Wild question about in situ gene modification

Would it ever be possible to modify the genome in all of a person’s living cells (or just living stem cells or whatever it takes)? If you could, what would happen to that person? Suppose you were able to inject nanobots into someone with Down’s syndrome to tear out or deactivate all those extra #21 chromosomes. Would the effects of Down’s syndrome start to disappear in that person (or has the damage been done, so to speak)? What about other effects, like the gene(s) that controls for eye color?

I expect this is impossible or shows my woeful ignorance of the mechanism of gene expression, but that’s what this site is for.

Thanks,
Rob

It depends on what the gene is for and how and when it’s expressed. But I doubt there are very many genes for which you could produce a superficially-apparent change. Once the brain has grown in a particular way, for instance, it’s not going to re-grow in some different way.

unless you do the modification at a very young stage (aka single cell) the damage in most cases will be permanent. There are a few conditions where the changes might be helpful at any stage, such as inherited clotting factor disorders where all you have to do is convince some cells to start making the necessary clotting factor and all is good.

Somatic gene transfer–that is, the transfer of a new genome or nucleotide sequence into a differentiated cell–is certainly possible and is the basis for post-germline gene therapy. This is often done in the case of cells that are responsible for the production of certain hormones or enzymes to correct a defect that prevents correct production or regulation. Replacing the genome in all cells is well beyond any current technology, nor will it correct post-development conditions such as Down’s Syndrome, which cause gross physical and cognitive abnormalities in the subject that cannot be reversed without reinstating the development process, which would likely result in further abnormal and unregulated development. However, not all genetic material is nuclear; there is also cytoplasmic DNA in organelles within the cell, most notably in mitochondria which serves to regulate energy storage and availability, and is thought to be the cause of many developmental and chronic syndromes. Fixing these issues might not be a matter of replacing the existing defective genome but rather just supplementing it with organelles that function correctly, and this may be feasible.

Eye color is largely governed by melanin production in the iris pigmentation epithelium, and I suspect a gene therapy could be developed to alter that production rate, just as it could be to increase or reduce melanin production in skin (to a certain degree). In fact, it is not unusual for people to experience changes in eye color due to various environmental factors and stressors including pregnancy and use of certain pharmaceuticals. It won’t change someone of sub-Saharan African descent to look like a Swede, but it could make their skin lighter and hair grow somewhat straighter. But the finely specified manipulation of phenotypical expression is well beyond current capabilities in genomics and developmental biology; ordering children built to spec a la Gattaca is still well in the future, although developments in the progress of molecular biology continue to defy projections in how radically fast they advance.

Stranger