If you want to zero out mutational load and create a modal genome, you’re approximately 2 orders of magnitude off in the number of edits you need to do. (The number of evolutionarily-conserved protein-coding regions has little to do with the number of total variants across the billions of basepairs in a specific human’s genome.) Considering that it is unlikely that we will get base editors, ever, which have total error rates approaching 1 in millions, one will have to be a little more clever about how one goes about it. (Maybe some sort of multi-generational mass mutagenesis-editing / screening loop?)
Anyway, I would point out that you can do genome synthesis on a much cheaper scale than whole-genome: whole-chromosome is an obvious intermediate point which would be convenient to swap out. And for polygenic traits, optimizing a single chromosome might push the phenotype out as far as you want to go in a single generation anyway.
If you want to zero out mutational load and create a modal genome, you’re approximately 2 orders of magnitude off in the number of edits you need to do. (The number of evolutionarily-conserved protein-coding regions has little to do with the number of total variants across the billions of basepairs in a specific human’s genome.) Considering that it is unlikely that we will get base editors, ever, which have total error rates approaching 1 in millions, one will have to be a little more clever about how one goes about it. (Maybe some sort of multi-generational mass mutagenesis-editing / screening loop?)
Anyway, I would point out that you can do genome synthesis on a much cheaper scale than whole-genome: whole-chromosome is an obvious intermediate point which would be convenient to swap out. And for polygenic traits, optimizing a single chromosome might push the phenotype out as far as you want to go in a single generation anyway.