AAV Rep Proteins

From so simple beginnings…

Adeno-Associated Virus (AAV) is currently the most promising and successful gene therapy vector. It is been a long road since its discovery almost 50 years ago and its characterization as a defective parvovirus. Nevertheless, due to its lack of pathogenicity, limited immune host response and broad cell and tissue tropism, AAV fulfills many of the properties of an ideal gene therapy vector. Moreover, AAV is the only known eukaryotic virus that has evolved the property to integrate into its host genome site-specifically. The large AAV Rep proteins Rep68/Rep78 are the key players that carry out all processes required for AAV viability. Little is known about the molecular details of how AAV Rep proteins perform these functions and our research focuses on the structural and mechanistic determination of these processes using a combination of structural biology methods that include X-ray crystallography, small-angle X-ray scattering (SAXS) and single-particle reconstruction Cryo-EM.