I actually think we can pretty much eliminate the risk of arbitrarily large side-effects. There are databases of known genetic variants that cause serious illness or death. As long as you can avoid edits to those varaints you should be fine.
Nearly all the variants you would target are present in at least 1% of some reference population, so the maximum “downside” would be the sum of the differences between that reference populations lives and those without the variant for all variants you edit (plus any effects from off-targets).
Off targets ARE a concern, but there are ways to significantly reduce the risk of such edits. For example if you want to change a sequence AAA to AGA, you’re better off using a prime editor to avoid bystander edits that are common among base editors (at least you’re better off if bystander edits are actually a concern)
so the maximum “downside” would be the sum of the differences between that reference populations lives and those without the variant for all variants you edit (plus any effects from off-targets)
I don’t think that’s true? It has to assume the variants don’t interact with each other. Your reference population would only have 0.01% people with (the rarest) 2 variants at once, 0.0001% with 3 variants, and so on.
I actually think we can pretty much eliminate the risk of arbitrarily large side-effects. There are databases of known genetic variants that cause serious illness or death. As long as you can avoid edits to those varaints you should be fine.
Nearly all the variants you would target are present in at least 1% of some reference population, so the maximum “downside” would be the sum of the differences between that reference populations lives and those without the variant for all variants you edit (plus any effects from off-targets).
Off targets ARE a concern, but there are ways to significantly reduce the risk of such edits. For example if you want to change a sequence AAA to AGA, you’re better off using a prime editor to avoid bystander edits that are common among base editors (at least you’re better off if bystander edits are actually a concern)
I don’t think that’s true? It has to assume the variants don’t interact with each other. Your reference population would only have 0.01% people with (the rarest) 2 variants at once, 0.0001% with 3 variants, and so on.