Contrast variation studies of the structure of Adeno-associated viruses

Adeno-associated viruses (AAVs) are among the most promising viral vectors for gene therapy, with hundreds of ongoing clinical trials and six currently approved by the FDA as of August 2024. AAV virions consist of an icosahedral 25 nm capsid (diameter), composed of 60 viral proteins and packaging up to 4.7 kb of single-stranded DNA in the particle core. Despite their rapidly increasing commercial success, there remains a lack of understanding of product stability throughout manufacturing and long-term storage, with implications for their cost and availability. Our research aims to gain deeper insights into the colloidal stability of AAV vectors as well as the environmental conditions that trigger structural effects, such as aggregation and/or loss of the genome. Small-angle neutron scattering measurements at different contrasts access the effect of solution conditions on the full capsid structure, i.e., the protein outer shell and inner genome, playing a pivotal role in furthering our understanding of capsid morphologies and how they relate to the genome content at various conditions.