aslan2772, thanks for the reply....
You said,
<<<<<For the sake of argument, if GTCB wanted to produce exclusively antithrombin alpha, all they would have to do is make a point mutation, converting serine 137 to a threonine, creating a NXT consensus sequence. This would most likely work just fine.
<<<<<<<
I think you've presented a fairly reasonable hypothesis for testing. I guess my point still is, that , it's not that easy.
1. The proteins were tested in insect cells, it's most likely that secretory pathways between goat and insect are quite divergent. Just because one achieves more efficient glycosylation in one organism doesnt mean its going to translate to another.
2. Your mutation has now altered the natural primary sequence of the protein. I know its just one carbon, but Ive seen a valine to an alanine substitution alter protein activity 10-fold. You have to make sure activity of variant doesnt take too big of a hit.
3. Any time you mutate a protein away from its natural sequence, you raise the stakes in the immunogenicity game, (although it's not a factor here, because this an acute indication)
4. You're also assuming that residue is not patented by the original discoverers.
5. The point you raised about the goat expression timelines is EXCELLENT. Because of the work/time involved to set up a transgenic goat, you don't want to use a goat to start screening variants.
Thanks so much for the thoughtful reply. It's FAR more stimulating conversation than, "GTC scientists are smart, they'll figure it out".
Take Care, PC
AI
