX-binding Ad5 vector, suggesting that FX helps prevent neutralization of the vector by the complement system. Next steps include exploring how other adenovirus serotypes interact with the complement system.

SciBX 6(13); doi:10.1038/scibx.2013.320
Published online April 4, 2013

Unpatented; licensing status not applicable

Xu, Z. et al. Nat. Med.;
published online March 24, 2013;
Contact: Andrew P. Byrnes, Food and Drug Administration, Bethesda, Md.