How would you effect bulk DNA gene therapy for a human?
Let's imagine that we understood DNA programming and our genome very well and >realized that there were some significant flaws (we die, we need sleep, etc.) And >let's imagine that we understand how to make our genome do what we want, but it's a >major refactor. We're going to have adjust 10-15% of our DNA.


I think we both recognise that this is a very naive view of biology and the nature of how organismal properties emerge (through multiple levels of systems) ultimately from the genetic code, the information in the genome, and the developmental process.

It is more pertinent and promising to think about treating genetic diseases.

Some genetic diseases are caused by mutations to single basepairs (e.g. the HgbS variant of the haemoglobin beta chain, which causes sickle-cell anaemia).
Other genetic diseases are caused by rearrangements of large segments of chromosomes, and the gene dosage imbalances that arise from this (e.g. Charcot-Marie-Tooth syndrome 1A). Finally, some genetic diseases are caused by a major gene-dosage imbalance caused by having an unusual set of chromosomes, "aneuploidy" (e.g. down syndrome, where chromosome 21 is present in 3 copies).

'Large-scale' gene therapy could be something useful for aneuploidy. Recently, the mechanism for inactivating one X-chromosome in female somatic cells has been applied to silencing the surplus chromosome 21 of Down Syndrome.

In yeast, a 'designer chromosome' has been chemically synthesised, and has been used to replace the corresponding native chromosome in yeast cells.

So although I think the premise of your question is basically science-fiction and naive, it is becoming possible to silence or replace whole chromosomes. More realistically than making our species immortal and ever-awake, this technology could possibly translate to therapies for some genetic diseases. But of course, the problem of retrospectively getting your therapy in to many somatic cells is still there. Engineering zygotes is feasible but has ethical problems - also, where pre-implantation screening is permitted, IVF can simply include genetic selection rather than genetic engineering!