DNA Origami: Fold to the Future!

   

This post is about DNA. Every month there is a new publication heralding an innovative use of DNA. Go ahead, look it up on any science site: DNA machines are blasting us to the future. Scroll to the bottom for video links.

In March of this year, Caltech put on a conference and published an article: "Ten Years of DNA Origami." The fact that it has taken 10 years to gain real traction when it comes to potential medical applications for this technology seems to match the turn around time of other biotechnologies as well. According to this abstract over 20 therapies utilizing RNA interference are in clinical trials, some very close to being approved, and that won the Nobel in 2006. 10 years ago. These things take time. What will DNA origami do 10 years down the road? Whether it wins the Nobel or not doesn't matter, but will it be useful?

To say that scientists are now using DNA to build microscopic machines would be redundant, because DNA does that already.
 Indeed, one Professor Jungmann is already working on combining DNA origami with fluorescence to create even better “probes” into the microscopic plane. Seeing into such a small world is an important and competitive goal in science, one that has yielded some of the greatest discoveries of the modern age (think: microscope, x-ray crystallography, MRI). But I'm getting ahead of myself. Where did it all start?

James Watson, who helped discover DNA, said in his TED talk on discovering DNA "We can't patent this. No use for it!". In 1994, Paul Rothemund used DNA to make microscopic smiley faces that ended up on the cover of Nature. Rothemund sums it up better than I can: 

 "Think about DNA origami as a general-purpose pegboard for organizing nanometer-sized things," Rothemund says, "Each DNA origami has different attachment points, to which one can attach tiny gold balls, or fluorescent molecules, or electrically conductive carbon nanotubes. Biologists use DNA origami to position different protein enzymes next to each other, so that one enzyme can hand off its products to the next enzyme in a sort of nanoscale assembly line. Others are organizing electronic components in an attempt to make nanocircuits."

DNA origami, broadly speaking, is a process that takes advantage of the nucleic acid’s particular binding properties to form 2-dimensional and 3-dimensional shapes, microscopic machines, and materials. Some applications include targeted drug delivery, where a small DNA motor operates inside a host to deliver a payload at a specific location. Getting drugs to the right places, and in the right amounts, happens to be a prime functional problem in medicine. Cancer drugs are toxic, and many doctors dream of being able to limit such toxicity to certain areas like a metastasized tumor. A motorized drug-delivery system could save lives by keeping the toxic drugs in the cancerous locale. 

 Therapies utilizing DNA origami are still (probably) several years away, but just as RNA interference is finally beginning clinical trials 10 years after it was a Nobel prize-winning discovery, DNA origami will one day come into its own.

 

DNA origami began with static 2-d artwork, just like STM (scanning tunnel microscopy) started off with a 35 atom IBM logo in 1989. From Van Gogh to “spiders” made of DNA that walk down a track, this technology is an open field for creativity and innovation.

Initially, scientists tried to improve upon some biological “walkers” that are naturally used in our cells. A “spider” of DNA walking down a track with a drug payload has many legs to bind and detach from a track. These extra legs prevent the “spider” from falling off and delivering the drug to the wrong place, but they also slow the little machine down so much as to make them useless. A “walker” with less legs will throw itself off the track. Now, different designs have come out that completely abandon the designs already seen at work in cells, one of which is an RNA "wheel". DNA is not the only nucleic acid used in origami, because RNA has similar folding properties.

The spider and wheel are relatively small. Making a bigger machine out of DNA or RNA remains a particularly difficult challenge. Scientists have used lipids as a foundation to build DNA structures. They have created large “woven” sheets. As they try to create larger machines they become harder to control in a dynamic environment. 
  

The different experiments continue to grow in their ambition and intent, to the point that DNA origami may one day serve a whole cross-disciplinary range of purposes. In the meantime, it’s also a ton of fun to watch.

 Videos: 
Nature's "10 Years of DNA Origami"
The discoverer's TED talk
virus genome being folded into a sheet
                       
You can also make you're own design as a student and submit your structure to BIOMOD the molecular design competition.
  
--Written by Greg Brooks