Selection, Gene amplification and cell line screening


•   Selection of transfected cells in presence of antibiotics such as neomycin, hygromycin and puromycin.

        DHFR expression systems:
   –    Expression of r-proteins can increase by exposing cells to methotrexate (MTX)
       MTX can block the activity of DHFR
   –    After 2-3 weeks of the MTX exposure only cells which overproduce DHFR can survive

Glutamine Synthetase (GS) gene expression system
  -    Expression vector encoading product gene plus GS gene, allowing glutamine synthesis
  -    GS is inhibited by methionine sulphoximine (MSX)
  -    Selection in the glutamine free medium for GS minus cell types(e.g.NSO)
  -    Selection in the presence of MSX for GS positive cell types (e.g. CHO)
  -    Only cells with GS gene - selects for rare integration into transcriptionally efficient cites in genome
  -    Expression of linked product gene, driven by strong promotor, enhanced by favourable integration sites.

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