Pharmacology of Recombinant Adeno-associated Virus Production

Penaud-Budloo, Magalie; François, Achille; Clément, Nathalie; Ayuso, Eduard

doi:10.1016/j.omtm.2018.01.002

Cited by 177Virus-based gene therapy researchViral Infectious Diseases and Gene Expression in InsectsRNA Interference and Gene Delivery

Pharmacology of Recombinant Adeno-associated Virus Production

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Penaud-Budloo, Magalie, François, Achille, Clément, Nathalie, Ayuso, Eduard·2018·Molecular Therapy - Methods & Clinical Development

DOI 10.1016/j.omtm.2018.01.002PMC PMC5908265

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Abstract

Recombinant adeno-associated viral (rAAV) vectors have been used in more than 150 clinical trials with a good safety profile and significant clinical benefit in many genetic diseases. In addition, due to their ability to infect non-dividing and dividing cells and to serve as efficient substrate for homologous recombination, rAAVs are being used as a tool for gene-editing approaches. However, manufacturing of these vectors at high quantities and fulfilling current good manufacturing practices (GMP) is still a challenge, and several technological platforms are competing for this niche. Herein, we will describe the most commonly used upstream methods to produce rAAVs, paying particular attention to the starting materials (input) used in each platform and which related impurities can be expected in final products (output). The most commonly found impurities in rAAV stocks include defective particles (i.e., AAV capsids that do contain the therapeutic gene or are not infectious), residual proteins from host cells and helper viruses (adenovirus, herpes simplex virus, or baculoviruses), and illegitimate DNA from plasmids, cells, or helper viruses that may be encapsidated into rAAV particles. Given the role that impurities may play in immunotoxicity, this article reviews the impurities inherently associated with each manufacturing platform.

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Different factors, such as the length and type of the vector genome, contribute to variability in the overall ratio of capsids without the intended vector genome.
“Different factors, such as the length and type of the vector genome (i.e., single stranded or self-complementary), contribute to the variability in the overall ratio of capsids without the intended vector genome.19,29”
From Analytical methods for process and product characterization of recombinant adeno-associated virus-based gene therapies (2021) · cites this paper as [29]
The ratio of full capsids to all capsids, the content ratio, can vary from less than 1% to 30% in the production culture at the time of harvest and is inconsistent between production runs.
“The ratio of full capsids to all capsids, termed content ratio, can vary from <1% to 30% in the production culture at the time of harvest and is inconsistent between production runs (Figure 1).6,28, 29, 30”
From Analytical methods for process and product characterization of recombinant adeno-associated virus-based gene therapies (2021) · cites this paper as [29]

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[10]Thakur, S.S. (2012). Production of recombinant adeno-associated viral vectors in yeast. MS thesis (Gainesville, FL: University of Florida). http://ufdc.ufl.edu/UFE0044702/00001.

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Recombinant Adeno-Associated Virus (rAAV) Manufacturing Platforms: Process and Quality Considerations
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Authors: Penaud-Budloo, M., François, A., Clément, N., & Ayuso, E.
Affiliations: Inserm (FR)
University of Florida (US)
Corresponding author: Ayuso, Eduard
ORCID: François, Achille
Ayuso, Eduard
Venue: Molecular Therapy - Methods & Clinical Development
Publisher: Elsevier BV
Published: 2018-03
Volume: 8
Pages: 166-180
ISSN: 2329-0501 (ISSN-L)
DOI: 10.1016/j.omtm.2018.01.002
PMC: PMC5908265
OpenAlex: W2782944478
Cited by: 177
References: 136
Citations by year: 2026: 13 · 2025: 15 · 2024: 24 · 2023: 31 · 2022: 17 · 2021: 35 · 2020: 22 · 2019: 13 · 2018: 7
FWCI: 2.69
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by-nc-nd
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
creativecommons.org/licenses/by-nc-nd/4.0/ (vor)
Locations: Molecular Therapy — Methods & Clinical Development (publishedVersion, cc-by-nc-nd)
Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
PubMed Central (publishedVersion, cc-by-nc-nd)
PubMed (publishedVersion)
HAL (submittedVersion, other-oa)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders: INSERM
University of Nantes
CHU of Nantes
Fondation d’Entreprises pour la Thérapie Génique en Pays de la Loire
Région Pays de la Loire and Pre-industrial gene therapy consortium
Agence Nationale de la Recherche-investissements d’avenir (10-DPBS-0001)
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, AAV vector production, gene therapy manufacturing, helper virus, immunotoxicity, current good manufacturing practice

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Pharmacology of Recombinant Adeno-associated Virus Production

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