Aside re: compatibility at germ line: not a concern. At least, not a fertility concern. Chromosomal abnormalities are bad because of gene dosage: too many or too few *important* genes due to too many/too few chromosomes. If you had a million copies of a large chromosome that encoded nothing important, the worst you'd suffer would be phosphate deficiency (because of all that wasted DNA).
So a plasmid encoding a "plugin" wouldn't stop you breeding with others lacking the plasmid, but it's an open question as to how inheritance would work: probably depends on the plasmid's segregation system and how it behaves during meiosis.
One area where compatibility *would* be an issue is two people with different 'plugins' on the same plasmid backbone. Interference would cause plasmid loss of one or the other eventually, but how soon after fertilisation? My guess is somewhere in blastocyst stage, with plasmid assortment being effectively random if the systems are identical (copy number, stability etc), so the baby would be chimeric for both traits.
Early enough, and you'd get organ-level chimerism. So your kidneys are green fluorescent, your skin red. Late enough and it'd be intra-organ tissue-level or cell-lineage level. Total chimerism.
Because you're dealing with a random system, likely you'd get a spectrum of chimerism: some completely homogenous organs, some totally blended organs.
What effect this would have depends on the chimeric genes. For curing cystic fibrosis you only need to "cure" a critical percentage of cells to clear the lungs of excess ions, but for something like a myopathy or motor neuron disease you probably need to cure as many as possible: every lost cell is permanent damage.
Speculation is fun!
For my PhD I've been designing plasmids which replicate like a chromosome and can be maintained extrachromosomally (even replicated and delivered to the daughter cells upon proliferation) in the human cell. This completely avoids any integration issues, but it has only been tested in cell cultures.
That sounds awesome. Just make sure the artificial chromosomes won't get into germ cells, else the enhanced human isn't compatible to "old" / "original" humans anymore and interbreed won't be possible I assume.
Of course this method does not allow replacing genes, only adding new ones, but still has a lot of potential IMO.
RNA silencing? Then you can knock out the gene. And add the same gene with another codon usage / or another gene from yeast with the same function.As to AAV itself, yes; you'd expect that a cell pre-infected with an AAV
at its target locus would be immune to re-"infection" with the same
locus-targeting AAV.
But as it is not really seqence dependend, there may be a chance it integrates close to the iother integrated virus DNA?
In case it were sequence specific you could include the targeted sequence in the virus, so it integrates a new integration site :D
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Sent from my Android device with K-9 Mail. Please excuse my brevity.
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