Date: 2022-03-28 17:00 ~ 19:00
Speaker: Sunghwa Choe (SNU School of Biological Sciences)
Professor: 생명과학부
Location: 26동 B102호
Glycans that are post-translationally attached to therapeutic proteins play crucial role in distribution,
pharmacokinetics, and efficacy of the proteins in human body. However, systemic approach to screen for the
desirable relationship between glycosylation pattern and efficacy of the proteins has awaited to be available.
Here, we created seven host plants of Nicotiana benthamiana which are different in generating protein glycan
patterns by using CRISPR-Cas9 genome editing technology. The so-called ‘Glyco-scan system’ consists in the
seven genome-edited plants being knocked out of a single glycosyltransferase function like Fucose, Xylose, or
Galactose transferase, respectively, and combination of the two, and all the three functions at the same time.
These plants exhibited visibly non-distinguishable phenotypes, but the protein glycosylation pattern was
different as designed relative to wild-type plants. Using a viral expression vector system and vacuum infiltration
of the vector-harboring Agrobacterium, the Trastuzumab monoclonal antibodies were expressed in the the whole process of the protein production took approximately six weeks from the gene cloning step to obtaining the purified proteins at hands. In terms
of the therapeutic activity, less than half the amount of the original Trastuzumab was required to have an equal
level of activity in antibody-dependent cellular cytotoxicity (ADCC) study. In a mouse breast cancer xenograft
model, the final size of the tumors was approximately 30% smaller than those treated with the original
Trastuzumab antibody. Our Glyco-scan system provides a quick and efficient methods of testing different
glycosylation patterns in therapeutic proteins such as monoclonal antibodies, cytokines, enzymes, and
antigens. When integrated into biologics-development programs, the Glyco-scan system could help identify the
better glycan forms of the concerned proteins in a previously unexplorable way.