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"DNA Origami" Could Allow For Controlled Drug Delivery

timothy posted more than 5 years ago | from the biotech-ransom-possibilities dept.

Biotech 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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First post! (-1, Redundant)

Anonymous Coward | more than 5 years ago | (#27872781)

Yeah, first post! And I didn't even read the summary!

Anonymous Coward (0)

Anonymous Coward | more than 5 years ago | (#27872795)

Sure, if you want to give the immune system a heart-attack, grossly over complicate something that can be done better/faster/cheaper with dendrimers, and... what was the advantage of doing this again?

Re:Anonymous Coward (1)

interkin3tic (1469267) | more than 5 years ago | (#27873171)

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).

... so are you actually spreading FUD about technology which has no actual applications yet?

Re:Anonymous Coward (4, Informative)

The Mysterious Dr. X (1502541) | more than 5 years ago | (#27874161)

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.

Re:Anonymous Coward (1)

x2A (858210) | more than 5 years ago | (#27874523)

Yeah, ignorance is a go go! Wooo!!!

Expect DRM to come soon! (4, Funny)

freaker_TuC (7632) | more than 5 years ago | (#27872811)

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

Re:Expect DRM to come soon! (0)

Anonymous Coward | more than 5 years ago | (#27873003)

Imagine! A rootkit in the form of a virus...

Re:Expect DRM to come soon! (1)

jonaskoelker (922170) | more than 5 years ago | (#27881241)

Write your MEP's now!

Morphological Equivalent Privacy?

DNA is economical (5, Informative)

Vesvvi (1501135) | more than 5 years ago | (#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:DNA is economical (2, Interesting)

interkin3tic (1469267) | more than 5 years ago | (#27873207)

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 (4, Informative)

Vesvvi (1501135) | more than 5 years ago | (#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:DNA is economical (2, Insightful)

interkin3tic (1469267) | more than 5 years ago | (#27873755)

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 how it would be held together in real solutions.

I'm definitely going to have to read the real article when I have access.

Re:DNA is economical (3, Informative)

Anonymous Coward | more than 5 years ago | (#27873819)

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 (2, Insightful)

QuantumG (50515) | more than 5 years ago | (#27872891)

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.

Re:Comical name (0)

Anonymous Coward | more than 5 years ago | (#27873029)

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. Specific aptamers allow us to bind a variety of things to the origami including fluorescent dyes, proteins, and other nanoparticles.

Two important points:
1. Have no fear of the Grey Goo from this one. Particular DNA strands need to be added for the structures to grow. Self assembly yes but only with the added (and unnatural) building blocks.

2. Our work on DNA "origami" is funded by the NIH.
Sorry, no black helicopters. Please feel free to read to your heart's content and contribute if you are able:
http://www.biodesign.asu.edu/centers/smb/

Re:Comical name (1)

QuantumG (50515) | more than 5 years ago | (#27873079)

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 :)

Re:Comical name (1)

Vesvvi (1501135) | more than 5 years ago | (#27873087)

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 some short peptide sequences are sufficient to cause an organism to traffic the particle to one type of tissue exclusively. Modularity is a good thing.


As for practicality, perhaps you should consider that every cell in your body employs nanostructures as part of its general operation. As nanoscale engineers we're far behind the curve at even replicating what is currently in existence. There are thousands of problems out there just waiting to be solved as soon as we figure out how to do it.

Re:Comical name (1)

QuantumG (50515) | more than 5 years ago | (#27875131)

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. Making anything out of virus DNA kinda makes it a little dangerous for, oh, say, drug delivery in the human body.

hype much? (0)

Anonymous Coward | more than 5 years ago | (#27872913)

Lots of things *could* be used for drug delivery. How about demonstrating that things can be put into and taken out of these boxes before jumping to conclusions?

Protein capsules [ucla.edu] which can be opened and closed have been tested for more than 20 years. Loading those things with concentrated enough drugs to make them work has not been too easy.

DRM (0)

Anonymous Coward | more than 5 years ago | (#27872919)

All your DNA base (pairs) do belong to us

Here's the paper (2, Informative)

QuantumG (50515) | more than 5 years ago | (#27872975)

Doh, just the abstract (2, Funny)

QuantumG (50515) | more than 5 years ago | (#27872981)

Sigh.

Blah blah blah. (4, Funny)

Mr. Conrad (1461097) | more than 5 years ago | (#27873015)

Can they make a crane or not?

Re:Blah blah blah. (1)

Red Flayer (890720) | more than 5 years ago | (#27874757)

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*?

Yes we can make a crane. (2, Informative)

opticalbiophysics (1550145) | more than 5 years ago | (#27873073)

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. Specific aptamers allow us to bind a variety of things to the origami including fluorescent dyes, proteins, and other nanoparticles. Two important points: 1. Have no fear of the Grey Goo from this one. Particular DNA strands need to be added for the structures to grow. Self assembly yes but only with the added (and unnatural) building blocks. 2. Our work on DNA "origami" is funded by the NIH. Sorry, no black helicopters. Please feel free to read to your heart's content and contribute if you are able: http://www.biodesign.asu.edu/centers/smb/ [asu.edu]

Yum (0)

Anonymous Coward | more than 5 years ago | (#27873743)

Can I have a cube of DNA-25?

Controlled drugs (0)

Anonymous Coward | more than 5 years ago | (#27873749)

I wish someone would deliver some to me.

Drugs delivery !? (1)

angry_joker (1551039) | more than 5 years ago | (#27896363)

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 near future will be very hard, are :
+ putting drug inside box. It was shown that oligonucleotides can self-assembly but there were nothing about how to put drug molecule inside. Of course it is possible to build some empty boxes but it increases cost, and decreases efficiency of therapy. It can be easily solved if box could not be able to assembly in absence of (drug)molecule
+ The big problem is deliver box to specific place in organism. It's obvious that main target of this type of nano-structures are cells, because deliver to drug outside an cell (e.g: lymph) is not a problem. Cells are protected from free transport of compounds like proteins, nucleic acids etc. through lipid bilayer. If box wants to go through bilayer, its designer should "decorate" it using some other compounds. Then the risk of immune response increases.
+ some other problems mentioned by authors of this research.

But Andersen et.al. made big step forward.

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