What delivery vector are you planning to use to get the Draco inside every potentially infected cell?
Have you heard of Oisin Biotechnologies and their “fusogenix” lipid nanoparticles?
The original DRACO research used three different transduction tags (also known as Cellular Penetrating Peptides), and found them to be effective at reaching every infected cell. We are planning to use that proven approach, at least at first.
However, in the long term, alternative delivery mechanisms are an area we would very much like to explore. Fusogenix is an interesting one, and there are a few others on our radar, as well.
What's the molecular weight of the VTose system? What is the largest molecular weight that can be encapsulated into a protein transduction tag? Immune reaction is a major side effect of the injected PTTs.
One of the current challenges of injectable PDs is their immune response, rendering them less effective or even causing the production of toxic inhibitory antibodies (immunoglobulin E (IgE)), resulting in anaphylaxis or death. Such inhibitory antibodies form in ~25–30% of patients with severe hemophilia A and in ~5% of severe hemophilia B patients.
Inhibitors seriously complicate clotting factor replacement therapy and thus increase morbidity and mortality of the disease.
https://www.cell.com/molecular-therapy-family/molecular-therapy/fulltext/S1525-0016(16)33585-7
I'm not sure if this would be a problem with the oral form as well.
The molecular weight of VTose is roughly 35 kDa. One of the earliest papers about transduction tags showed effectiveness with a protein with a MW of 120 kDa:
Transport of even larger proteins is undoubtedly possible.
That's encouraging. A low inflammatory diet will minimize immune cytokine damage. Make GcMAF a recommended contraindication as it increases antibody production. If VTose works you shouldn't need it. ME patient antibody production is suppressed anyway by the viral nagalase so it may not end up being a problem.
I caught this story on Oramed which delivers proteins to treat diabetes which are encapsulated and then have increased absorption in the small intesting. Perhaps it might be applicable for VTose.