Transposon vector-mediated stable gene transfer for the accelerated establishment of recombinant mammalian cell pools allowing for high-yield production of biologics

Biotechnol Lett. 2020 Jul;42(7):1103-1112. doi: 10.1007/s10529-020-02889-y. Epub 2020 Apr 22.

Abstract

Stable recombinant mammalian cells are of growing importance in pharmaceutical biotechnology production scenarios for biologics such as monoclonal antibodies, growth and blood factors, cytokines and subunit vaccines. However, the establishment of recombinant producer cells using classical stable transfection of plasmid DNA is hampered by low stable gene transfer efficiencies. Consequently, subsequent selection of transgenic cells and the screening of clonal cell populations are time- and thus cost-intensive. To overcome these limitations, expression cassettes were embedded into transposon-derived donor vectors. Upon the co-transfection with transposase-encoding constructs, elevated vector copy numbers stably integrated into the genomes of the host cells are readily achieved facilitating under stringent selection pressure the establishment of cell pools characterized by sustained and high-yield recombinant protein production. Here, we discuss some aspects of transposon vector technologies, which render these vectors promising candidates for their further utilization in the production of biologics.

Keywords: Mammalian cells; Protein production; Sleeping Beauty; Transposon vector; piggyBac.

Publication types

  • Review

MeSH terms

  • Animals
  • Biological Products* / analysis
  • Biological Products* / metabolism
  • Cell Line
  • DNA Transposable Elements / genetics*
  • Genetic Vectors / genetics*
  • Humans
  • Mammals
  • Recombinant Proteins* / analysis
  • Recombinant Proteins* / genetics
  • Recombinant Proteins* / metabolism
  • Transfection / methods*

Substances

  • Biological Products
  • DNA Transposable Elements
  • Recombinant Proteins