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ZincFinger

06/11/11 8:46 PM

#24025 RE: shannonwm #24014

When you talk about how well zinc fingers work it depends on who is using them: If SGMO (or SIAL who uses SGMO's technology) extremely well. Others not so:

The basic situation with zinc fingers is this (sorry but you have to understand a bit to know what's going on):

Zinc fingers work analogously to a lock mechanism

(Note to Mojo: this is an analogy and not meant to be taken literally. If you have trouble with the word try wiktionary.org. I know that one is a biochemical and the other is mechanical. It's an a n a l o g y)

where a zinc finger is analogous to a pin in a lock mechanism. The more pins (or zinc fingers) you use, the more secure the lock (or in the case of zinc fingers the lower the probability that it will fit the wrong lock just by chance.)

18 zinc fingers is about what it takes to insure that they will code for a given desired location in the genome and for no other location (you don't want any changes in undesired locations. Such undesired changes are what all other methods of genetic modification do and what makes them so ineffective.)

It sounds simple: just keep a library of each of the possible single zinc fingers (like movable type)and you can readilly assemble any desired 18 zinc finger set from them.

Unfortunately there is a huge catch that stopped progress on zinc fingers until Sangamo Biosciences figured a way around it: the great majority of combinations of zinc fingers just don't work: the individual fingers "clash" or "conflict" with each other. Nature's solution is to have a number of different zinc fingers to correspond to each neucleotide (the unit of DNA that they "key" to ). That horrendously complicates the situation because the possible variations is immense and no one had a practical way to sort out the very small percentage that would work (i.e.: the individual finges in a set would work well together).

SGMO broke the logjam by realizing that zinc fingers that worked together did so in triplets. So they created a library of triplets that worked well together from which a working set of 18 could be assembled (actually that's still a simplification, but it gives the general idea). Plus SGMO developed a computer program to sort out which triplets worked well together (triplets have the same problem!) So SGMO can take a genetic sequence and let its comuter program sort out which triplets can be used to construct it in a combination that will work well together. No one but SGMO can do it that fast efficient and effective way.

All others use trial and error: you make a LOT of zinc fingers and test them. Requires a lot of time and money and lab people and, because you can only test a very small subset of the possibilties (and only SGMO has the program to sort out the best out of ALL possiblities) you have to be satisfied more often than not with ones that work "after a fashion" if at all.

So some scientists may have had poor results with zinc fingers. BUt that says nothing about SGMO and SIAL's zinc fingers. Theirs are the ones that work. Sorry to make it so complicated but that's how science is a lot of the time!

I had to tell you all that so you'd know that if you saw something saying that someone had used zinc fingers with poor results it was no reflection of SGMO/SIALs zinc fingers which are in an entirely different category.

PS (and OT) I do appreciate Mojo's perspective on the rare occasions when he actually offers one. Different perspectives are useful. Empty posturing and distortions of analogies into something else etc are not.