The Coming Age of Insect Cells for Manufacturing and Development of Protein Therapeutics

Abstract

Protein therapeutics is a rapidly growing segment of the pharmaceutical market. Currently, the majority of protein therapeutics are manufactured in mammalian cells for their ability to generate safe and efficacious human-like glycoproteins. The high cost of using mammalian cells for manufacturing has motivated a constant search for alternative host platforms. Insect cells have begun to emerge as a promising candidate, largely due to the development of the baculovirus expression vector system. While there are continuing efforts to improve insect-baculovirus expression for producing protein therapeutics, key limitations including cell lysis and the lack of homogeneous humanized glycosylation still remain. The field has started to see a movement toward virus-less gene expression approaches, notably the use of clustered regularly interspaced short palindromic repeats to address these shortcomings. This review highlights recent technological advances that are realizing the transformative potential of insect cells for the manufacturing and development of protein therapeutics.

Rapid microsphere‐assisted peptide screening (MAPS) of promiscuous MHCII‐binding peptides in Zika virus envelope protein

“…The MAPS strategy introduced here addresses such a need by providing a simple method for identifying immunologically relevant, promiscuous MHCII‐binding peptides. Incorporation of the MAPS strategy into the vaccine development process could accelerate T cell epitope identification and expedite the development and manufacturing of novel vaccines . Beyond vaccine development, our observations indicate that MAPS and similar screening strategies should provide valuable insights relevant to broadly applicable peptide‐based therapies, vaccines, and diagnostic tools necessary to protect ethnically diverse populations.…”

Recent Developments in Bioprocessing of Recombinant Proteins: Expression Hosts and Process Development

“…Insect cells are not able to carry out Nglycosylation, but this issue can be solved by introducing mammalian glycosyltransferases into insect cells or by the coexpression of these enzymes together with the gene of interest in baculoviruses (Le et al, 2018). The most common cell line used for the baculovirus expression system is Sf9 (Van Oers et al, 2018;Yee et al, 2018;Ghasemi et al, 2019). In addition to Sf9 cells, S2, Sf21, Tn-368, and High-Five TM cells are also used for the expression of recombinant proteins (Contreras-Gómez et al, 2014;Felberbaum, 2015).…”

“…CRISPR is expected to instigate a rapid expansion of engineering approaches to achieve enhanced expression of multiple genes in insect cells. These current and expected future developments in engineering insect cells for enhanced expression of humanized proteins are dissolving perceived disadvantages to bring about the upcoming age of the use of insect cells for the development and manufacturing of therapeutic proteins (Yee et al, 2018). Pazmiño-Ibarra et al (2019) reported the use of a CRISPR/Cas9 system for the engineering of baculovirus to improve its performance as a protein expression vector.…”

Synthetic Glycobiology: Parts, Systems, and Applications

“… 138 , 193 (b) Insect cell and insect cell-based baculovirus glycosylation systems have been remodeled to obtain full-length bianntenary N-linked glycans without α1,3 fucose residues. 194 (c) Remodeled plant glycosylation systems have reduced arabinosylation of prolines and produced human O -GalNAc glycans and full-length bianntenary N -linked glycans. 195 (d) Extensive remodeling of yeast glycosylation pathways have worked to eliminate oligo-mannose structures from N - and O -linked glycans and introduce human terminally sialylated, full-length human O -linked and N -linked glycans.…”