So-and-so gives the following idea: Synthesize a chunk of DNA at the limit of what we can currently do—on the order of 1Mb. Choose the sequence so as to replace some chunk of a human chromosome, and to have lots of target variants. Then, somehow integrate this chunk into the genome of a reproductive cell (gamete, zygote, etc.).
IDK how you’d do the integration—but it might doable, e.g. with two DSBs. I.e. a really really big CRISPR edit. (Or something about transposons that I didn’t understand?)
IDK how much this would disrupt the epigenomic state. You could probably avoid hitting many sex-linked imprinting regions, but the state of synthesized DNA might be otherwise weird—though it’s not that much DNA so maybe it would be fine.
The fun question is, how much effect you can have? On a really naive model, if there’s only 10 or 20 relevant regions on each chromosome, you’re probably only getting 1 or 2 per 1Mb window. However, relevant regions will be concentrated away from centromeres and telomeres. Further, relevant regions will be somewhat randomly placed, rather than uniformly placed (I assume). So there should be a lot of variance in how many relevant regions show up in any given 1Mb window. An interesting math problem.
So-and-so gives the following idea: Synthesize a chunk of DNA at the limit of what we can currently do—on the order of 1Mb. Choose the sequence so as to replace some chunk of a human chromosome, and to have lots of target variants. Then, somehow integrate this chunk into the genome of a reproductive cell (gamete, zygote, etc.).
IDK how you’d do the integration—but it might doable, e.g. with two DSBs. I.e. a really really big CRISPR edit. (Or something about transposons that I didn’t understand?)
IDK how much this would disrupt the epigenomic state. You could probably avoid hitting many sex-linked imprinting regions, but the state of synthesized DNA might be otherwise weird—though it’s not that much DNA so maybe it would be fine.
The fun question is, how much effect you can have? On a really naive model, if there’s only 10 or 20 relevant regions on each chromosome, you’re probably only getting 1 or 2 per 1Mb window. However, relevant regions will be concentrated away from centromeres and telomeres. Further, relevant regions will be somewhat randomly placed, rather than uniformly placed (I assume). So there should be a lot of variance in how many relevant regions show up in any given 1Mb window. An interesting math problem.