I've been wondering about that for the past couple of years, since I heard of CRISPR basically. Who is working on this aspect most seriously right now? Is there any interesting published progress? I understand it will take a while to make real progress, but mostly I'm just curious as an outsider to the industry.
This isn't ready for in vivo use yet due to off-target effects (CAS9 is a very permissive protein that often binds to the wrong part of the DNA).
In the US, Carl June's group at U Penn is working on editing adoptive, engineered CAR T cells for cancer therapy, going into clinical trials. They're probably bummed to have been scooped (first to do an adoptive CRISPR engineered T cell transfer), though their work is certainly more clinically relevant than Lu's.
The problem as I understand it is that right now, CRISPR requires some manual steps in the lab to make it work well. You can design the protein and guide RNA and spacers until you're blue in the face, but if you can't find a specific enough cutting site on the genome, or one that is close enough to your target, or something like that, you'll wind up with a lack of specificity in that cut, which can lead to unwanted mutations. And since the CRISPR system was originally a sort of bacterial immune system, it's really geared towards 'knocking out' specific genes by (I think, but I'm really shaky on this part) introducing a bunch of extra mutations when the cut it makes in the DNA gets repaired. But there are two kinds of repair mechanisms, and apparently there's a way to encourage the more accurate one, although this is really an area I need to read more about.
Anyways, the technique has also been used to introduce entirely new genes, but I think that involves using modified CRISPR proteins called 'nickase's to make single-stranded cuts in the DNA, rather than double-stranded ones. You introduce plasmid DNA with your genes to match up with the cleavage sites, and ideally it gets taken up.
Whatever the approach, you still aren't going to get 100% expression or transfection, and stable transfection either requires invasive techniques like biolistics (shooting DNA through membranes on accelerated nanoparticles) or delivery by viruses, which has a lot of potential, comparatively minimal side effects, and can even be targeted somewhat to certain types of cells. But I think the FDA is nervous about, especially in humans.
Again though, I'm a layman here too, so someone please correct me where I'm wrong :)
The poison is a bicyclic polypeptide that shuts down ribosomes in your liver. Destroying or removing the poison is as difficult as destroying or removing all the protein. (like dealing with mad cow prions) It's just not going to happen unless you like your mushrooms charred pure black all the way through. Well, that or dusty white ash.
Just half a mushroom will kill an adult human. This isn't something to take chances with.
I am not a biologist, but nevertheless I found out something interesting today regarding the problem of designing good guide RNA via machine learning.
The work that I learnt about today addresses 2 key questions via machine learning approaches: off-target effects of CRISPR (http://biorxiv.org/content/early/2016/10/05/078253) and optimization of the guide RNA sequence to maximize on-target activity and minimize off target effects (http://www.nature.com/nbt/journal/v34/n2/full/nbt.3437.html).
I learnt of this stuff from one of the authors who works at MSR New England (http://nicolofusi.com/).
Also of possible interest is their project page https://www.microsoft.com/en-us/research/project/crispr/, where they are planning to release a cloud-based service for end-to-end guide design by incorporating the approaches developed in the above work.
You are completely correct, in fact one thing that was notable about it was how much work intensive it is, she was forced to miss lots of family events because she had to go in the lab work on the cells, it requires lots and lots of manual labor.
That said, the stuff IS awesome, after you figure how to get it right, it can get right a lot. (but she did this with animals, where she CAN attempt trial and error until she figures the right reference gene sequence to use to guide the proteins, I dunno how that would work when you are racing against time to save a live patient for example, specially if you want to edit his heart or some other area that is hard to access).
By the way, one of the motivations of MIT new variations of CRISPR (that don't use Cas9) is that Cas9 technique require big needles if you want to work in a living organism, the new ones would allow you to use much smaller needles, that are more practical to stab into a patient... and it is very forward thinking, because people didn't even tried stabbing CRISPR needles into someone yet, it is just that MIT guys realized it would be impractical with Cas9 and decided to invent another technique before actually trying it.