Development of Magoh protein‐overexpressing HEK cells for optimized therapeutic protein production

PRIETO, CLAUDIO C.; ETCHEVERRIGARAY, MARINA; BENIZIO, EVANGELINA L.; RODRIGUEZ, MARÍA CELESTE; MUFARREGE, EDUARDO F.; CHIAPPINI, FABRICIO; KRATJE, RICARDO B.

BIOTECHNOLOGY AND APPLIED BIOCHEMISTRY

PORTLAND PRESS LTD

Lugar: Londres; Año: 2020 p. 230 - 238

0885-4513

In the pharmaceutical industry, the need for high levels ofprotein expression in mammalian cells has prompted thesearch for new strategies, including technologies to obtaincells with improved mechanisms that enhance itstranscriptional activity, folding, or protein secretion. ChineseHamster Ovary (CHO) cells are by far the most used host cellfor therapeutic protein expression. However, these cellsproduce specific glycans that are not present in human cellsand therefore potentially immunogenic. As a result, there is anincreased interest in the use of human-derived cells fortherapeutic protein production. For many decades, humanembryonic kidney (HEK) cells were exclusively used forresearch. However, two products for therapeutic indicationwere recently approved in the United States. It was previouslyshown that tethered Magoh, an Exon-junction complex corecomponent, to specific mRNA sequences, have had significantpositive effects on mRNA translational efficiency. In this study,a HEK Magoh-overexpressing cell line and clones, designatedhere as HEK-MAGO, were developed for the first time. Thesecells exhibited improved characteristics in protein expression,reaching ?two- to threefold increases in rhEPO proteinproduction in comparison with the wild-type cells. Moreover,this effect was promoter independent highlighting theC 2020 International Unionversatility of this expression platform. of Biochemistry and Molecular Biology, Inc. Volume 00, Number 0, Pages1?9, 2020