Assembled DNA with a different backbone seems readable by cell machinery

February 9, 2014 2:27 PM

Much easier to put together custom DNA An interdisciplinary study led by Dr Ali Tavassoli, a Reader in chemical biology at the University of Southampton, has shown for the first time that 'click chemistry' can be used to assemble DNA that is functional in human cells, which paves the way for a purely chemical method for gene synthesis. Writing in Angewandte Chemie International Edition Dr Tavassoli's team and his collaborators, Dr Jeremy Blaydes and Professor Tom Brown, show that human cells can still read through strands of DNA correctly despite being stitched together using a linker not found in nature.
posted by aleph (17 comments total)

The description is a little off, since it's been possible to synthesize DNA chemically for years. The advance seems mostly to be that this is a purely chemical way to synthesize long pieces of DNA, which previously had to use a mixture of synthetic chemistry and enzymatic steps.
posted by pombe at 2:31 PM on February 9, 2014 [2 favorites]

Pombe has it; useful for gene synthesis by linking together lots of short strands.

Please don't use press releases from the originating institution. This is neat work, but NOT that revolutionary; all kinds of linkers can be read by transcriptional machinery. The neat thing is that "click" chemistry is very fast and high yielding, and SOME click chemistry (not this one) "orthogonal" - in other words, uses a reactivity profile - that is compatible with many of the thousands of chemical funnctionalities present in DNA and other biomolecules. The click chemistry they use here aint happy in vivo, but once the links are formed, then they are perfectly stable and happy.

In the pipeline has a soberer analyses - in particular read about the weakness of their assays and the fact that is is one link.
posted by lalochezia at 2:33 PM on February 9, 2014 [6 favorites]

Thanks for the link lalochezia! *Much* better description.
posted by aleph at 2:46 PM on February 9, 2014

Here's the Wikipedia entry on click chemistry for those who, like myself, wondered what the hell that is.
posted by Ivan Fyodorovich at 3:00 PM on February 9, 2014 [2 favorites]

It may be old hat if you're in the know, but if this is the first you're hearing about any of this it still seems pretty cool.



Metafilter:
posted by bleep at 4:20 PM on February 9, 2014

After reading all the links, this is the conversation I kept hearing in my head.
posted by valkane at 5:07 PM on February 9, 2014 [1 favorite]

Fantastic post, BTW. Thanks aleph!
posted by valkane at 5:16 PM on February 9, 2014

I, for one, welcome our new helical overlords.
posted by STFUDonnie at 7:13 PM on February 9, 2014

Roy Batty approves of this press release.
posted by CosmicRayCharles at 8:10 PM on February 9, 2014

I was under the impression that DNA expressed some of its information via folding patterns and distances in 3D space between otherwise distant sequences.

Surely different chemistry would destroy or alter this information?
posted by effugas at 8:14 PM on February 9, 2014

Yay!

Wait, how will this kill us?
posted by codswallop at 9:00 PM on February 9, 2014 [1 favorite]

I've heard that scientists who study genetics are referred to as Gene Junkies because they have such a passion for the subject.
Had to say I enjoyed reading the main link, lalochezia's link was to technical for a layman like me.
posted by Narrative_Historian at 1:39 AM on February 10, 2014

I was under the impression that DNA expressed some of its information via folding patterns and distances in 3D space between otherwise distant sequences.

Surely different chemistry would destroy or alter this information?


Yes and no. There are lots of subtle conformational (read: folding shape) effects with DNA. However for a storage of information for simple transcription (=enzymes reading the code to make proteins in an on/off way - no "transcriptional control*") all the DNA has to do is be able to display A,G,C, & T in a string in the correct order with the links between the bases (which this paper is a new example of) suitably similar to phosphate that the transcpritional machinery (enzymes that copy DNA ->RNA) can ignore this new link.

The subtle change that this 1 link per 100-200 bases has on transcription is probably negligible; however if ther was a big gene made with dozens or hundreds of these links in millions of bases we might see the complex effects you are referring to kick in.


Long run on sentences....something something read length biology joke something something.


* A complex topic that I am woefully undereducated about.

posted by lalochezia at 6:03 AM on February 10, 2014 [1 favorite]

Often biochemists and molecular biologists would like to synthesize a long piece of DNA, chemically or otherwise, and not worry (too much) about the secondary structure until they have it in a different host or expression vector.

This isn't entirely accurate, but I tend to think of the DNA as the program code and the epigenetics as the file permissions. I guess the secondary structure would be... making file dependencies? Heh. I'm not sure. This work too falls between the gaps in my metaphor - I don't have the CS background for it, I've forgotten whatever I once knew about compilers - but it's closer to making sure your program can be ported to other systems. That other system may not have all the files you need to run the program correctly, but you want to see that it's still an executable and not just garbage.
posted by maryr at 7:31 AM on February 10, 2014

Long run on sentences....something something read length biology joke something something.

Nonsense.
posted by maryr at 7:32 AM on February 10, 2014 [1 favorite]

Code-on!
posted by lalochezia at 10:14 AM on February 10, 2014

Oh, stop.
posted by maryr at 6:53 PM on February 10, 2014