I don’t particularly see why the same class of errors in regulatory regions couldn’t cause a protein to stop being expressed entirely or accidentally up/down-regulate expression by quite a lot, having similar side effects. But it’s getting into the practical details of gene editing implementation so no idea.
A bad enough error in a regulatory region could cause a protein to stop being expressed. But the insertion or deletion of a single base pair is not nearly as devastating.
Let me explain by talking through how a promoter works.
Promoters sit upstream of a region of the genome that codes for a protein. They generally serve as a binding site for a very important enzyme called RNA polymerase, whose job it is to transcribe DNA into mRNA, which can then be exported from the nucleus and turned into proteins.
You can delete a letter from a promoter and RNA polymerase will still be able to bind. The “binding affinity” (meaning the strength of the bond) will be affected by this deletion, but except in rare circumstances it will still work.
You can see this reflected in the distribution of insertion and deletions throughout the genome; there’s not that many in coding regions, but there are tons in non-coding regions (on the order of 3-5 million).
Oh, ok, the mechanism is familiar to me and in hindsight this makes sense !
But then, my follow-up would be, if all you are doing is up/down-regulating certain proteins or regions encoding several proteins wouldn’t you be able to more easily either get the proteins or plasmids or RNAviruses expressing the proteins into the brain ? Which would be temporary but could be long lasting (and cheap) and would not pose this risk
I don’t particularly see why the same class of errors in regulatory regions couldn’t cause a protein to stop being expressed entirely or accidentally up/down-regulate expression by quite a lot, having similar side effects. But it’s getting into the practical details of gene editing implementation so no idea.
A bad enough error in a regulatory region could cause a protein to stop being expressed. But the insertion or deletion of a single base pair is not nearly as devastating.
Let me explain by talking through how a promoter works.
Promoters sit upstream of a region of the genome that codes for a protein. They generally serve as a binding site for a very important enzyme called RNA polymerase, whose job it is to transcribe DNA into mRNA, which can then be exported from the nucleus and turned into proteins.
You can delete a letter from a promoter and RNA polymerase will still be able to bind. The “binding affinity” (meaning the strength of the bond) will be affected by this deletion, but except in rare circumstances it will still work.
You can see this reflected in the distribution of insertion and deletions throughout the genome; there’s not that many in coding regions, but there are tons in non-coding regions (on the order of 3-5 million).
Oh, ok, the mechanism is familiar to me and in hindsight this makes sense !
But then, my follow-up would be, if all you are doing is up/down-regulating certain proteins or regions encoding several proteins wouldn’t you be able to more easily either get the proteins or plasmids or RNAviruses expressing the proteins into the brain ? Which would be temporary but could be long lasting (and cheap) and would not pose this risk