the error rate on cutting is low enough that "it is no longer the issue". CRISPR is not the whole story for any given genetic manipulation project. Here's generally how it works:
1) cut DNA (this is the part that CRISPR does)
2) add replacement DNA
3) kill everything that doesn't have the replacement DNA in there
4) optional: repeat the process to 'clean up' your modification [0]
Basically in the pre-CRISPR era, if you, say, wanted to make a transgenic mouse, you had to take some embryonic mouse stem cells and just add DNA and hope that it found its way into the "right place". If you were adding a totally new gene - usually not a big deal because you kind of don't care where it winds up, shoot first, do your experiment, ask questions later.
If you were knocking out or replacing a gene, (aka specific location addressing) it is a big deal. Suddenly step 3), while necessary, is not sufficient to guarantee successful DNA modification. Furthermore "checking" is really hard, You need to implant the modified stem cell into a mouse embryo, create a chimeric mouse (a mouse that has cells from two genomes), hope to hell that the cell you implanted into the embryo randomly got chosen to turn into an ovary, and then take the children of the mice which should have the gene modification. And then you check the genome of the mice and it turns out that it's all wrong and you have to start from scratch (literally had a friend who unluckily spent the first 5 years of grad school repeating this process about 10 times IIRC). This gets really complicated when step 1) is inefficient, or cuts in the wrong place, or has a spontaneous integration preferentially in the wrong place - you off the bat take a huge hit (a hit on the order of 90%, if you were lucky).
With CRISPR, you basically derisk step 1), pushing the 'hard part' of molecular biology elsewhere. Suddenly your step 3) selections instead of being a low-yield, probabilistic crapshoot, are near-quantitatively correct. Since it's also the first step, suddenly the one or two 'actually hard' parts of molecular biology, like in the case of the mice the complicated process of generating chimerics, etc, can really be tackled head on by sheer numbers much more easily.
[0] in order to do 3) you usually need some extra stuff (resistance genes) that you might not want in your 'final work', so you might have to come up with a second stage to 'clean this up'.
Keep in mind that Church and Mukherjee have not really ever 'been in the trenches' actually doing these things (church was a structural biochemist and later a yeast geneticist - yeast are easy peasy). Their grad students and postdocs have.
1) cut DNA (this is the part that CRISPR does)
2) add replacement DNA
3) kill everything that doesn't have the replacement DNA in there
4) optional: repeat the process to 'clean up' your modification [0]
Basically in the pre-CRISPR era, if you, say, wanted to make a transgenic mouse, you had to take some embryonic mouse stem cells and just add DNA and hope that it found its way into the "right place". If you were adding a totally new gene - usually not a big deal because you kind of don't care where it winds up, shoot first, do your experiment, ask questions later.
If you were knocking out or replacing a gene, (aka specific location addressing) it is a big deal. Suddenly step 3), while necessary, is not sufficient to guarantee successful DNA modification. Furthermore "checking" is really hard, You need to implant the modified stem cell into a mouse embryo, create a chimeric mouse (a mouse that has cells from two genomes), hope to hell that the cell you implanted into the embryo randomly got chosen to turn into an ovary, and then take the children of the mice which should have the gene modification. And then you check the genome of the mice and it turns out that it's all wrong and you have to start from scratch (literally had a friend who unluckily spent the first 5 years of grad school repeating this process about 10 times IIRC). This gets really complicated when step 1) is inefficient, or cuts in the wrong place, or has a spontaneous integration preferentially in the wrong place - you off the bat take a huge hit (a hit on the order of 90%, if you were lucky).
With CRISPR, you basically derisk step 1), pushing the 'hard part' of molecular biology elsewhere. Suddenly your step 3) selections instead of being a low-yield, probabilistic crapshoot, are near-quantitatively correct. Since it's also the first step, suddenly the one or two 'actually hard' parts of molecular biology, like in the case of the mice the complicated process of generating chimerics, etc, can really be tackled head on by sheer numbers much more easily.
[0] in order to do 3) you usually need some extra stuff (resistance genes) that you might not want in your 'final work', so you might have to come up with a second stage to 'clean this up'.
Keep in mind that Church and Mukherjee have not really ever 'been in the trenches' actually doing these things (church was a structural biochemist and later a yeast geneticist - yeast are easy peasy). Their grad students and postdocs have.