A Review of Alternative Promoters for Optimal Recombinant Protein Expression in Baculovirus-infected Insect Cells

Overview

Journal Protein Expr Purif

Specialty Molecular Biology

Date 2021 Jun 4

PMID 34087362

Citations 11

Authors

Carissa Grose

Zoe Putman

Dominic Esposito

Affiliations

Soon will be listed here.

Abstract

Generating recombinant proteins in insect cells has been made possible via the use of the Baculovirus Expression Vector System (BEVS). Despite the success of many proteins via this platform, some targets remain a challenge due to issues such as cytopathic effects, the unpredictable nature of co-infection and co-expressions, and baculovirus genome instability. Many promoters have been assayed for the purpose of expressing diverse proteins in insect cells, and yet there remains a lack of implementation of those results when reviewing the landscape of commercially available baculovirus vectors. In advancing the platform to produce a greater variety of proteins and complexes, the development of such constructs cannot be avoided. A better understanding of viral gene regulation and promoter options including viral, synthetic, and insect-derived promoters will be beneficial to researchers looking to utilize BEVS by recruiting these intricate mechanisms of gene regulation for heterologous gene expression. Here we summarize some of the developments that could be utilized to improve the expression of recombinant proteins and multi-protein complexes in insect cells.

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References

Vijayachandran L, Thimiri Govinda Raj D, Edelweiss E, Gupta K, Maier J, Gordeliy V . Gene gymnastics: Synthetic biology for baculovirus expression vector system engineering. Bioengineered. 2013; 4(5):279-87. PMC: 3813527. DOI: 10.4161/bioe.22966. View

Palomares L, Mena J, Ramirez O . Simultaneous expression of recombinant proteins in the insect cell-baculovirus system: production of virus-like particles. Methods. 2012; 56(3):389-95. DOI: 10.1016/j.ymeth.2012.01.004. View

Daniels R, Rossano A, Macleod G, Ganetzky B . Expression of multiple transgenes from a single construct using viral 2A peptides in Drosophila. PLoS One. 2014; 9(6):e100637. PMC: 4063965. DOI: 10.1371/journal.pone.0100637. View

Glocker B, Hoopes Jr R, Hodges L, Rohrmann G . In vitro transcription from baculovirus late gene promoters: accurate mRNA initiation by nuclear extracts prepared from infected Spodoptera frugiperda cells. J Virol. 1993; 67(7):3771-6. PMC: 237741. DOI: 10.1128/JVI.67.7.3771-3776.1993. View

Viswanathan P, Venkaiah B, Kumar M, Rasheedi S, Vrati S, Bashyam M . The homologous region sequence (hr1) of Autographa californica multinucleocapsid polyhedrosis virus can enhance transcription from non-baculoviral promoters in mammalian cells. J Biol Chem. 2003; 278(52):52564-71. DOI: 10.1074/jbc.M309351200. View

Fuchs L, Woods M, Weaver R . Viral Transcription During Autographa californica Nuclear Polyhedrosis Virus Infection: a Novel RNA Polymerase Induced in Infected Spodoptera frugiperda Cells. J Virol. 1983; 48(3):641-6. PMC: 255395. DOI: 10.1128/JVI.48.3.641-646.1983. View

Toth A, Kuo C, Khoo K, Jarvis D . A new insect cell glycoengineering approach provides baculovirus-inducible glycogene expression and increases human-type glycosylation efficiency. J Biotechnol. 2014; 182-183:19-29. PMC: 4095979. DOI: 10.1016/j.jbiotec.2014.04.011. View

Chen W, Chang Y, Chen Y, Chen Y, Teng C, Wang C . Development of a prokaryotic-like polycistronic baculovirus expression vector by the linkage of two internal ribosome entry sites. J Virol Methods. 2009; 159(2):152-9. DOI: 10.1016/j.jviromet.2009.03.019. View

Jarvis D, Fleming J, Kovacs G, Summers M, Guarino L . Use of early baculovirus promoters for continuous expression and efficient processing of foreign gene products in stably transformed lepidopteran cells. Biotechnology (N Y). 1990; 8(10):950-5. DOI: 10.1038/nbt1090-950. View

10.

Pijlman G, Roode E, Fan X, Roberts L, Belsham G, Vlak J . Stabilized baculovirus vector expressing a heterologous gene and GP64 from a single bicistronic transcript. J Biotechnol. 2005; 123(1):13-21. DOI: 10.1016/j.jbiotec.2005.10.022. View

11.

Krappa R . Identification of the very early transcribed baculovirus gene PE-38. J Virol. 1991; 65(2):805-12. PMC: 239820. DOI: 10.1128/JVI.65.2.805-812.1991. View

12.

Rankl N, Rice J, Gurganus T, Barbee J, Burns D . The production of an active protein kinase C-delta in insect cells is greatly enhanced by the use of the basic protein promoter. Protein Expr Purif. 1994; 5(4):346-56. DOI: 10.1006/prep.1994.1051. View

13.

Cha H, Dalal N, Pham M, Kramer S, Vakharia V, Bentley W . Monitoring foreign protein expression under baculovirus p10 and polh promoters in insect larvae. Biotechniques. 2002; 32(5):986, 988, 990 passim. DOI: 10.2144/02325bm02. View

14.

George Kamita S, Maeda S, Hammock B . High-frequency homologous recombination between baculoviruses involves DNA replication. J Virol. 2003; 77(24):13053-61. PMC: 296086. DOI: 10.1128/jvi.77.24.13053-13061.2003. View

15.

Berger I, Fitzgerald D, Richmond T . Baculovirus expression system for heterologous multiprotein complexes. Nat Biotechnol. 2004; 22(12):1583-7. DOI: 10.1038/nbt1036. View

16.

Habib S, Pandey S, Chatterji U, Burma S, Ahmad R, Jain A . Bifunctionality of the AcMNPV homologous region sequence (hr1): enhancer and ori functions have different sequence requirements. DNA Cell Biol. 1996; 15(9):737-47. DOI: 10.1089/dna.1996.15.737. View

17.

Theilmann D, Stewart S . Identification and characterization of the IE-1 gene of Orgyia pseudotsugata multicapsid nuclear polyhedrosis virus. Virology. 1991; 180(2):492-508. DOI: 10.1016/0042-6822(91)90063-h. View

18.

Jin J, Dong W, Guarino L . The LEF-4 subunit of baculovirus RNA polymerase has RNA 5'-triphosphatase and ATPase activities. J Virol. 1998; 72(12):10011-9. PMC: 110520. DOI: 10.1128/JVI.72.12.10011-10019.1998. View

19.

Lee D, Chen C, Hsu T, Juang J . A baculovirus superinfection system: efficient vehicle for gene transfer into Drosophila S2 cells. J Virol. 2000; 74(24):11873-80. PMC: 112470. DOI: 10.1128/jvi.74.24.11873-11880.2000. View

20.

Yang S, Miller L . Activation of baculovirus very late promoters by interaction with very late factor 1. J Virol. 1999; 73(4):3404-9. PMC: 104104. DOI: 10.1128/JVI.73.4.3404-3409.1999. View