Nope, it's just the Cas9 protein and the guide RNA. The guide tells Cas9 precisely where to make cuts in the DNA. The part that's cut is naturally removed and digested by the cell. Then when that happens, the cell's natural repair mechanism takes the two open ends of DNA and connects them together.

As you might guess there's some work required to figure out dosing. To low of a dose and you probably won't edit enough cells, so the un-cut gene will persist. Too high of a dose and you're probably going to harm the patient or cell.

Right, totally different needs here. I use them for in-vivo gene editing, so purity and precision are paramount.

Like most things out there, when you need super high purity and quality, it's gonna cost you a lot. In this case oligos are already a pain to make so it's ridiculously expensive.

To give you an idea, around 2000mg of the oligo I use as guide RNA will cost in the $2M range.

Correct! In ex vivo applications we really need an insertion mechanism.

For in vivo, there are a lot of diseases we can treat by just knocking out the gene and not inserting anything.

Unfortunately there really isn't much clinical data for in vivo gene editing, the only results so far are from two clinical trials from Intellia Therapeutics. Their results are really promising, but so far they've only shown they can do gene knockout in liver cells, which is pretty limited in scope. Hopefully them and some others are working on other ways to perform gene editing.

Oligos used for CRISPR-Cas9 are extremely expensive. They're usually larger (60-120mer) and have to be much more pure to avoid off target editing.

They're currently one of the biggest bottlenecks in the gene therapy field since we can't make enough of it fast enough and with high enough purity.

I think most answers here are covering the ex vivo CRISPR-Cas9 applications. Just gonna throw in a thought on in vivo since that's what I work on.

As others stated, CRISPR-Cas9 only cleaves and removes DNA, it does not insert new DNA. It does this by using a strand of guide RNA which has a nucleoside sequence matching that of the target DNA site (there's a lot more to that subject as well). This has been done successfully in vivo by Intwllia Therapeutics, there are a few other companies that are beginning to does patients but don't have results yet.

I'm order to insert new DNA, some other tool is needed. But to date, we have not done this in humans! The most promising technology to do this right now is an AAV delivery mechanism.