2007, bacteria used to make yogurt showed that these odd clusters actually served a vital function

12-27-2018    Clustered Regularly Interspaced Short Palindromic Repeats—or CRISPR.  (in a gene)

Yet the function of these CRISPR sequences was mostly a mystery until 2007 when food scientists studying the Streptococcus bacteria used to make yogurt showed that these odd clusters actually served a vital function:  they’re part of the bacteria’s immune system.

See, bacteria are under constant assault from viruses, so they produce enzymes to fight off viral infections.  Whenever a bacterium’s enzymes manage to kill off an invading virus, other little enzymes will come along, scoop up the remains of the virus’s genetic code and cut it into tiny bits.  The enzymes then store those fragments in CRISPR spaces in the bacterium’s own genome.

Now comes the clever part:  CRISPR spaces act as a rogue’s gallery for viruses, and bacteria use the genetic information stored in these spaces to fend off future attacks.  https://www.vox.com/2018/7/23/17594864/crispr-cas9-gene-editing

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11-20-2008 

 Above, imagine the human flu virus RNA is in blue and the bird flu is in red.  Their RNAs are very similar except for a couple of spots.  These differences make a bird flu able to infect a bird.  And a human flu a human.

I have marked one of these differences with an asterisk.  Notice that the rest of the regions are very similar. The similar regions can line up and recombine at the black X's, resulting in something like this at the bottom.

If the recombination pops the right regions from the human flu virus to the bird virus, we get a bird virus that can easily infect people!  -Julia Oh, Stanford

https://genetics.thetech.org/ask/ask290

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11-24-2018  Scientists can now make it so any gene they want can easily spread through a wild population of plants or animals.  Used in the right wa, this technology, called gene drives, might save millions of human lives.

But if something goes wrong, a tool this powerful could be very dangerous.  We need to be very choosy in deciding where to use it….

Another important safeguard is to make sure you can erase any changes you’ve made. You never know what will happen once these things are released into the wild so you want to be able to get rid of it.  https://genetics.thetech.org/driving-genes-wild

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5-4-2016   CRISPR is a game changing DNA editing tool that has already revolutionized biology and may be set to do the same for medicine.  It is a game changer.

What makes it such a breakthrough is how easy it is to program it to go to a specific spot in a cell’s DNA (its genome).  This is quite a feat given that the right spot is somewhere in the six feet of 6 billion microscopic DNA letters scrunched together inside of a microscopic cell.

For the last few years scientists have created tools that let them edit the DNA in the same way but redirecting them to a new DNA target is much harder than with CRISPR. This is the first system where getting to the right spot is almost trivial.

Think about it like a UPS truck.  With the old systems you had to essentially rebuild the mapping system each time you wanted to deliver a new package.  With CRISPR you just enter the new address into the mapping app and bam, you get to the right place.

Once you get past targeting, all of these tools edit DNA in essentially the same way. They all cut the DNA and then let the cell deal with that cut.

Sometimes the cell messes up the gene as it tries to deal with that cut but occasionally, if you add a piece of DNA to the cell that has the edit you want to make, the gene gets edited in the right way.  It is that word “occasionally” that makes CRIPSR a much more powerful tool for basic science rather than curing genetic diseases directly.

See, in basic biology if just a few cells get the DNA change you want that is OK.  You can separate them from the other cells and just use them.  After growing these altered cells for a while you’ll end up with plenty of cells with the changed DNA.

You can even do this with a whole animal. You might use CRISPR on a bunch of fertilized eggs and only use the ones that got the change.  Or if only some of the cells in the animal got the edited DNA, you can mate the animal and pick the offspring that have the change in every cell.

This approach won’t work with most medical treatments though--changing the DNA in just a few cells in patients may not affect their health in any meaningful way.  For example, fixing the DNA mutation that leads to cystic fibrosis in less than 1% of lung cells is simply not going to help a lot. (Diseases of the blood may be an exception because they can be removed easily and added back.)

This is why the next step in making CRISPR ready for treating genetic diseases is to boost its editing efficiency.  We want more cells to have the changed DNA from the very beginning.  And this isn’t the only part we want to improve either.  It would also be nice if we could make it better at targeting. 

The CRISPR system is amazingly good at getting to the right spot in the DNA but it isn’t perfect.  Sometimes it changes DNA where it shouldn’t.  These “off-target” effects can have serious consequences like causing a new genetic disease.  Obviously we want to avoid that as much as possible!

So the CRISPR system is amazing enough to transform biology but not yet perfect.  With a few improvements it may just allow us to finally cure some deadly genetic diseases.  And once these improvements are made, hopefully we will use this powerful new tool wisely. …   -Dr. Barry Starr, Stanford    https://genetics.thetech.org/ask-a-geneticist/why-crispr-revolutionary-and-how-it-works