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Comment by koeng | Hacker News Reader

Here is the paper link - https://doi.org/10.1016/j.molcel.2021.08.008

They did a lot of hard work to get there! A few years we synthesized some prokaryotic argonaute proteins for their lab. Bet they were considering them as an alternative to CRISPR proteins. Excited to use CasMINI in some bacterial systems, Cas9/Cpf1 are kinda annoying to synthesize.

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And thats why I love HN, some topic with notation I have no idea about but I my ADHD will solve that for sure. Thanks for providing the entrypoint!

An important detail left out from the short article is that CasMINI was evaluated for base editing as well. I personally would hesitate taking something that cuts my DNA unless I really really need to and close to dying, but I might accept the risks of base editing if it gives me significant health benefits.

I am surprised by your comment. We have much better techniques for understanding off-target issues with DSB-inducing gene editors. I'm certain the tox package $NTLA put together to support NTLA-2001 looked into this non-clinically very, very closely.

From my vantage point, $BEAM does not have the analytical tools to actually know where edits are occurring in an entire genome-context. Maybe RCA-type ideas, or super deep NGS, but I haven't seen robust and convincing off-target analysis yet.

I don't have enough biological knowledge to understand the potential off-target effects of current base editing technology at $BEAM, and I accept your opinion that it's not yet ready for production, but in general what I love about base editing is that there are billions of people living as control / experiment groups, so as long as the off-target effects can be understood and minimized (hopefully in a few years), I don't have to worry too much about the main effect too much.

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