I used to work in actual gene engineering and understand this topic in great depth.
CRISPR is mostly good for knock-out (inactivation / attenuation of an existing gene) by introducing indels (insertion / deletions) in the middle of gene's coding sequences by breaking the strand with CRISPR, and then relying on a DNA repair mechanism called non-homologous end joining (NHEJ), which is not very precise and hence results in either insertion or deletion of a few nucleotides. It is possible to do knock-ins (introduction of a new gene, or alteration of an existing one) with CRISPR, but it is very difficult and gets increasingly more difficult with the length or insertion difficulty of the sequence you want to insert at. Most notably, if you want to genetically engineer something in a stable and predictable way (you know, to be useful for ANYTHING AT ALL), then you need to typically use positive and negative selection cassettes (cassette in this context is basically a sequence of DNA which contains several components for performing a function - in this case, expressing a protein).

What are these? Positive selection uses cDNA (gene with intronic sequences removed - just has the coding regions) of a gene which allows survival when a toxic agent is incubated with your material of interest (usually an antibiotic of some kind). A typical example is a Neo cassette , which confers resistance to neomycin. Add neomycin to the medium and boom! Only units with your transgene inserted are able to survive. This brings to negative selection. Here you have a cassette which is in your vector (sequence being used to knock the gene in) but outside of your transgene, hence it will only be in the final unit's DNA if the transgene didn't insert correctly. An example of this would be a TK (thymidine kinase from herpes simplex) cassette. This means that you can add something like gancyclovir to the medium and anything which survived the Neomycin due to having the transgene, but with a random insertion containing the TK cassette, will die. Leaving you (ideally) with just the material which has your transgene of interest, correctly inserted. These cassettes are usually flanked with sites like LoxP or FRT so that they can be excised later by incubation with Cre (excises sequence between LoxP) or FLP (excises sequences between FRT). Obviously none of this applies to an RNA virus, but the techniques remain the same, as it is the only way we know how to do it.

But so what?

What this means is that genetic manipulation leaves a fuck tonne of exogenous sequences littered throughout the final material. This is why we can be so sure that COVID-19 is not engineered - there is zero evidence of any engineering sequences in the virus. There are only sequences from existing strains of coronaviruses, plus some mutations in the known mutation-susceptible regions of coronaviruses. The best current theory is that from a very sustained repository of coronaviruses in the bat population, it transferred to pangolins in wildlife markets, and then to humans, where it most likely mutated again to confer it's current hyper-virulence. This is something viruses do.

The idea that it's engineered because "wow it's so spicy" is intellectually empty, and is a basic argument from incredulity.
I hope that was interesting to some of you, but I assume that it won't land anywhere with nbohr, as I'm obviously an agent of the deep state.

I'm off to go and claim my fancy website as payment now.

To begin, I rather liked your technical dissection of what using CRISPR to engineer looks like. Thank you.

That said, all this tells me is that you know the ways that a bio-engineer would look for signs of CRISPR engineering in a sample.

If you were in a clandestine state-sponsored bioweapon program, you would know that other countries and the outside scientific community would
use these measures to identify your work so you would do your best to minimize or avoid the detection.

For example, you might release many different strains of the infection:

(https://www.foxnews.com/science/coronavirus-mutated-at-least-30-different-strains-study-finds)

so that there is plausible deniability if any engineered versions are found:

"Why is your lab the only one who found these manipulations? I think you are cranks or have ulterior motives."

Just to clarify, this is how you validate proper insertion of a knock-in, which CRISPR is not very good at. Usually you'd use homologous recombination (HR) instead (insertion of a sequence with regions complementary to an endogenous sequence, such that it integrates into the DNA during normal replication & repair). CRISPR is being touted as the most amazing thing since sliced bread, but it has major limitations. The aforementioned reliance on NHEJ mediated repair after DNA strand breaks makes it incredibly technically challenging to do any kind of knock-in, with an absolute ceiling on what is practical which is way lower than with HR, plus CRISPR sequence specificity is determined by short guide RNA molecules which can usually bind at numerous different sequences with a host's DNA, meaning you tend to get a lot of off-target indels, as well as the ones you intended. This can be mitigated by using mutant variants of CRISPR such as nickases (only break one DNA strand rather than 2, meaning you can use 2 guide RNAs for your site of interest, dramatically reducing the chance of off-targets), but nickases may not function as efficiently and you can still get off-target effects, just in lower numbers. Still not great when ANY off-target effects can break your experiment, and the only way to determine if you have them is sequencing the entire genome (costly, time-consuming, not guaranteed to give a definitive answer).

So you're saying they


* Discovered SARS-CoV-2
* Decided to bio-engineer additional viruses just like it to be able to gaslight certain researchers at random
* Infected the entire goddamn world to somehow benefit their own country
* ???
* Profit