Manufacturing and characterizing AAV-based vectors for use in clinical studies
Abstract
Recombinant adeno-associated virus (AAV)-based vectors expressing therapeutic gene products have shown great promise for human gene therapy. A major challenge for translation of promising research to clinical development is the manufacture and certification of AAV vectors for clinical use. This review summarizes relevant aspects of current Good Manufacturing Practice, focusing on considerations and challenges specific for recombinant AAV.
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Reverse packaging results in the packaging of DNA sequences outside of the ITR-flanked vector genome cassette.
“Third, a phenomenon termed ‘reverse packaging’ has been described that results in the packaging of DNA sequences outside of the ITR-flanked vector genome cassette [84].”
From Understanding Capsid Assembly and Genome Packaging for Adeno-Associated Viruses (2017) · cites this paper as [84]
The choice of production platform and the size of the plasmid affect the extent to which reverse packaging of non-transgene sequences leads to generation of an undesirable subpopulation of capsids partially filled with DNA impurities.
“In addition, the choice of production platform and the size of the plasmid affect the extent to which reverse packaging of non-transgene sequences leads to the generation of an undesirable subpopulation of capsids partially filled with DNA impurities.40,41”
From Analytical methods for process and product characterization of recombinant adeno-associated virus-based gene therapies (2021) · cites this paper as [41]
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- Authors
- Wright, J. F.
- Affiliations
- Children's Hospital of Philadelphia (US)
- Corresponding author
- Wright, J F
- ORCID
- Wright, J F
- Venue
- Gene Therapy
- Published
- 2008-04-17
- Volume
- 15
- Issue
- 11
- Pages
- 840-848
- ISSN
- 0969-7128 (ISSN-L)
- 1476-5462
- OpenAlex
- W2048382073
- Cited by
- 205
- References
- 50
- Citations by year
- 2026: 12 · 2025: 15 · 2024: 25 · 2023: 18 · 2022: 13 · 2021: 26 · 2020: 12 · 2019: 12 · 2018: 9 · 2017: 14 · 2016: 7 · 2015: 6 · 2014: 4 · 2013: 6 · 2012: 7
- FWCI
- 0.59
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Gene Therapy (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Viral Infectious Diseases and Gene Expression in Insects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- recombinant adeno-associated virus vectors, current good manufacturing practice, clinical translation, gene therapy vectors
- MeSH terms
- Dependovirus, Genetic Engineering, Genetic Vectors, Humans, Industry, Quality Control, Recombinant Proteins, Genetic Therapy
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