"DNA Origami" Could Allow For Controlled Drug Delivery 29
esinclair writes "As reported in Nature News, researchers have designed a method which allows DNA strands to be formed into cubes and other designs by oligonucleotides. The uses of this DNA origami are still being developed. One possibility for them is to be used as a drug-delivery system. The fact that scientists have also come up with a method to lock these structures and use 'keys' to unlock them would conceivably allow for a controlled delivery system."
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Does the immune system actually react to extracellular DNA? I've never heard of that happening. Wouldn't be that much of a threat, DNA by itself doesn't do much besides sit there and likely get chewed up by nucleases. But IANAIB (where IB stands for immunobiologist or whatever they call themselves).
Re:Anonymous Coward (Score:4, Informative)
IANAIB (where IB stands for immunobiologist or whatever they call themselves).
Immunologist. And yes, from what the immunology books say, DNA is an antigen that usually avoids detection by being separated from the immune system, like in the cell nucleus. Once it gets out of there, the system says something along the lines of, "Whoa, whoa, whoa. What is this stuff? I've never seen it before, so it must not belong here. Let's destroy it." That's my understanding of it, at least.
I admit that this technology sounds very interesting, but until they come up with a way to encapsulate it, I don't expect to see it actually working in practice... That is, unless they don't need it to stick around very long.
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Yeah, ignorance is a go go! Wooo!!!
Expect DRM to come soon! (Score:5, Funny)
DNA Rights Management... Write your MEP's now!
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Write your MEP's now!
Morphological Equivalent Privacy?
DNA is economical (Score:5, Informative)
However, one of the most relevant issues in biotech and nanotech is the question of cost. The most elegant drug delivery system in the world will never be viable if you can't produce it in decent yields, at a reasonable cost.
My work involves viral capsids, which we use as nano building blocks because they (sometimes) self-assemble, making very large, symmetric structures with relative ease. However, you still have to produce the protein, which usually involves engineering some other organism to produce it for you, since it can't be done synthetically. Assuming that step can be accomplished, you still must purify it, and hope that once all is said and done the protein has retained the appropriate structure. If it's been "deformed" along the way, it's usually a one-way street, and your precious product is now garbage.
In contrast, DNA can be made more or less fully synthetically, and the misfolding problem is a non-issue: it can be melted down and re-folded nearly infinitely.
Those features make DNA really interesting as a better candidate for commercially-viable nanotech. On the other hand, DNA is going to be uniformly negatively charged everywhere, as opposed to proteins which can take on nearly any characteristic you might want, due to the range of amino acid building blocks. In a biological sense such as the article mentions, that could be a concern if you want it to interact with (or avoid) other structures.
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In contrast, DNA can be made more or less fully synthetically, and the misfolding problem is a non-issue: it can be melted down and re-folded nearly infinitely.
See I was thinking the opposite, that the misfolding problem would be much bigger (though I'm not a biochemist and you are.) What's making sure the DNA folds back into the highly ordered secondary structure you're aiming for? DNA denatures and renatures mainly in the pairing, the secondary structures seem like they're much weaker and more promiscuous than protein structure. I would expect the box to fall apart much easier than a protein box, but again, that's not an expert opinion.
Re:DNA is economical (Score:4, Informative)
But here's my partially-educated guess as to why DNA folds "better": there are very few examples in which the very first folding steps for a protein is understood. As of a year or two ago, it was still up for debate which kind of interactions were the most important ones for forming the intial "seeds" that would lead to a fully-folded structure. Without being able to control the start of the folding, the search space for a random configuration to find the correct final fold is unimaginably huge.
In contrast, DNA folding follows more simple rules, and the initial folding steps can be easily controlled. So assuming you can initialize correct folding by properly engineered sequences, you just have to make sure it continues along the path. That makes it a directed, and much simpler, problem.
The stability of a DNA structure vs protein is going to depend highly on the specifics. But, you can design a double-stranded DNA segment that will separate into two individual strands at a very precise temperature, because you can specifically control the number of bonds (in a particular segment). It doesn't take a lot to get stability into the 80-100degC range, but that's just for two strands together, not for a full cage. I'm not sure at what point you would lose that level of stability.
For proteins, stability ranges across the whole spectrum. Some nanostructures fall apart if the salt concentration is just a little off, while others will be just fine near boiling: there are viruses that survive great in the geothermal features in Yellowstone.
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For proteins, stability ranges across the whole spectrum. Some nanostructures fall apart if the salt concentration is just a little off, while others will be just fine near boiling: there are viruses that survive great in the geothermal features in Yellowstone.
You've got to admire TAQ, even if it never amplifies what I want :-) But that illustrates my point, proteins are of course versatile in structures whereas DNA is not. It doesn't seem like there's any protein component to these cubes, and nothing I know of in DNA can crosslink strands like cystein bridges (besides holliday junctions, and they don't seem to be using them here.) It seems like you could design a strand of DNA that theoretically would form a box based on kinks in the helix, but I don't see ho
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IAAB (I am a biochemist)
The problem with protein folding, is that if it does not occur properly, unfolded proteins will stick together and form aggregates. These clumps of protein are stable, and so it is difficult to then seperate the proteins and let them fold properly.
In contrast, DNA is negatively charged, and does not clump together when it misfolds.
Comical name (Score:3, Insightful)
DNA Origami was given a comical name for a reason. This is just a curiosity. Maybe some day the technique will be used for something practical.. but more likely DNA synthesis technology will catch up and there will no longer be any need to "fold" an existing long single strand of DNA like a virus. It's actually more like "stapling" and that's how it is described in the literature, maybe they should have called it Milton Manipulation, but I guess few biologists would get the joke.
It's truly frightening that the vast majority of military spending that has gone into "nanotechnology" has been directed towards the Design-Ahead-ists, those who follow the wisdom of K. Eric Drexler. It's the new cold war, and its even colder than the last. Technology like DNA Origami and Ralph Merkle's continuing pursuit of STM/AFM techniques are literally the sparks that could ignite a Gray Goo Armageddon - or the abundant life.
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Hehe, no I wasn't suggesting it was, or that there was anything to fear from it. What I was suggesting is that DNA Origami and other techniques are the "primer" that will lead to real molecular manufacturing.. and once the first assembler is built there will be an explosion of activity due to the massive amounts of design-ahead research that has been done. Of course, that assumes that design-ahead has been done remotely accurately, which quite simply is most likely not the case :)
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Think of it as a modular structure: the individual components give you flexibility in tuning a structure to fulfill a variety of roles. The cage could be fine-tuned to assemble or disassemble at particular rates, or with variations in size. Each "staple" location is a site where you can add a modification to give new functionality. For example, the display of s
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Yeah, you're not getting it. Because we can't synthesize really long DNA strands with any sort of accuracy yet, DNA Origami was invented. You take some long single strand of DNA that you can get via other means and for which you know the sequence. You then synthesize short DNA fragments that will bind to the sequence as specific points. This causes the DNA to fold up into a mostly predictable shape. The problem is that the most ready supply of long single strands of DNA with known sequence is viruses.
Here's the paper (Score:3, Informative)
http://www.cs.duke.edu/~nikhil/.fnano09/u34bu3r/Self-AssembledDNANanostructures/PDF/For%20Review/E00-668912817.pdf [duke.edu]
Yeah, fuck you Nature.
Doh, just the abstract (Score:3, Funny)
Sigh.
Ok, really this time (Score:2)
http://heybryan.org/books/papers/Self-assembly%20of%20a%20nanoscale%20DNA%20box%20with%20a%20controllable%20lid.pdf [heybryan.org]
Thanks kanzure, you rock.
Blah blah blah. (Score:4, Funny)
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Who cares about cranes when someone could make a *flying dinosaur*?
Yes we can make a crane. (Score:2, Informative)
Drugs delivery !? (Score:1)
Very interesting and promising idea. Especially if design of this structures is possible "in silico". Since last few years , we can notice great progress in this area.
Irritating about speaking of this kind of research and achievement is that every time when they design nano-structure always first application of this have drug connection. Of course it looks good in newspapers, but unfortunately it obscures application that it can achieve in near future.
The reasons, why to applicate this in drugs delivery in