Mammalian cells genetic manipulations for enhanced monoclonal antibody production: from traditional to novel trends, a review

Abstract

Novel therapeutics and monoclonal antibodies (mAbs) specifically, are under massive demands for the treatment of various illnesses. Research in cell engineering has been able to develop mammalian cell lines able to produce higher yields of potent recombinant proteins using different genetic manipulations. However, the public demands for these potent drugs keep increasing and as such, it is needed for the field of biopharmaceuticals to create highly efficient producers to increase volumetric productivity and lower overall costs. Several ways have been investigated up to date, from impacting on cells' natural growth pattern, by apoptosis regulation and cell cycle control, enhancement of its production pathways, by stimulating secretary factors, and production of enzymes to use growth-related metabolites. These approaches, most of the time, involve a considerable amount of resources and time, with an impact mostly on a couple of natural traits of mammalian cells. The ideal scenario is to use other vectors to impact entire pathways and the global cellular functioning to provide better workhorses. Novel approaches, namely micro RNAs (miRNAs), RNA interferences (RNAi) and CRISPR/Cas9, have been used in the last few years and have demonstrated a broader impact on cellular pathways, and also more efficiency in recombinant genes transfection or complete knock-out of specific sequences. In this review, traditional and novel aspects are described, discussed while expressing what approach to be taken next would be of interest, from a productivity standpoint.