The fact that for profit medicine is holding up some of the most advanced medical treatments in history is really disturbing. As a society, there will be a significant benefit, especially once it's cost optimized. But we'll never get there if beancounters hold it up, preferring short term profits above all else. I'd love to know if anyone knows what a solution to this problem might look like.
Even with 100% public healthcare system you have budget constraints. What’s better to provide one treatment for a rare gene decease or cure 10 cancer patients?
I had hemophilia gene therapy. It worked for a period of time but the results were not permanent. The problem with many of the gene therapies is that they do not change the nuclear DNA, they just insert copies of working genes into the cell. If a cell dies, it’s gone. The results aren’t carried through to new cells during division. The other problem is with viral vector based gene therapy is you can’t have it again.…
I am sorry you experience this disease. I have a question: You said " they do not change the nuclear DNA, they just insert copies of working genes into the cell ... The results aren’t carried through to new cells during division. " Isn't this a bit contradictory? I mean, if they insert copies of working genes into the cell, it is in nuclear DNA, so when the cells divide, the daughter cells carry the new gene? I can i…
AAV-based vectors are specifically non-integrating. Wild-type AAVs can integrate, but in the absence of rep protein they will instead persist in the cell nucleus in the form of episomal concatemers - long, circular DNA structures containing multiple copies of the virus DNA. These will not replicate when a cell proliferates - they will instead dilute with each division. This makes them desirable for treating diseases affecting post-mitotic tissue like muscle, less so for, say, bone marrow. Unless transient expression (but not as transient as with NLPs) is what you want.
I am sorry you experience this disease. I have a question: You said " they do not change the nuclear DNA, they just insert copies of working genes into the cell ... The results aren’t carried through to new cells during division. " Isn't this a bit contradictory? I mean, if they insert copies of working genes into the cell, it is in nuclear DNA, so when the cells divide, the daughter cells carry the new gene? I can i…
The working genes they insert are just into the cell envelope itself, not into the cell nucleus. There are actually a lot of DNA that is free floating around in the cell, and are used during protein synthesis, called episome or non-integrated DNA. This is distinct from the DNA inside the nucleus, which gets copied from generation to generation. There are techniques that work on modifying nuclear DNA but from my under…
I am sorry you experience this disease. I have a question: You said " they do not change the nuclear DNA, they just insert copies of working genes into the cell ... The results aren’t carried through to new cells during division. " Isn't this a bit contradictory? I mean, if they insert copies of working genes into the cell, it is in nuclear DNA, so when the cells divide, the daughter cells carry the new gene? I can i…
AAV-based vectors are specifically non-integrating. Wild-type AAVs can integrate, but in the absence of rep protein they will instead persist in the cell nucleus in the form of episomal concatemers - long, circular DNA structures containing multiple copies of the virus DNA. These will not replicate when a cell proliferates - they will instead dilute with each division. This makes them desirable for treating diseases…
Thanks, I thought AAV-based vectors were integrating. Then it's not surprising that some clinical trials using AAV vectors were unsuccessful while the pre-clinical studies were successful, it's looks more a way of cheating than a creating an effective new therapy.