METHODS OF ENHANCING AND EXPEDITING EXPRESSION OF ANTIBODIES

    公开(公告)号:US20240271127A1

    公开(公告)日:2024-08-15

    申请号:US17784796

    申请日:2020-12-15

    摘要: This application describes cells, systems, and molecular engineering methods using CRISPR/Cas complexes for targeted activation of endogenous master transcriptional regulatory elements (MTRE) such as PRDM1, XBP1 and IRF4, to generate high productivity antibody production in production cell lines such as CHO and NSO cells. These incorporate the inclusion of the Cas accessory proteins, design of multiple guide RNAs (gRNA), and unique multiplexing of these components using, e.g., lentiviral transfection to induce increased transcription and translation of antibody genes under the control of the MTRE. The methods result in synergies increasing monoclonal antibody production by these modified cell lines. While a significant increase in productivity is demonstrated by this method of activation, further increase in productivity can be accomplished by genetic transfer of additional copies of MTREs.