Understanding capsid assembly and genome packaging for adeno-associated viruses

Adeno-associated viruses (AAVs) are promising therapeutic viral vectors. Their capsid is assembled from viral proteins VP1, VP2 and VP3, aided by an assembly-activating protein, followed by replication protein mediated packaging of their 4.7-kb genome with inverted terminal repeats as packaging signals. To aid improvement of AAV vectors, knowledge of viral determinants of successful capsid assembly and genome packaging is important. We review the current knowledge of these two processes and efforts to overcome limited DNA packaging capacity and limit the packaging of unwanted foreign DNA in vector development. Residues involved in essential capsid assembly and genome packaging interactions cannot be manipulated in vector engineering. This information thus aids strategies to improve vector production and to increase AAV packaging capacity toward improved efficacy of this vector system.