| Id |
Subject |
Object |
Predicate |
Lexical cue |
| T1 |
0-120 |
Sentence |
denotes |
Enhancing the sialylation of recombinant EPO produced in CHO cells via the inhibition of glycosphingolipid biosynthesis. |
| T2 |
121-244 |
Sentence |
denotes |
Sialylation regulates the in vivo half-life of recombinant therapeutic glycoproteins, affecting their therapeutic efficacy. |
| T3 |
245-405 |
Sentence |
denotes |
Levels of the precursor molecule cytidine monophospho-N-acetylneuraminic acid (CMP-Neu5Ac) are considered a limiting factor in the sialylation of glycoproteins. |
| T4 |
406-625 |
Sentence |
denotes |
Here, we show that by reducing the amount of intracellular CMP-Neu5Ac consumed for glycosphingolipid (GSL) biosynthesis, we can increase the sialylation of recombinant human erythropoietin (rhEPO) produced in CHO cells. |
| T5 |
626-766 |
Sentence |
denotes |
Initially, we found that treating CHO cells with a potent inhibitor of GSL biosynthesis increases the sialylation of the rhEPO they produce. |
| T6 |
767-943 |
Sentence |
denotes |
Then, we established a stable CHO cell line that produces rhEPO in the context of repression of the key GSL biosynthetic enzyme UDP-glucose ceramide glucosyltransferase (UGCG). |
| T7 |
944-1061 |
Sentence |
denotes |
These UGCG-depleted cells show reduced levels of gangliosides and significantly elevated levels of rhEPO sialylation. |
| T8 |
1062-1294 |
Sentence |
denotes |
Upon further analysis of the resulting N-glycosylation pattern, we discovered that the enhanced rhEPO sialylation could be attributed to a decrease in neutral and mono-sialylated N-glycans and an increase in di-sialylated N-glycans. |
| T9 |
1295-1492 |
Sentence |
denotes |
Our results suggest that the therapeutic efficacy of rhEPO produced in CHO cells can be improved by shunting intracellular CMP-Neu5Ac away from GSL biosynthesis and toward glycoprotein sialylation. |
