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Monobac System–A Single Baculovirus for the Production of rAAV

Large-scale manufacturing of rAAV is a bottleneck for the development of genetic disease treatments. The baculovirus/Sf9 cell system underpins the first rAAV treatment approved by EMA and remains one of the most advanced platforms for rAAV manufacturing. Despite early successes, rAAV is still a comp...

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Autores principales: Galibert, Lionel, Jacob, Aurélien, Savy, Adrien, Dickx, Yohann, Bonnin, Delphine, Lecomte, Christophe, Rivollet, Lise, Sanatine, Peggy, Boutin Fontaine, Marjorie, Le Bec, Christine, Merten, Otto-Wilhelm
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8465638/
https://www.ncbi.nlm.nih.gov/pubmed/34576695
http://dx.doi.org/10.3390/microorganisms9091799
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author Galibert, Lionel
Jacob, Aurélien
Savy, Adrien
Dickx, Yohann
Bonnin, Delphine
Lecomte, Christophe
Rivollet, Lise
Sanatine, Peggy
Boutin Fontaine, Marjorie
Le Bec, Christine
Merten, Otto-Wilhelm
author_facet Galibert, Lionel
Jacob, Aurélien
Savy, Adrien
Dickx, Yohann
Bonnin, Delphine
Lecomte, Christophe
Rivollet, Lise
Sanatine, Peggy
Boutin Fontaine, Marjorie
Le Bec, Christine
Merten, Otto-Wilhelm
author_sort Galibert, Lionel
collection PubMed
description Large-scale manufacturing of rAAV is a bottleneck for the development of genetic disease treatments. The baculovirus/Sf9 cell system underpins the first rAAV treatment approved by EMA and remains one of the most advanced platforms for rAAV manufacturing. Despite early successes, rAAV is still a complex biomaterial to produce. Efficient production of the recombinant viral vector requires that AAV replicase and capsid genes be co-located with the recombinant AAV genome. Here, we present the Monobac system, a singular, modified baculovirus genome that contains all of these functions. To assess the relative yields between the dual baculovirus and Monobac systems, we prepared each system with a transgene encoding γSGC and evaluated vectors’ potency in vivo. Our results show that rAAV production using the Monobac system not only yields higher titers of rAAV vector but also a lower amount of DNA contamination from baculovirus.
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spelling pubmed-84656382021-09-27 Monobac System–A Single Baculovirus for the Production of rAAV Galibert, Lionel Jacob, Aurélien Savy, Adrien Dickx, Yohann Bonnin, Delphine Lecomte, Christophe Rivollet, Lise Sanatine, Peggy Boutin Fontaine, Marjorie Le Bec, Christine Merten, Otto-Wilhelm Microorganisms Article Large-scale manufacturing of rAAV is a bottleneck for the development of genetic disease treatments. The baculovirus/Sf9 cell system underpins the first rAAV treatment approved by EMA and remains one of the most advanced platforms for rAAV manufacturing. Despite early successes, rAAV is still a complex biomaterial to produce. Efficient production of the recombinant viral vector requires that AAV replicase and capsid genes be co-located with the recombinant AAV genome. Here, we present the Monobac system, a singular, modified baculovirus genome that contains all of these functions. To assess the relative yields between the dual baculovirus and Monobac systems, we prepared each system with a transgene encoding γSGC and evaluated vectors’ potency in vivo. Our results show that rAAV production using the Monobac system not only yields higher titers of rAAV vector but also a lower amount of DNA contamination from baculovirus. MDPI 2021-08-24 /pmc/articles/PMC8465638/ /pubmed/34576695 http://dx.doi.org/10.3390/microorganisms9091799 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Galibert, Lionel
Jacob, Aurélien
Savy, Adrien
Dickx, Yohann
Bonnin, Delphine
Lecomte, Christophe
Rivollet, Lise
Sanatine, Peggy
Boutin Fontaine, Marjorie
Le Bec, Christine
Merten, Otto-Wilhelm
Monobac System–A Single Baculovirus for the Production of rAAV
title Monobac System–A Single Baculovirus for the Production of rAAV
title_full Monobac System–A Single Baculovirus for the Production of rAAV
title_fullStr Monobac System–A Single Baculovirus for the Production of rAAV
title_full_unstemmed Monobac System–A Single Baculovirus for the Production of rAAV
title_short Monobac System–A Single Baculovirus for the Production of rAAV
title_sort monobac system–a single baculovirus for the production of raav
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8465638/
https://www.ncbi.nlm.nih.gov/pubmed/34576695
http://dx.doi.org/10.3390/microorganisms9091799
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