Optimization of monoclonal antibody expression in CHOcells by employing epigenetic gene regulation tools

摘要: Monoclonal antibodies (mAbs) are crucial in pharmaceutical biotechnology. Mammalian cell lines the most preferred for their production. One of significant challenging issues mammalian expression systems is epigenetic gene silencing. Employing regulation tools can increase productivity lines. Sodium butyrate (NaBut) and valproic acid (VPA) regulate by inhibiting histone deacetylase. A ubiquitous chromatin-opening element (UCOE) improve reducing DNA methylation. Here, separate combined effects NaBut VPA deacetylase inhibitors (iHDACs) UCOE on mAb synthesis were studied. Stable generated non-UCOE (CHO-HL) UCOE-containing vectors (CHO-UHUL) cultured presence absence or VPA. Expression analysis showed that CHO-UHUL gave a 4-fold greater yield than CHO-HL. Antibody production levels CHO-HL cells increased 2-fold 2.5-fold after treatment, respectively. These results indicate has more impact antibody iHDACs. iHDAC treatment exhibited at least 0.5-fold higher containing cells. Thus utilization resulted improvement, use them had synergistic effect synthesis. Keywords: antibodies, Chinese hamster ovary, silencing, element, sodium butyrate,