>Then why doesn’t the phrasing say, “without any risk of incorporation”? “Without any requirement of incorporation” sounds like they are stopping short of asserting that there is no incorporation.<
Because it is theoretically possible for the plasmid to incorporate into the genome. Circular plasmids (as i believe this one most likely is) do not incorporate well at all. When linearized, such plasmids are more likely to incorporate.
They say "without requirement" simply because there is no integration requirement for the plasmid to start vegf production. On the other hand, it is very, very difficult for them to determine if there has been incorporation, so in the absence of data, they can't say that there is no incorporation. So you're left with writing something that is technically correct, but not overly informative.
As for how devastating the impact... well, a biowatch said, the majority of the genome has vast spaces full of nothing (at least that's what we think). So if it incorporates in these areas, then the effect should be nil. If it incorporated into an essential gene, that cardiomyocyte would likely turn nonfunctional. Won't help their attempt at demonstrating efficacy, but it won't kill anybody either.
The bigger problem in this approach is that the VEGF has to bind to its receptors on the cell surface. So the VEGF produced inside the cell with this approach has to properly cycle to the exterior of the cell, and then find its receptor. I think this raises the bar a bit on trying to demonstrate efficacy.
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