Can someone explain?
CRISPR refers to the kind of DNA site that can be targeted for cleavage, while CAS9 is a protein that, paired with an RNA matching that site, can cleave wherever it encounters a matching sequence.
I think these guys are pairing a variation of the CRISPR approach with a laser. They pre-bond with the DNA, but the actual cleavage occurs when they shine a laser at the right frequency at the site. That lets them decide when and where on the DNA strand cleavage happens.
If anyone understands this better than me, I'd appreciate any corrections to my explanation ;P
The RNA guide (sgRNA) is chemically caged here, so it has some molecular decorations that are removed with light. The sgRNA can't fully match the underlying DNA it's recognizing until those decorations have been removed with the laser, at which point Cas9 then cleaves the DNA strand.
Think of the sgRNA like a regex pattern. Cas9 is like the regex engine here (but instead of capturing a group, it cuts the sequence), and DNA is the search space. In this system, we essentially have a full match, and Cas9 is in position (having found the match) but it can't cleave yet, because the decorations are blocking the way. As soon as the decorations are removed by light, the sgRNA can move down into a full match, and Cas9 then cleaves.
The primary benefit here is that you can temporally synchronize Cas9. In standard systems, you introduce Cas9 into the cell, and you have no control over when it performs cleavage, since it's essentially a greedy cleavage mechanism - as soon as it finds a match, it cleaves.
This system basically introduces a semaphore, so that you introduce Cas9, allow it find a match and pause. You can then signal for cleavage to begin. As stated in the abstract, this is useful for e.g. studying the kinetics of DNA repair, since you can control when DNA damage (Cas9 cleavage) is happening.
1) It binds to DNA based on where a template RNA strand matches DNA in a genome. That RNA strand has 2 pieces - a piece that attaches to the Cas9, and a piece that matches whatever sequence of DNA you want to bind.
2) It cuts the DNA it has bound to.
(The first property is very special to Cas9. The second property is actually pretty common. The common intention in using Cas9 is to cut DNA at a place that needs editing and hope the cell's own repair machinery fix it properly.)
Important to understand about biology/chemistry, things rarely happen "IFF and only IF", but more often, happen at a rate (i.e. 1 event per microsecond).
So better more true functions of Cas9 are actually:
1) Cas9 spends a larger fraction of time near its target sequence than it does around random sequences.
2) Cas9 cuts DNA ever 1/N timeperiods, and that might be sped up when it is attached to DNA.
So Cas9 should hang out around its target sequence, most of the time, and that the cutting event happens relatively randomly. So _in general_ Cas9 will cut at its site of interest, however, it will also cut elsewhere, purely statistically speaking. And if you want to be guaranteed a cut at your spot of interest, you're likely to get cuts elsewhere ("off-target" cuts to DNA. These are undesired as you really don't want random changes to your DNA that you're not asking for...).
----- now comes the paper -----
If you make it so Cas9 cannot cut because the homing device is kinda kinked or boxy or otherwise not quite right (but it is still able to home in on particular sequences of DNA), you can make it so Cas9 runs around and finds where its supposed to be, but just hangs out there; Function 1 still works, but function 2 is turned off. These scientists made a special version of RNA that only permits the Cas9 to work when light is shined. So the RNA absorbs the light from a laser, breaks a seal, and the Cas9 snips right then and only then (in a matter of seconds). And any Cas9 molecules that did not get light cannot cut - they just continue to hang out and don't do any damage that they otherwise might do, statistically.
If you're trying to cut a specific sequence and only a specific sequence, this increases the statistical chance you are correct by shortening the time period (and spatial localization) when Cas9 can actually take its second, cutting action.
So before, if you want to study/control the processes that go on after that cut, you'd be a bit out of luck since you didn't know when the cut would happen to start experimenting, it would be a hard messy problem. Now, you can just trigger the cut to happen right when you're ready for it.