Understanding capsid assembly and genome packaging for adeno-associated viruses
Antonette Bennett1, Mario Mietzsch1, Mavis Agbandje-McKenna1
1Department of Biochemistry & Molecular Biology, Center for Structure Biology, McKnight Brain Institute, University of Florida, Gainesville, FL 32610-0245, USA.
Future Virology
|February 13, 2023
Summary
Adeno-associated virus (AAV) vector engineering requires understanding capsid assembly and genome packaging. Knowledge of these viral processes aids strategies to improve AAV vector production and packaging capacity for enhanced therapeutic efficacy.
Area of Science:
- Molecular Biology
- Virology
- Gene Therapy
Background:
- Adeno-associated viruses (AAVs) are critical viral vectors for gene therapy.
- AAV capsid assembly involves viral proteins (VP1, VP2, VP3) and an assembly-activating protein.
- Genome packaging relies on replication proteins and specific packaging signals within the viral genome.
Purpose of the Study:
- To review current knowledge on AAV capsid assembly and genome packaging determinants.
- To discuss strategies for overcoming limitations in AAV DNA packaging capacity.
- To address the challenge of preventing the packaging of foreign DNA in AAV vectors.
Main Methods:
- Literature review of existing research on AAV structure and function.
- Analysis of viral protein interactions critical for capsid formation.
- Examination of mechanisms governing AAV genome packaging.
Main Results:
- Essential residues for capsid assembly and genome packaging interactions are not amenable to modification in vector engineering.
- Understanding these interactions is key to improving AAV vector production.
- Strategies exist to enhance AAV packaging capacity and minimize unwanted DNA packaging.
Conclusions:
- Knowledge of AAV capsid assembly and genome packaging is crucial for advancing AAV vector technology.
- Further research can optimize AAV vector production and efficacy.
- This understanding supports the development of safer and more effective gene therapies using AAV vectors.
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