Adeno-Associated Virus (AAV) Engineering for Enhanced Specificity of Disease-Targeted Viral Gene Vectors

Adeno-associated virus (AAV) is under intense investigation as a potential clinical therapeutic gene delivery vector. Virus targeting is a widely investigated endeavor, and much progress has been made through the use of specific ligand-receptor interactions. Using X-ray crystallography data for AAV2 as a structural guide, vector targeting has been achieved through rational design. Directed evolution, on the other hand, has been used as an alternative platform for creating novel AAV vectors, where detailed a priori knowledge of intricate ligand-receptor interactions is unnecessary. Through a combination of rational design and directed evolution approaches, we attempt to expand traditional virus targeting methods to create novel AAV gene delivery vectors with enhanced specificity.