"DNA Origami" Could Allow For Controlled Drug Delivery

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."

Comments

DNA is economical

[Vesvvi]

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

[Vesvvi]

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

[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.

Here's the paper

[QuantumG]

http://www.cs.duke.edu/~nikhil/.fnano09/u34bu3r/Self-AssembledDNANanostructures/PDF/For%20Review/E00-668912817.pdf

Yeah, fuck you Nature.

Yes we can make a crane.

[opticalbiophysics]

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:Anonymous Coward

[The Mysterious Dr. X]

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.