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Re: igotthemojo post# 28807

Saturday, 08/13/2011 2:16:20 PM

Saturday, August 13, 2011 2:16:20 PM

Post# of 279315
If you knew the science background of zinf fingers you would realize that SIAL's involvement with KBLB is a lot deeper than merely selling zinc fingers. (Read some of my past posts to get a very small indication of how ZFs are more complex than they appear. What I said may seem complex but it's still greatly simplifed.

Zinc fingers have a selective attachment to the nucleotides in DNA (the "letters", A,C,T and G, that make up the "code"). Greatly simplified, a zinc finger will attach to one of the letters and not the others. So a set of zinc fingers acts as an "adderess" by specifying a particular sequence of DNA (string of "letters") So the *simplified* theory is that you can just make up a set of zinc fingers that correspond to the sequence you want to make a change at and attach to the ZFs the sequence you want inserted there and an enzyme to accomplish that (Usually Fok1) and that's it.

If it was that simple everyone would have been using zinc fingers for many years already. But like a lot of science and especially biology, it's a lot more complex than that.

Zinc fingers affect how the other zinc fingers close to them interact with the DNA. So you cannot just take individual zinc fingers to correspond to each of the letters in your sequence and throw them together and expecet them to work as intended.

Think of it like a dinner party: you need to take a bit of care about who sits next to who if you want to avoid "unfortunate" situations (person sitting between his wife and mistress, and right across from his ex, for example).

There are, for each letter of DNA, a LOT of different zinc fingers that will attach to it. The problem is picking out a set of zinc fingers that will work well together. THAT's the big problem that Sangamo Biosciences and no one else has cracked: They figured out that zinc fingers tend to work together in triplets. That very important insight enabled them tow work out a computer algorithm that will compute a good candidate set of ZFs for a particular sequence.

BUT that is still very much a "work in progress": SIAL and SANGAMO are constantly updating and improving the algorithm which means they are highly motivated to work closely with SiAL's customers. Also SIAL tests each new set of ZF's they make before they ever send them out to a customer (so if they don't work well or well enough, they can compute another set)
And THAT is very simplified but should give the general idea.

So if you don't want to bother reading the science you might at least acknowledge that there is a lot going on that you are not aware of and consider that before claiming that something is ridiculous just because you cannot see a reason for it.

Suggestion: Instead of stating that something is ridiculous, try asking if anyone knows a reason. You might get much better responses to your posts with such a change of approach.

RE: zinc fingers success: ZFs still don't work the first attempt evey time. BUT they have worked so far in every species attempted across a wide range of animals and plants, INCLUDING SILKWORMS (I've already posted an abstract of a study in which zinc fingers were tested in silkworms and worked excellently). Naturally SGMO and SIAL want to continue improving the process until they work the FIRST time every time. But don't panic if the ZF GMs KBLB is doing don't work one time (and note that the DID work on the first round.) So if they should fail to work on the first attempt in some future round then consider that a prime opportunity to buy cheap shares from someone who panics because they didn't do their DD. attempt in some future round then consider that a prime opportunity to buy cheap shares from someone who panics because they didn't do their DD.
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