The title in Nature: “Programmable base editing of A•T to G•C in genomic DNA without DNA cleavage”<p>A brief description of what was accomplished (a modification of cas9): “We evolved a tRNA adenosine deaminase to operate on DNA when fused to a catalytically impaired CRISPR-Cas9. Extensive directed evolution and protein engineering resulted in seventh-generation ABEs (e.g., ABE7.10), that convert target A•T to G•C base pairs efficiently (~50% in human cells) with very high product purity (typically ≥ 99.9%) and very low rates of indels (typically ≤ 0.1%).“<p>Translation: they modified the CRISPR <i>associated</i> DNA editing enzyme, cas9, to “deaminate” (remove or otherwise alter the amino groups) in A-T or G-C pairs without breaking the DNA, as cas9 normally would.<p>This makes single point precision edits possible, but I’m not sure what that implies for the “guide RNA” cas9 needs to know where to make the edits, as I haven’t read the paper in full yet.
While direct editing of bases will be a really useful tool, I think it's worth pointing out to any alarmists about human editing that our ability to make directed changes far outpaces our knowledge of what changes to make (and our ability to make reasonable guesses about how safe those changes are). Although there are a relative handful of diseases that have a single, protein coding change that's responsible (sickle cell, cystic fibrosis, etc), most diseases are due to multiple variants, many of which are non-coding, interacting with environmental factors and chance (diabetes, obesity, depression). These kinds of tools are incredibly useful in the lab for making advances in understanding disease, but we're a long way off from widespread clinical use, if that is even in the cards.
In case an author reads this. I tried getting the data from one of the papers:<p>>"High-throughput sequencing data have been deposited in the
NCBI Sequence Read Archive database under accession code SRP119577"<p><a href="https://www.nature.com/nature/journal/vaap/ncurrent/full/nature24644.html" rel="nofollow">https://www.nature.com/nature/journal/vaap/ncurrent/full/nat...</a><p>It doesn't seem to work (but I haven't used SRA before):<p>>"The following term was not found in SRA: SRP119577."<p><a href="https://www.ncbi.nlm.nih.gov/sra/?term=SRP119577" rel="nofollow">https://www.ncbi.nlm.nih.gov/sra/?term=SRP119577</a>
We've written a short explainer on CRISPR (if you're not familiar with the basics): <a href="https://humbot.io/How-are-designer-babies-made" rel="nofollow">https://humbot.io/How-are-designer-babies-made</a>
Hopefully this is going to be great news. I can't believe how fast the research with CRISPR is moving, and can't wait to see what's next!
How are we claiming to be able to precisely edit DNA when we can’t even properly sequence it all yet - from just a couple days ago: [<a href="https://news.ycombinator.com/item?id=15534325" rel="nofollow">https://news.ycombinator.com/item?id=15534325</a>]?