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I don't get this gene treatment at all. We are told: > The gene therapy consists of a harmless virus carrying new otoferlin genes in two drops of liquid that

I don't get this gene treatment at all. We are told: > The gene therapy consists of a harmless virus carrying new otoferlin genes in two drops of liquid that are delicately injected down the length of the cochlea, delivering the genes to each hair cell. You just squirt some medicine near the cells, and then the cells are sorted? This is no explanation at all. You could say, 'the cells absorb the protein and as the completes the bio-circuit, it is now activated correctly and the patient can hear'. Obviously I just made that up! But how does the thing work? Eg, if this was cancer and you operated to take the cancer out, fine - I get the principle. It if it's chemo, you insert some chemicals typically and it kills the cancerous growth, I get that too. But what is the gene therapy doing, at an engineering level? It's a mystery to me. Frankly, while I can understand a gene therapy working when treating a fetus, I don't get how it can work once the cells are developed and in place. I'm sure I'm dumb, but there it is. The whole article reads like a gene therapy promo, with no details that help understanding what the treatment is. You might as well say 'magic'.

immersible 3y ago
It is funny that this supposed hereditary deafness is caused by what they call a "nonsense mutation". "Yasunaga S. et al. (1999) showed that the affected individuals in this family were homozygous for a nonsense mutation in the OTOF gene. " (retrieved in 2024/jan/24 from https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/otof https://www.sciencedirect.com/topics/biochemistry-genetics-a...)
tsol 3y ago
It's kind of amazing. The issue is that the cells have a dysfunctional copy of the OTOH gene, which leads to production of a dysfunctional otoferlin protein that does not work. There are virii that inject their DNA into cells. They modify one of these to make them inject a working copy of the OTOH gene into the cell. Cells have a mechanism where if there is a gene floating around nearby it will sometimes pick it up and integrate it. This is the process that is exploited in gene therapy to change individual cells to produce the correct protein. If enough cells produce the correct protein, there will be enough to have the desired effects. It's really unbelievably cool. I wish there were more appreciation for how these things work.
- verisimi 3y ago
  Thanks for the explanation. That is amazing. What happens to the dysfunctional copy of the gene, I wonder? And what happens when the cell dies?

immersible 3y ago

It is funny that this supposed hereditary deafness is caused by what they call a "nonsense mutation". "Yasunaga S. et al. (1999) showed that the affected individuals in this family were homozygous for a nonsense mutation in the OTOF gene. " (retrieved in 2024/jan/24 from https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/otof https://www.sciencedirect.com/topics/biochemistry-genetics-a...)

tsol 3y ago

It's kind of amazing. The issue is that the cells have a dysfunctional copy of the OTOH gene, which leads to production of a dysfunctional otoferlin protein that does not work. There are virii that inject their DNA into cells. They modify one of these to make them inject a working copy of the OTOH gene into the cell. Cells have a mechanism where if there is a gene floating around nearby it will sometimes pick it up and integrate it. This is the process that is exploited in gene therapy to change individual cells to produce the correct protein. If enough cells produce the correct protein, there will be enough to have the desired effects. It's really unbelievably cool. I wish there were more appreciation for how these things work.

verisimi 3y ago
Thanks for the explanation. That is amazing. What happens to the dysfunctional copy of the gene, I wonder? And what happens when the cell dies?