Understanding Capsid Assembly and Genome Packaging for Adeno-Associated Viruses

Abstract

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.

KEYWORDS :

• adeno-associated virus
• assembly
• capsid
• gene therapy
• oversized vectors packaging
• replication
• self-complementary vectors

Financial & competing interests disclosure

This work was supported by NIH grants R01 GM109524 and R01 GM082946. M Agbandje-McKenna is an SAB member for Voyager Therapeutics, Inc., and has a sponsored research agreement with AGTC, Adverum Biotechnologies, and Voyager Therapeutics. She is a consultant for Intima Biosciences. These companies have interest in the development of AAV for gene delivery applications. M Agbandje-McKenna and M Mietzsch are inventors of AAV patents licensed to various biopharmaceutical companies. M Agbandje-McKenna is a cofounder of StrideBio Therapeutics, LLC. This is a biopharmaceutical company with interest in developing AAV vectors for gene delivery application. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.