Author and year
Production system
Serotype
Transgene
Culture volume
Cell density (cells/mL)
VG/cell
VG/mL
IVP or TU/ cell
IVP or TU/mL
Cp/mL
Cp: VG: IVP or TU
Specific notes
Urabe et al[22]. (2002)
Three-Bac
2
GFP
200mL
2x106 a
4.5x104± 0.32x104 b
NA
NA
NA
NA
NA: 1344:1c ±283
First report of rAAV production in sf9 cells
Meghrous et al[48]. (2005)
Three-Bac
2
GFP
3L 20L 3.08x106 a 1.7x106 a
NA
NA
132 253 4.09x108 b d 4.46x108 b d 6.7x1011 b e 3.71x1011 b e 1640: NA: 1 830: NA: 1
Bac-Rep MOI optimization and demonstration of AAV production process scalability in bioreactor
Urabe et al [42]. (2006)
Three-Bac
5
hGFP
NA
NA
5.6x104± 0.32x104 f 7.67x104 ± 2.12x104 g
NA
NA
NA
NA
NA
Bac-Cap modification, VP1 Domain swapping to produce functional AAV5 vector particle
Aucoin et al[55]. (2006)
Three-Bac
2
GFP
20mL
NA
NA
2x1010 2x109
NA
5x107 d 1.7x108 d
NA
3400:400:1 3000:12:1 BacITR: BacRep: BacCap (1:9:1) BacITR: BacRep: BacCap (9:9:9)
Nagrete and Kotin[69] (2007)
Three-Bac
2
GFP
200mL 5L-Wave™ 20L-Wave™ 10L-STB 40L-STB
2x106 a
NA
~3x1010 b ~ 9x109 b ~5x109 b ~2x1010 b ~4.33x1010 b (±4.1x1010)
NA
~1x109 h ~5x108 h ~3x108 h ~5x108 h ~7.5x108 h (±2.5x108)
NA
NA: 30:1 NA: 18:1 NA: 16:1 NA: 40:1 NA: 20:1
Three-Bac system with a modified Bac-Cap sequence. Demonstration of AAV process scalability at large scale
Aucoin et al [68]. (2007)
Three-Bac
2
GFP
NA
NA
~12000
NA
200d
4x108
NA
4600:79:1
Temperature modulation study and its effect on AAV yield
Mena et al[59]. (2010)
Three-Bac
2
GFP
20mL 3L 9.43x106 i 9.5x106 i
NA
1.17x1011 b 2.2x1011 b
NA
2.9x109 b d (±0.32x109) 2.35x109 b d
NA
NA: 40:1 NA: 94:1
Low MOI, Fedbatch production
Liu et al [50]. (2010) Three-Bac 2 GFP 50mL 1x106 NA NA 240 2.4x108 NA NA AAV production in Sf21 cells in fed-batch culture
Cecchini et al[57]. (2011)
Three-Bac
9 8 6 GFP U7smOPT GFP U7smOPT PLS 10L 20L 100L 200L 20L 3.55x106 i 3.23x106 i 3.88x106 i 4.29x106 i (±1x106) 4.41x106 i 3.44x106 i 2.24x104 2.41x104 1.48x104 2x104 (±0.3x104) 1.82x104 2.07x104 7.9x1010 b 7.8x1010 b 4.44x1010 b 8.75x1010 b (±4.04x1010) 7.45x1010 b 5x1011 b
NA
NA
NA
NA
AAV production employing BIIC strategy. Demonstration of AAV production process robustness at bioreactor scale regardless of the type of transgene
Chen[33]. (2008)
Three-Bac Two Bac BacInRep/Cap 2 6 8 1 2 GFP GFP GFP GFP GFP
NA
5x106 a 5x106 a 5x106 a 5x106 a 5x106 a
NA
1.37x1011 b (±0.34x1011) 3.53x1010 b 9.65x1010 b 4.41x1010 b 2.2x1011
NA
NA
NA
NA
Bac-Intron constructs of baculovirus vector Baculovirus with enhanced passage dependent stability Bac-In-Rep/Cap and Bac-In-ITR
Smith et al. [34]. (2009)
Two-Bac BacRep2CapX 1 2 GFP GFP 200mL 200mL 2.4x106 a 1.2x106 a
NA
1.07x1013 j (±0.46x1013) 6.5x1012 j
NA
5.08x1010 j k (±5.9x1010) 1.9x1010 j k
NA
NA: 200:1 NA: 350:1
Bac-Rep/Cap and Bac-ITR based two baculovirus vectors with improved stability
Aslanidi et al[35]. (2009)
One-Bac 1.0
2 1 GFP GFP
NA
NA
1.4x105 7.3x104
NA
NA
NA
NA
NA
Inducible packaging Sf9 cell line for AAV production
Mietszch et al[39]. (2014)
One-Bac 1.0
1-11 12 GFP GFP
NA
NA
~104-105 l ~103 l
NA
NA
NA
NA
NA
Production of all AAV serotypes employing One-Bac system
Mietszch et al[45]. (2015) One-Bac 2.0 5 GFP NA NA 1x105 l NA NA NA NA NA One-Bac system with VP ratio restoration to improve AAV5 vector functionality
Joshi et al [58]. (2019)
One-Bac 3.0
5
GFP
25mL 3L 12x106 i 12x106 i 3x104± 0.4x104 2.7x104 2.7x1011 b (±0.37x1011) 3.8x1011 b (±0.53x1011) 20±5 22±5 1.9x108 b m (±0.43x108) 2.1x108 b m (±0.48x108)
ND
9600n: 2400:1 9400n: 2500:1
Robust, High MOI, Fedbatch AAV5 production process. Process validation at bioreactor scale. Improved volumetric yield of genomic and functional AAV5 vector
Yang et al [70]. (2019)
One-Bac 3.0+
2 8 9 GFP GFP GFP
NA
2x106 2x106 2x106 1.35x105 ±0.46x105 2.16x105 ±0.53x105 1.80x105 ±0.39x105
NA
NA
NA
NA
NA
One-Bac based Rep2 expressing transformed Sf9 cell line. Offer more flexibility for the production of multiple AAV serotypes production