mn dit stuk,
We have developed the CAP-Go protein expression platform, an expression system based on human cells,
to confer optimal glycosylation to complex glycoproteins such as C1-Inh. The CAP-Go.1 cell line has been
modified to facilitate expression of proteins with fully sialylated N-glycans. Recombinant proteins like human
alpha-antitrypsin or human placental alkaline phosphatase produced with CAP-Go.1 show a significantly
prolonged serum half-life in rats. However, expression of rhC1-Inh in CAP-Go.1 cells had no positive impact
on the pharmacokinetic profile.
Expression of rhC1-Inh in CAP-Go.2 cells, which in addition addresses the O-linked glycosylation patterns,
results in a significantly increased serum half-life which is actually indistinguishable from the plasma-purified
protein. O-glycan analysis shows that rhC1-Inh expressed by CAP-Go.2 cells contains only highly sialylated
core1 O-glycan structures, highly comparable to plasma-derived Berinert. Our results demonstrate that in addition
to N-glycosylation, the structure of O-linked glycans plays a crucial role in bioavailability and pharmacokinetic
properties of glycoproteins.
In conclusion, rhC1-Inh expressed from CAP-Go.2 cells, matches serum-derived C1-Inh in all analyzed aspects
- specific activity, serum half-life, and glycosylation pattern - and offers the advantage of being producible at
large scale on a safe platform