RE: [asa] writing DNA...

From: Dehler, Bernie <bernie.dehler@intel.com>
Date: Fri Sep 26 2008 - 19:49:28 EDT

Hi Preston- just curious- when do you think the technology was

available to first do this?

...Bernie

---------------------------------------

If you mean the technology to synthesize and assemble DNA, it began

in the early 70s with the capacity to make snippets of a few bases

synthesized in a series of reactions done manually. Automated

synthesizers using various linking chemistries were developed

commercially a few years later, and the length of segment the

machines could make reliably increased up to over 100 bases by the

mid-to-late-80s, if memory serves.

That is how DNA is routinely made today for targeted mutagenesis and

short sequence construction. This is a basic skill in any mol. biol.

lab. To make longer sequences, you make overlapping complementary

fragments, hybridize them by temperature annealing in solution and

then link the ends with the enzyme DNA ligase. You can also use PCR

to make larger sequences starting from shorter sequences. At some

point you attach sequences that enable the whole thing to be

replicated in bacteria and put it in the bugs ("cloning") to make

larger amounts of it.

There isn't any need in most labs to synthesize large sequences from

scratch - you are usually more interested in modifying and combining

natural sequences to get what you want. However, if you need to make

a large number of changes over substantial distances in the sequence,

it can become more efficient to just make it from scratch.

The methods for assembling the small fragments into very large

molecules like Venter has done have just been developed in the last

few years - that's why it's news. I think this is the first synthesis

at the scale of a small cellular genome. Increasingly larger viral

genomes have been done to work up to this. I don't know the details

of how they have done this - I'm sure they've developed very clever

ways of dealing with the problems you have efficiently assembling

these very large molecules. The question now is, can you get the

giant molecule into the bugs and get them to adopt it as their new

chromosome? I think it will work. Since DNA transformation was

discovered back in the 20s, the bugs have done everything we've asked

them to.

I guess you got the fire hose. ;)

Preston

------------------

Wow- sounds pretty amazing- thanks.

I like following Venter news because he's claiming to create new things by writing DNA. He seems very ambitious and out-front in all this. Are there other people/groups pioneering (writing DNA) like himself? Let me know, so I can add them to my "watch list?" I'm not really aware of his competition.

...Bernie

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Received on Fri Sep 26 19:49:52 2008

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