I don't think the 'technique' is settled enough to have an answer to your question yet. There are a lot of different 'errors' that can happen, each of which has entire sections of researchers working to ameliorate them.
The floor to error is that a wild-type Cas9 protein with a naively generated guide RNA, and a payload DNA along with it, just dropped into a petri-dish of cells correctly edits some single-digit percent of cells. That's the crudest of experiments a grad student might do on their first try. And that it is that robust (in a biological laboratory) is precisely why it is so powerful. Single-digit percent activity on an unoptimized first try is actually pretty amazing in the context of biology.
Thanks, that's helpful to know. I'm actually thinking about within the context of that edit of the cells. Is it a binary thing where either the cell is edited or it isn't, or can we have an edit with some error rate in regards to what actually was pasted in? The cutting seems highly specific, you need some sort of homology between your guide RNA and the target sequence, right? It's the pasting I'm mainly curious about.
All the pop science articles seem to make it out to be a flawless system, and the engineer in me is highly skeptical of that narrative.
The cutting is mostly specific (given you have a reasonable target sequence - a pure 'GGGGGGGGGGGGGG' sequence is just chemically problematic anyway).
The cutting splits the DNA in half completely. It has to rejoin itself (by a not-well understood mechanism termed 'NHEJ'). This rejoining of the DNA is the kind of 'well it works (mostly, sometimes!)' part that is actively being better understood. Cas9 really has no relevance to this part of the process - unless it is used as a platform to attach DNA-repair machinery onto.
Like in all things biology, concentration and time matter. So if you leave Cas9 on 24/7 at very high concentrations with nothing to do, it will go ahead and cut all over the place. The goal is now to bring to bear everything else we know about biological expression to put the Cas9 homing system in its place, only when it should be in place. We already know pretty good mechanisms to make sure Cas9 only turns on under certain conditions, at certain times, is inhibited under other conditions, is otherwise made even more specific. Those are engineering 'details' at this point. And by 'details' I mean you have a huge academic and corporate effort underway currently figuring out how most efficiently and most accurately control Cas9's function.
Common results with a naive wild-type Cas9 (which we have moved on from in a lot of ways):
There are also very powerful uses for Cas9 that do not cleave DNA at all. Sticking a gigantic 'BREAK()' command onto Cas9 (that cannot cut DNA) can be very useful where the natural break command has been lost.
I've worked on this exact problem before.
There are two kinds of possible errors:
1. On site errors- small errors that occur at the spot you intended to edit. Occur maybe 30% of the time- usually will not break anything, but worth thinking about. What we know so far is that these are not random and it will be possible to rationally design crispr sequences to reduce (or even purposefully cause) specific on site errors.
2. Off target errors- this is when Cas9 cuts the genome at the wrong spot- this is the main error people are worried about. Computational efforts in guide design have attempted to reduce this, and will get more advanced as we learn more about the binding kinetics of Cas9. These also occur non-randomly, at highly quantifiable frequencies, and are due to biophysical rules. Also, newly discovered and engineered Cas variants have substantially better specificity and will work to further reduce this problem. Also off target effects are usually not problematic and can be tested for (will be bred out of crispr-ed crops)- however, if you're going to do CRISPR in live humans it is likely that regulatory bodies will require a demonstrated very low probability of off target effects.
Basically, errors are an issue to spend a lot of time thinking about when designing a crispr system intended as a human therapeutic. For most scientists, however, errors are not terribly important or common and they don't need anything beyond a bit of rational guide design for their experiments.
The floor to error is that a wild-type Cas9 protein with a naively generated guide RNA, and a payload DNA along with it, just dropped into a petri-dish of cells correctly edits some single-digit percent of cells. That's the crudest of experiments a grad student might do on their first try. And that it is that robust (in a biological laboratory) is precisely why it is so powerful. Single-digit percent activity on an unoptimized first try is actually pretty amazing in the context of biology.