Genome-editing techniques to increase the therapeutic efficacy of monoclonal antibodies

The review presents a general description of therapeutic monoclonal antibodies, cell lines used to obtain them, characterizes the reasons for the immunogenicity of recombinant antibodies, and approaches used to eliminate the side effects of therapeutic monoclonal antibodies. The focus is on resolving the immunogenicity problems of fully human therapeutic monoclonal antibodies. The most attention are concentrated on the data of antibody-producing cell genomic editing to increase the yield of the product, the stability of expression of the recombinant protein and reduce its immunogenicity. Modern methods of site-directed modification (zinc finger method, TALEN and CRISPR/CAS9) for editing the genome of the CHO cell line are analyzed. The strategies of genomic editing choice carrying out taking into account the advances of omix technologies are discussed. Approaches to increase the life span of producer cells are considered, including an increase in the expression of anti-apoptotic signals and the deletion of proapoptotic genes, an increase in the duration of the cell cycle of cells in the G0/G1 phase. The approaches used to regulate the posttranslational modification of monoclonal antibodies are considered. Significant part of the review are devoted to the discussion of the spesificity and differences of glycosylation, galactosylation and sialization of monoclonal antibodies in different expression systems and the associated different degree of immunogenicity of monoclonal antibodies. The main approaches to the regulation of the synthesis of monoclonal antibodies at the stage of translation using non-coding RNA are considered.