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55. Yu Y, Liao L, Shao B et al (2017) Knockdown
of microRNA let-7a improves the functionality of bone marrow-derived mesenchymal
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ymthe.2016.11.015
56. Huang B, Jiang X-C, Zhang T-Y et al (2017)
Peptide modified mesenchymal stem cells as
targeting delivery system transfected with
miR-133b for the treatment of cerebral ischemia. Int J Pharm 531(1):90–100. https://
doi.org/10.1016/j.ijpharm.2017.08.073
57. Balmayor ER, Geiger JP, Koch C et al (2017)
Modified mRNA for BMP-2 in combination
with biomaterials serves as a transcriptactivated matrix for effectively inducing osteogenic pathways in stem cells. Stem Cells Dev
26(1):25–34. https://doi.org/10.1089/scd.
2016.0171
58. Sprick G, Weidner T, Salzig D et al (2017)
Baculovirus-induced recombinant protein
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1016/j.nbt.2017.08.006
59. Brooks AR, Harkins RN, Wang P et al (2004)
Transcriptional silencing is associated with
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following adenoviral gene delivery to muscle.
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10.1002/jgm.516
60. Meilinger D, Fellinger K, Bultmann S et al
(2009) Np95 interacts with de novo DNA
methyltransferases, Dnmt3a and Dnmt3b,
and mediates epigenetic silencing of the viral
CMV promoter in embryonic stem cells.
EMBO Rep 10(11):1259–1264. https://
doi.org/10.1038/embor.2009.201
61. Wang J, Zhu L, Chen X et al (2019) Human
bone marrow mesenchymal stem cells functionalized by hybrid baculovirus-adeno-associated
viral
vectors
for
targeting
hypopharyngeal carcinoma. Stem Cells Dev
28(8):543–553. https://doi.org/10.1089/
scd.2018.0252
62. Contreras-Go ´mez A, Sa ´nchez-Miro ´ n A, Garcı ´a-Camacho F et al (2014) Protein production using the baculovirus-insect cell
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(1):1–18.
https://doi.org/10.1002/btpr.
1842
63. Maranga L, Cruz PE, Aunins JG et al (2002)
Production of core and virus-like particles
with baculovirus infected insect cells. In:
Schu ¨gerl K, Aunins JG (eds) Tools and
applications of biochemical engineering science, vol 74. Springer, Berlin, pp 183–206
64. Pijlman GP, van den Born E, Martens DE et al
(2001) Autographa californica baculoviruses
with large genomic deletions are rapidly generated in infected insect cells. Virology 283
(1):132–138.
https://doi.org/10.1006/
viro.2001.0854
65. Aucoin MG, Mena JA, Kamen AA (2010)
Bioprocessing of baculovirus vectors: a review.
Curr Gene Ther 10(3):174–186
66. Klo ¨ppinger M, Fertig G, Fraune E et al
(1990) Multistage production of Autographa
californica nuclear polyhedrosis virus in insect
cell cultures. Cytotechnology 4(3):271–278.
https://doi.org/10.1007/bf00563787
67. Zwart MP, Erro E, van Oers MM et al (2008)
Low multiplicity of infection in vivo results in
purifying selection against baculovirus deletion
mutants.
J
Gen
Virol
89
(Pt 5):1220–1224. https://doi.org/10.
1099/vir.0.83645-0
68. Wickham TJ, Davis T, Granados RR et al
(1991) Baculovirus defective interfering particles are responsible for variations in recombinant protein production as a function of
multiplicity of infection. Biotechnol Lett 13
(7):483–488.
https://doi.org/10.1007/
BF01049204
69. Kwang TW, Zeng X, Wang S (2016)
Manufacturing of AcMNPV baculovirus vectors to enable gene therapy trials. Mol Ther
Methods Clin Dev 3:15050. https://doi.
org/10.1038/mtm.2015.50
70. Wolff MW, Reichl U (2011) Downstream
processing of cell culture-derived virus particles. Expert Rev Vaccines 10(10):1451–1475.
https://doi.org/10.1586/erv.11.111
71. Vicente T, Peixoto C, Carrondo MJT et al
(2009) Purification of recombinant baculoviruses for gene therapy using membrane processes. Gene Ther 16(6):766–775. https://
doi.org/10.1038/gt.2009.33
72. Vicente T, Rolda ˜o A, Peixoto C et al (2011)
Large-scale production and purification of
VLP-based vaccines. J Invertebr Pathol 107
(Suppl):S42–S48. https://doi.org/10.1016/
j.jip.2011.05.004
73. Ungerechts G, Bossow S, Leuchs B et al
(2016) Moving oncolytic viruses into the
clinic: clinical-grade production, purification,
and characterization of diverse oncolytic
viruses. Mol Ther Methods Clin Dev
3:16018.
https://doi.org/10.1038/mtm.
2016.18
388
Friederike Eilts et al.
1002/term.2914
55. Yu Y, Liao L, Shao B et al (2017) Knockdown
of microRNA let-7a improves the functionality of bone marrow-derived mesenchymal
stem cells in immunotherapy. Mol Ther 25
(2):480–493.
https://doi.org/10.1016/j.
ymthe.2016.11.015
56. Huang B, Jiang X-C, Zhang T-Y et al (2017)
Peptide modified mesenchymal stem cells as
targeting delivery system transfected with
miR-133b for the treatment of cerebral ischemia. Int J Pharm 531(1):90–100. https://
doi.org/10.1016/j.ijpharm.2017.08.073
57. Balmayor ER, Geiger JP, Koch C et al (2017)
Modified mRNA for BMP-2 in combination
with biomaterials serves as a transcriptactivated matrix for effectively inducing osteogenic pathways in stem cells. Stem Cells Dev
26(1):25–34. https://doi.org/10.1089/scd.
2016.0171
58. Sprick G, Weidner T, Salzig D et al (2017)
Baculovirus-induced recombinant protein
expression in human mesenchymal stromal
stem cells: a promoter study. N Biotechnol
39(Pt B):161–166. https://doi.org/10.
1016/j.nbt.2017.08.006
59. Brooks AR, Harkins RN, Wang P et al (2004)
Transcriptional silencing is associated with
extensive methylation of the CMV promoter
following adenoviral gene delivery to muscle.
J Gene Med 6(4):395–404. https://doi.org/
10.1002/jgm.516
60. Meilinger D, Fellinger K, Bultmann S et al
(2009) Np95 interacts with de novo DNA
methyltransferases, Dnmt3a and Dnmt3b,
and mediates epigenetic silencing of the viral
CMV promoter in embryonic stem cells.
EMBO Rep 10(11):1259–1264. https://
doi.org/10.1038/embor.2009.201
61. Wang J, Zhu L, Chen X et al (2019) Human
bone marrow mesenchymal stem cells functionalized by hybrid baculovirus-adeno-associated
viral
vectors
for
targeting
hypopharyngeal carcinoma. Stem Cells Dev
28(8):543–553. https://doi.org/10.1089/
scd.2018.0252
62. Contreras-Go ´mez A, Sa ´nchez-Miro ´ n A, Garcı ´a-Camacho F et al (2014) Protein production using the baculovirus-insect cell
expression system. Biotechnol Prog 30
(1):1–18.
https://doi.org/10.1002/btpr.
1842
63. Maranga L, Cruz PE, Aunins JG et al (2002)
Production of core and virus-like particles
with baculovirus infected insect cells. In:
Schu ¨gerl K, Aunins JG (eds) Tools and
applications of biochemical engineering science, vol 74. Springer, Berlin, pp 183–206
64. Pijlman GP, van den Born E, Martens DE et al
(2001) Autographa californica baculoviruses
with large genomic deletions are rapidly generated in infected insect cells. Virology 283
(1):132–138.
https://doi.org/10.1006/
viro.2001.0854
65. Aucoin MG, Mena JA, Kamen AA (2010)
Bioprocessing of baculovirus vectors: a review.
Curr Gene Ther 10(3):174–186
66. Klo ¨ppinger M, Fertig G, Fraune E et al
(1990) Multistage production of Autographa
californica nuclear polyhedrosis virus in insect
cell cultures. Cytotechnology 4(3):271–278.
https://doi.org/10.1007/bf00563787
67. Zwart MP, Erro E, van Oers MM et al (2008)
Low multiplicity of infection in vivo results in
purifying selection against baculovirus deletion
mutants.
J
Gen
Virol
89
(Pt 5):1220–1224. https://doi.org/10.
1099/vir.0.83645-0
68. Wickham TJ, Davis T, Granados RR et al
(1991) Baculovirus defective interfering particles are responsible for variations in recombinant protein production as a function of
multiplicity of infection. Biotechnol Lett 13
(7):483–488.
https://doi.org/10.1007/
BF01049204
69. Kwang TW, Zeng X, Wang S (2016)
Manufacturing of AcMNPV baculovirus vectors to enable gene therapy trials. Mol Ther
Methods Clin Dev 3:15050. https://doi.
org/10.1038/mtm.2015.50
70. Wolff MW, Reichl U (2011) Downstream
processing of cell culture-derived virus particles. Expert Rev Vaccines 10(10):1451–1475.
https://doi.org/10.1586/erv.11.111
71. Vicente T, Peixoto C, Carrondo MJT et al
(2009) Purification of recombinant baculoviruses for gene therapy using membrane processes. Gene Ther 16(6):766–775. https://
doi.org/10.1038/gt.2009.33
72. Vicente T, Rolda ˜o A, Peixoto C et al (2011)
Large-scale production and purification of
VLP-based vaccines. J Invertebr Pathol 107
(Suppl):S42–S48. https://doi.org/10.1016/
j.jip.2011.05.004
73. Ungerechts G, Bossow S, Leuchs B et al
(2016) Moving oncolytic viruses into the
clinic: clinical-grade production, purification,
and characterization of diverse oncolytic
viruses. Mol Ther Methods Clin Dev
3:16018.
https://doi.org/10.1038/mtm.
2016.18
388
Friederike Eilts et al.
