GFP Adeno-Associated Virus ( AAV-VTAGRAP )

Most isolated AAV serotypes and other natural variants reported to date exhibit broad nonspecific transduction profiles with a bias toward the liver and spleen upon systemic administration. However, it is worth mentioning that the route of administration also plays a key role in determining the tropism of the vector, followed by the properties of the capsid. Therefore, the chosen vector should be selected and optimized based on the tissue or cell target of interest and the route of application, as well as other considerations such as the anti-AAV immune status of the patient. For systemic applications, effective targeting often requires engineering to allow adequate vector homing to the intended target cells. Various strategies have been employed to alter the properties of the AAV capsid, including modifying its intrinsic tropism. These strategies can be roughly divided into (i) rational design of modified capsid structures and (ii) random modification combined with directed evolution to enrich for capsid variants with desired characteristics. Regardless of the approach, there is always the possibility that changes in the AAV capsid sequence and structure will not only alter the transduction properties of the engineered capsid, but also affect its ability to assemble and package the viral genome. Since these parameters critically determine the ultimate suitability of synthetic AAV capsids for use in human patients, they must be carefully monitored during the capsid engineering process, and libraries should be optimized for viability (so-called “smart libraries”) rather than pure complexity.