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Biotech Medicine Science

"DNA Origami" Could Allow For Controlled Drug Delivery 29

Posted by timothy
from the biotech-ransom-possibilities dept.
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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"DNA Origami" Could Allow For Controlled Drug Delivery

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  • by freaker_TuC (7632) on Friday May 08, 2009 @01:05AM (#27872811) Homepage Journal

    DNA Rights Management... Write your MEP's now!

  • DNA is economical (Score:5, Informative)

    by Vesvvi (1501135) on Friday May 08, 2009 @01:17AM (#27872877)
    As a biochemist working in the area of structure/physics, of course I find this very interesting, and there's no shortage of things that could be said about this technique.

    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.
    • Re: (Score:3, Interesting)

      by interkin3tic (1469267)

      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)

        by Vesvvi (1501135) on Friday May 08, 2009 @02:52AM (#27873373)
        It would really take an expert in DNA folding (such as the authors of the paper) to give you a good answer to that.

        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.
        • Re: (Score:3, Insightful)

          by interkin3tic (1469267)

          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

        • Re: (Score:3, Informative)

          by Anonymous Coward

          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)

    by QuantumG (50515) * <> on Friday May 08, 2009 @01:19AM (#27872891) Homepage Journal

    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.

    • by Vesvvi (1501135)
      From a theoretical perspective, there are many reasons why a "stapled" DNA structure would be preferred to more convoluted one-piece structure.

      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
      • by QuantumG (50515) *

        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.

  • by Mr. Conrad (1461097) on Friday May 08, 2009 @01:44AM (#27873015)
    Can they make a crane or not?
    • McCrosky: Johnny! What can you make of this?
      Johnny: I can make a hat, a brooch, a pterodactyl...

      Who cares about cranes when someone could make a *flying dinosaur*?

  • The "DNA origami" are artificial strands of DNA that are held together at specific locations by staple strands. The strands are made to order from a commercial source. Software we wrote allows us to draw arbitrary (3D and 2D) shapes and have the purchase order automatically generated! It's really a wonderful nanotechnology, ideal for aqueous based situations where specific scale and proximity is required. Drug delivery is not the ideal application but for some reason this author seemed to think so. Specif
  • 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

"I'm not afraid of dying, I just don't want to be there when it happens." -- Woody Allen