2017
DOI: 10.1089/hgtb.2016.164
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OneBac 2.0:Sf9 Cell Lines for Production of AAV1, AAV2, and AAV8 Vectors with Minimal Encapsidation of Foreign DNA

Abstract: Recombinant adeno-associated viral (rAAV) vectors for human gene therapy require efficient and economical production methods to keep pace with the rapidly increasing clinical demand. In addition, the manufacturing process must ensure high vector quality and biological safety. The OneBac system offers easily scalable rAAV vector production in insect Sf9-derived AAV rep/cap-expressing producer cell lines infected with a single baculovirus that carries the rAAV backbone. For most AAV serotypes high burst sizes pe… Show more

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Cited by 29 publications
(24 citation statements)
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“…A further improvement has recently been shown whereby the rep/cap genes are stably integrated into the Sf9 cell line genome, but are under the control of a promoter/enhancer that is induced by subsequent baculovirus infection. In this system, infection can occur, with only one baculovirus containing the ITR-flanked gene of interest, simplifying the system significantly [ 86 , 87 ].…”
Section: Manufacturing For Clinical Usementioning
confidence: 99%
See 1 more Smart Citation
“…A further improvement has recently been shown whereby the rep/cap genes are stably integrated into the Sf9 cell line genome, but are under the control of a promoter/enhancer that is induced by subsequent baculovirus infection. In this system, infection can occur, with only one baculovirus containing the ITR-flanked gene of interest, simplifying the system significantly [ 86 , 87 ].…”
Section: Manufacturing For Clinical Usementioning
confidence: 99%
“…Concerns regarding baculovirus instability and differences in post-translational modifications between mammalian and insect cell systems are now beginning to be understood and controlled. These concerns are offset by the fact that baculovirus cannot efficiently infect mammalian cells which makes it inherently safer then other viral-based production systems [ 81 83 , 86 , 87 ].…”
Section: Manufacturing For Clinical Usementioning
confidence: 99%
“…Yields are typically quite high, with optimized processes producing approximately 10 10 -10 11 VG/ml on a 200L scale (Cecchini, Virag, & Kotin, 2011). Recently advances have simplified the system to the use of one baculovirus that expresses all necessary factors (Mietzsch et al, 2014(Mietzsch et al, , 2017.…”
Section: Aav Production By Baculovirus Expression Vector System (Bevs)mentioning
confidence: 99%
“…We used this SVN for high-throughput production and validation of an array of influenza VLPs with a large number of immune-modulating mutations in their hemagglutinin (HA) gene [47]. An unusual application of MultiBac technology involved the generation of recombinant adenovirus associated vector (rAAV) for gene therapy [48][49][50][51]. Here, MultiBac was used to provide all components (REP78, REP72, AAV virion coat proteins and the transgenes) required to co-produce gene-therapy-competent rAAVs in Sf9 insect cell cultures.…”
Section: Fluamentioning
confidence: 99%
“…Originally, this approach involved co-transfection of three individual MultiBac viruses to obtain intact rAAVs, constraining logistics. More recent refinement of the system, including integrating the encoding genes directly into the genome of the host Sf9 cells, resulting in a streamlined manufacturing process representing a viable alternative for rAAV production [48][49][50][51].…”
Section: Fluamentioning
confidence: 99%