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Generally speaking:

- Delivery: getting the mRNA and guide RNA into the target cells

- Expression: ensuring the target cell expresses the mRNA, thus making the protein

- On Target Editing Efficiency: ensuring the intended edit happens at a high rate

- Off Target Editing: ensuring other edits in other locations do not occur

There is still time, we are very, very far away from "we can genetically modify everything".

I got some great advice when I first started coding / CS classes. "Skip Eclipse, use Dr. Java. Skip the intellisense and autocomplete at first so you can really learn". I've kept that mindset for all of my coursework and career. It has probably been the most impactful thing for my career. These AI assistants are the antithesis of this idea. Learn your tools and your codebase deeply, the easy things will be so easy you won't need the AI, the impossible things the AI could never do will be possible.

Thank you very much for sharing these links, a SNP id and browser link was exactly what I was looking for!

> What's the risk of lab leak? I think you are latching onto the whole Sars-Cov2 concept here, but it is really a completely different situation. These lipid nanoparticles are highly unstable and require freezing, careful handling, etc. They include no amount of self replication machinery (nor any coded instructions for said machinery). There is nothing to "leak" per say. I am confident that the paper includes the specific formulations of lipids used, as well as the sequence of the payload (were it open access we could confirm).

> Can these particles go airborne? Again, "go airborne" is a common fear with viruses. Can they mutate and gain some new function allowing them to be infectious via a new pathway. These lipid particles wont "go airborne" because they don't reproduce, they are under 0 evolutionary pressure and carry a minimal payload. It like asking if the COVID vaccine could mutate and go airborne. One could certainly spray some of these particles in the air, they will land on the nearest surface and likely break or degrade along the way. You could probably spray them on your arm and it would not result in any editing.

> If someone used them maliciously would anyone even figure it out? If someone were able to successfully deploy a targeted genetic weapon with adverse side effects, it would likely take some time to figure out, but we absolutely have the ability and technology to figure it out today. The result would be a brand new variant in the population which has never been seen before, that looks like a CRISPR edit and is making a bunch of people of one country sick.

> Has everyone involved on this project been working in a lab that has made it near impossible for this to be abused and have all these people gone through exhaustive background and psychological testing and re-testing? Almost certainly not. You are setting a bar pretty high for people doing pretty basic research in mice. I think we should probably setup this level of testing for all our police, military, elected officials, etc.

Citation 3 is the only one worth engaging with, and it answers most of these questions in the summary. Basically the tech is nowhere near ready (despite what some PLA general wants to pretend), and even if it was the actual targeting of a specific population is not even feasible given population genetics.

I think you might be over estimating how effective these technologies are. Even in the most controlled circumstances, the amount of actual specific editing which occurs is probably quite low. Off target edits are likely also occuring. The focus for gene editing currently is on terminal and generally low quality of life diseases, as the low efficacy and high risk are more acceptable. We are many years out from robust and stable editing using a delivery system like this in an ideal clinic environment. Weaponizing this technology in any meaningful way is not something we probably will have to worry about in our life time. The paper is not open access so we can't know for sure what exactly they did, but it is in mice and seems to have a florescant read out, which suggests a rather crude edit (did we chop up the gene enough to turn the lights off).

Hop on the slack, there are plenty of folks (myself included) who are happy to help get you started. I found prefect after slogging through a year of painful development work on an Airflow project, and I have been a rabid fan of it ever since. Been using it at my current gig for 2+ years, on an old version of the open source offering. Despite all that it's been a dream to work with.

Your answer is much better

With DNA sequencing?

Sure, feel free to drop me am email at kylem at mammothbiosci.com

Yes! Thank you!