Predicting genetically stable recombinant protein production in early cell line development

Method for selecting a suitable candidate cell clone for recombinant protein expression, the method comprising the steps of:

• a) determining for at least two cell clones the RNA expression level of a marker gene selected from the group consisting of:
• histone cluster 1, H2bc Gene (Hist1h2bc), early growth response 1 gene (Egr1), Mouse DNA sequence from clone RP23-293P3 on chromosome 2/histone cluster 1, H3c (BX842664.2/Hist1h3c), dihydrofolate reductase (Dhfr), fibroblast growth factor receptor 2 (Fgfr2), AC115880.11, matrix metallopeptidase 10 (Mmp10), CU459186.17, E130203B14Rik, chondroitin sulfate proteoglycan 4 gene (Cspg4), C1q and tumor necrosis factor related protein 1 (C1qtnf1), forkhead box P2 gene (Foxp2), visinin-like 1 (Vsnl1), and protein tyrosine phosphatase, receptor type E (Ptpre), and
• b) selecting out of said at least two cell clones a cell clone for further expansion, whose RNA expression level of said gene is with respect to the expression level of said same gene in at least one other clone tested in step a):
• i) upregulated, if the gene is a gene selected from the group of genes consisting of:
• Hist1h2bc, BX842664.2/Hist1h3c, Dhfr, AC115880.11, Fgfr2, Mmp10, Vsnl1 and CU459186.17, or
• ii) downregulated, if the gene is a gene selected from the group of genes consisting of:
• Egr1, E130203B14Rik, Cspg4, C1qtnf1, Foxp2, and Ptpre.