Hypothesis II: f508d heterozygotes will benefit as much, if not more, from 809/770 Combo
Hypothesis II: f508d Heterzygotes will see as much, if not more success, from 809/770 Combo:
Reasoning: 1. My initial thought for this hypothesis was that with heterzygotes, the non-f508d mutation will likely have more folding, sequencing, or trafficking potential than f508d, and thus will benefit more from 770 alone. I still think this. 2. But recent trolling discovered this additional theory–transcomplementation: In short, there are “many laboratory studies demonstrating that when two different CFTR mutant proteins are co-expressed, mutant CFTR proteins move to the cell surface that would not traffic when expressed alone because of transcomplementation between the mutant proteins.” Full explanation available here: http://luckycfmom.blogspot.com/2012/03/calling-all-heterozygotes.html
I am learning a lot from your hypotheses. Transcomplementation is a reasonable theory. It sounds as if it is related to what molecular geneticist call [rescue] of a defect in a gene by a different defect in the other location. I'll think about what you are saying over the weekend.
Looking forward to your insights. Also, it is possible that with homozygotes that "rescue" occurs or transcomplementation with the remaining mutant protein? In other words, with homozygotes, the 809 and/or 770 fix part of the defect, but not all, and that alters the universe of mutants and their various relationship so the body then readjusts and those new mutants/fixed mutants react with each other differently so have better improvement than what the drugs cause? Wonder if that explains the unexpected stellar results. . . . I also think part of it is explained by the fact that you have proteins on two allelles fixed and not merely the one 551f allelle.