Skip to Main content Skip to Navigation
Journal articles

Pharmacology of Recombinant Adeno-associated Virus Production

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.
Document type :
Journal articles
Complete list of metadatas

Cited literature [133 references]  Display  Hide  Download

https://www.hal.inserm.fr/inserm-01735009
Contributor : Nicolas Jaulin <>
Submitted on : Thursday, March 15, 2018 - 12:53:57 PM
Last modification on : Friday, July 10, 2020 - 2:08:05 PM
Long-term archiving on: : Tuesday, September 11, 2018 - 12:14:12 AM

File

1-s2.0-S2329050118300032-main....
Publication funded by an institution

Identifiers

Collections

Citation

Magalie Penaud-Budloo, Achille François, Nathalie Clément, Eduard Ayuso. Pharmacology of Recombinant Adeno-associated Virus Production. Molecular Therapy - Methods and Clinical Development, Nature Publishing Group, 2018, 8, pp.166 - 180. ⟨10.1016/j.omtm.2018.01.002⟩. ⟨inserm-01735009⟩

Share

Metrics

Record views

230

Files downloads

2262