Monthly Archives: June 2017

A Missouri farmer who spent nearly two decades in mental hospitals after entering a disputed plea in the 1997 sexual assault of a teenager has been cleared of the crime after genetic evidence was re-tested and excluded him as a suspect.

The top prosecutor in southwestern Missouri's Jasper County dropped the case against 58-year-old Mike Wilkerson last Friday, citing the recent DNA testing conducted on a cigarette butt and a condom found at the scene.

Its about darn time, Clint Wilkerson, who was 9 years old when his father was arrested, told The Joplin Globe.

The Globe reported that Wilkerson had to watch from the hospital as his family struggled to keep his586-acre cattle ranch.

The victim, who was 17 at the time, said she was sexually assaulted by a gunman who entered her home after pretending to be lost, and she identified Wilkerson as her attacker from a photo lineup.

Wilkerson pleaded not guilty by reason of insanity in 2000, and by Missouri law, he was ordered committed indefinitely to mental hospitals.

In such cases, defendants remain in the state Department of Mental Health's custody until they prove they no longer have a mental illness that could endanger themselves or others. Because Wilkerson's case involved a violent sex act, he faced the added burden of showing he understood the criminality of it essentially admitting it.

But Wilkerson has been unwavering in professing his innocence, his appeals attorney, Bill Fleischaker, said Wednesday.

"He stuck to his guns, and you've got to admire his courage," Fleischaker told The Associated Press. "There was an easy out, and he wasn't willing to take it."

A judge last year threw out that Wilkerson's plea, leading to Wilkerson being freed on bond in January pending a new trial and to prosecutors taking a fresh look at the evidence.

"I am dumbfounded they were able to get the DNA and accept that I was never at the crime scene," Wilkerson told the AP by phone, adding that his bipolar condition was stabilized with medication in 2003 and that he had been "just doing time" since then. "I was beginning to think I would never get out," he said.

Wilkerson lamented that he wasn't able to walk his daughter down the aisle and that he missed his son's wedding. Asked whether he might sue, though, he said he and his lawyers didn't know what they'd do.

Jasper County Prosecutor Theresa Kenney said prosecutors who initially handled the case failed to consider all of the evidence. At that time, only the condom found at the scene was tested for DNA, but that examination proved inconclusive with the technology available then.

Fleischaker said at the time Wilkerson pleaded not guilty by reason of insanity at his trial attorney's urging, he was financially troubled, bipolar and "very mentally ill."

"Mike didn't understand when he entered the not guilty by reason of mental disease or defect and the fact he had no other defense that that's the legal equivalent of saying you did it," Fleischaker said. "It's the legal equivalent of saying, 'I'm guilty but insane,' and that's the way it was treated.

"There were a lot of things done wrong that led to Mike being in the situation he was in."

Fleischaker said a DNA test he ordered on the cigarette butt in 2011 excluded Wilkerson as the source of the genetic material on it. He said Wilkerson's legal team didn't have access at the time to swabs of DNA taken from the condom.

Last year, a judge threw out Wilkerson's plea because state psychiatrists never concluded he was insane at the time of the crime. Wilkerson later pleaded not guilty, prompting prosecutors to resubmit the evidence for DNA testing, which ultimately cleared him.

"It's been a long road," Fleischaker said. "The key to this thing is we felt all along the DNA would exonerate him. The problem is there were a lot of procedural hurdles we had to get over."

Wilkerson is reportedly making plans for a steak dinner with his family.

I lost 20 years. I lost time with my kids. Thats what I regret, he said.

The Associated Press contributed to this report

Read this article:
Missouri farmer cleared in 1997 sex case by DNA evidence - Fox News

E

ven if you didnt take art history classes in school, you probably know Salvador Dals work. One of the surrealists most famous paintings, The Persistence of Memory, is the one with the melting clocks.

But memory is not the only thing that persists a woman who has claimed to be Dals daughter for over a decade has not given up. To support her contention, Pilar Abel has had two previous paternity tests performed one with inconclusive results, another that allegedly never sent her results. Now a Spanish court has granted her request to have Dals body exhumed from a crypt in Catalonia so a third test can be conducted.

But Dal has been dead for nearly 30 years. Can a sample of his DNA still give Abel a definitive answer?

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Yes and no, saidHendrik Poinar, principal investigator at the McMaster Ancient DNA Center in Ontario, Canada. The success of the test will depend on a lot of factors including, possibly, which kind of analysis is done.

Poinar isnt involved in the case, but he is trying to solve a mystery about another famous 20th-century artist. Hes analyzing the remains of poet and Nobel laureate Pablo Neruda to determine if a bacteria was involved in his death in 1973.

Genetic fossil-hunters dig through HIVs long history for clues to new treatments

The researchers working with Dals DNA will need to consider two main issues: contamination during the exhumation and working with degraded DNA afterward, Poinar said.

Though Dal died in 1989 certainly not ancient history your DNA degrades the minute you die, Poinar said. He and his students will often define ancient DNA as anything thats buried in the ground.

A sample will likely come from one of three places: hair, a molar tooth, or a small but very compact bone in the skull near the inner ear. Hair is pretty resistant to contamination, Poinar said, and the bone called thepetrous bone has the most DNA per gram of any part of the skeleton.

A standard forensics lab might take these samples, extract DNA, and look at a set of more than a dozen microsatellites, Poinar said. Each microsatellite can range from 100 to 400 DNA base pairs long and can vary in only so many ways in which DNA bases repeat and how many times they repeat. (These repeating sequences are called short tandem repeats, or STRs; looking for them is called STR analysis.)

For comparison, the human genome is about 3 billion base pairs long.The possible patterns are numerous enough that determining if two samples come from the same person or if the donor of one sample is likely related to the other is very possible.

However, Dals DNA may be in shorter fragments which may mean this DNA profiling technique will be less reliable. In Poinars experience, the average length of a DNA fragment from skeletal remains is about 70 to 80 base pairs so the average fragment would likely have only part of a satellite region. If many of these microsatellites are compromised, then the analysis loses a lot of statistical power.

Instead, he and other ancient DNA experts working in more specialized labs prefer sequencing full genomes and comparing a collection of single nucleotide polymorphisms, or SNPs (pronounced snips), which are variations in just one base pair.

The burial environment what kind of casket Dal was buried in could have an effect, for example, or any kind of treatment his body received before burial can have a impact on the condition of DNA. Only the people on the ground during the exhumation and those who actually sequence the sample will know what state the DNA is in, noted Reena Roy, an associate professor in the forensic science program at Pennsylvania State University. Without being there or using other techniques to determine how degraded the DNA actually is, she said, one can only speculate.

Roy suspects Dals DNA could be in decent shape its only 30 years old, she said. Shed still use STR analysis first, but if that didnt seem to work, shed consider using miniSTR testing, which uses the same principles but focuses on smaller DNA segments.

Bottom line: Though the circumstances around the particular paternity case may be a bit surreal, the techniques themselves are not; STR analysis is usually done in paternity cases, Roy said.

This is so routine these days.

Kate Sheridan can be reached at kate.sheridan@statnews.com Follow Kate on Twitter @sheridan_kate

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Dal's being dug up for a paternity test. But is his DNA intact? - STAT

We are a society obsessed with information. Were constantly connected, click-click-clicking to access a steady stream of news, data, and social-media updates. Curiosity is a powerful motivator, but theres one area in which our thirst for knowledge has been inconsistent: genetic testing.

DNA tests have become du jour in the past decade. Technological advances and access to genomic testing translates into the ability to see whats beneath the hood of our chromosomal cars. Weve become obsessed with ancestry tests like 23andMe and finding out our babies sexes before theyre born, but we often shy away when it comes to more serious curiosities. Even though you can now easily find out if you carry the genetic mutations or changes for recessive diseases like spinal muscular atrophy, we often dont test for these genetic glitches because we just dont want to know. But its important that we find out.

Theres no doubt that genetics is complicated, and maybe its that lack of certainty that deters some people from diving into their DNA. Genetic disease can be confusing, with some mutations definitely resulting in disease and others leading only to increased risk. Some genetic diseases require that both parents have a mutation in order to stand a chance of having an affected child; others can be triggered by just one parent possessing a mutation. Its a bit of a crapshoot.

With so many diseases and conditions transmitted in different ways and identifiable at different stages of pregnancy, its no wonder that some women choose to forego prenatal testing at all; adopting a head-in-the-sand approach can be easier to cope with than grappling with the uncertainties raised by a DNA test.

But when it comes to prenatal testing, information is always a good thing. Knowing ahead of time about a condition can allow parents to set up a support network of family and friends and connect with other parents who have a child with a similar diagnosis. They can learn more about the condition with which their fetus has been diagnosed, seek out medical specialists ahead of time, and choose to deliver at a hospital that has the appropriate level of care for a baby with special needs.

Being surprised by an unexpected diagnosis on the day of delivery turns what should have been a joyous day into a day marked by confusion and fear.I interviewed scores of mothers for my book, The Gene Machine: How Genetic Technologies Are Changing the Way We Have KidsAnd the Kids We Have. In speaking with numerous women who didnt know while pregnant that they would give birth to children with special needs, Ive heard a common theme. Moms say that being surprised by an unexpected diagnosis on the day of delivery turned what should have been a joyous daythe birth of their childinto a day marked by confusion and fear. They wish they would have been aware of their childs diagnosis so that they could have come to terms with it before giving birth. That awareness could have allowed them to educate themselves and to prepare mentally and emotionally. It could have given them a jumpstart on processing and resolving the inevitable feelings of loss that come with learning that the baby youd hoped for is not the baby you have.

Pregnancy is not a perfect science; things can and do go awry. Worldwide, an astounding 8 million babies6% of birthsare born with a birth defect, many of which can be traced to genetics.

But even when the baby you give birth to may not be the perfect baby you expected, arming yourself with information ahead of time can make a big difference in how you process the experience of having a child with special needs. In 1987, Sesame Street writer Emily Perl Kingsley wrote about reconciling reality with expectations after the birth of her son, Jason, who was born in 1974 with Down syndrome.

When youre going to have a baby, its like planning a fabulous vacation trip to Italy. You buy a bunch of guidebooks and make wonderful plans. After months of eager anticipation, the day finally arrives. You pack your bags and off you go. Several hours later, the plane lands. The stewardess comes in and says, Welcome to Holland. Holland?!? you say. What do you mean Holland? I signed up for Italy! Im supposed to be in Italy. All my life Ive dreamed of going to Italy.

Some women decline genetic testing because they say that even if they receive a concerning diagnosis, they wouldnt alter the course of their pregnancy anyway. But thats rarely the case. As one genetic counselor told me, shes never had a couple do absolutely nothing upon learning that their fetus has a health issue. When people say they wouldnt do anything differently, she said, thats simply not true. Do anything differently is often code for abortion, yet ending a pregnancy is just one option upon receiving concerning genetic-test results. Many parents decide to continue an affected pregnancy.

Other women turn down the offer of genetic testing either because theyre overwhelmed by its complexity or because they mistakenly think theyre in the clear because they have no family history of genetic conditions. But family history, while useful, is a poor predictor of potential problems.

Consider autosomal recessive diseases such as cystic fibrosis, which affects one in 2,500 white babies. (Its less common in African American and Asian populations). If both parents carry the same genetic mutation, their children have only a 25% chance of developing the disease. Compare this with autosomal dominant mutations such as BRCA, often called the breast cancer gene. If either parent has a BRCA mutation, theres a 50% chance of passing that same genetic change to a child. Then there are conditions such as Down syndrome, which arent typically inherited and instead occur randomly around the time of conception.

Just because no one in your family suffers from a recessive disease doesnt mean youre not a carrier of it. Think back to those autosomal recessive diseases such as cystic fibrosis that occur only if both parents carry a mutation. Each pregnancy conceived by these carrier couples only has a 25% chance of developing the diseasethat means theres a 75% chance that any child will be disease-free. A mutation for one of these diseases could be unknowingly passed down for generations before two partners with the same mutation find one another and make a baby that has the unfortunate luck to inherit both problematic mutations.

We are no longer living in an era in which women have no choice but to remain in the dark about the health of their unborn children. All parents stand to benefit from knowing about potential problems ahead of time, which allows them to be proactive and take charge. Genetic testing before and during pregnancy can empower parents to make the decisions that are right for them, whether the itinerary of parenting leads them to Italy, Holland, or somewhere in between.

Learn how to write for Quartz Ideas. We welcome your comments at ideas@qz.com.

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The real reason why all women should get their DNA tested - Quartz

June 28, 2017 11:35 PM

NEW YORK (CBSNewYork) At-home DNA tests have exploded in popularity, but could they reveal more about your family than you ever imaged or even wanted to know?

DNA has changed, absolutely. There can be no more secrets, Zara Phillips tells CBS2s Dick Brennan.

Nobody knows this better than Phillips, who took a DNA test two years ago. A year later, she was contacted by a sister that she never knew she had.

I was hyperventilating, she says.

Genealogy is said to be the second most popular hobby in the United States, and its been spurred on by a number of new at-home DNA kits. But for some, the popular pastime has a completely different purpose than exploring their family tree.

I hold a lot of hope that I will be able to find my biological father through this, April Dinwoodie says.

For those like Dinwoodie, who was given up for adoption in the 1970s, it may be the only way to help find her family.

In many states, almost half dont allow adoptive people access to their legal birth certificates, she says.

That includes New York.

Thats a very old and outdated policy, says Joyce Bahr, an adoptee advocate.

She says she was forced to give up her son in the 1960s.

What wed like to see end is the secrecy and lies in adoption, Bahr says.

But some lawmakers disagree.

Ironically, DNA kits are starting to rip the lid off these records.

Anonymity today is a thing of the past with these tools, Dinwoodie says.

Shes now with the Donaldson Adoption Institute and says not only can you compare you genetic makeup to that of millions of other people in the databases, you can also send a message to anyone who is match. But it may not always be met with an open mind or open arms.

Rejection it can be major, it can be extremely painful for some people, Bahr says.

In Phillips case, the DNA test was a last-ditch effort to locate her biological father, who she believed was in Europe. It came as a shock, to not only learn about her sister, but that her dad was actually living just a few miles from her in New Jersey.

I never even dreamed that this was going to be possible for me, she says.

Phillips is now writing a book about her experience that will be published next year.

Because the experience can often be very emotional and difficult to navigate, experts recommend working with a counselor or middleman who can help facilitate a reunion.

Adoption agencies can provide counseling for families. For more information, contact The Donaldson Adoption Institute.

Original post:
Seen At 11: DNA Tests Kits Help Adoptees Track Down Biological Family Members - CBS New York

Some animals are just impossibly weird (see: the platypus). But members of the genus Macrauchenia are, by nature of being very much extinct, a tad more mysterious than even our most perplexing modern creatures.

When Charles Darwin first dug up pieces of these animals in 1834, he and paleontologist Richard Owen were seriously stumped. The animal's body shape seemed fairly camel- or llama-esque (indeed, the name of the genus translates to "long llama") but it had triple-hooved feet that resembled those of a rhinoceros. Most perplexing was its nose: unlike the majority of mammals, the nostril holes on its skull were high atop the head, between the eye sockets. Scientists now believe this is the sign of some kind of trunk, but it was once suggested that they actually used them as some kind of snorkel.

The South American genus, which seems to have died out for good around 10,000 years ago and has no living descendants, has been basically without a family since its discovery. In 2015, a study of the proteins inside the ancient bones suggested a close kinship to perissodactyla, an order of "odd-toed ungulates" that includes tapirs, rhinoceroses, horses and their ilk. According to that analysis, Macrauchenia had branched off from the lineage of any surviving ungulates about 60 million years or so. But while the study of proteins allowed scientists to infer what the animals' DNA might have looked likeproteins are, after all, created under the instruction of the genes carried by our DNApaleontologists were unable to get at the DNA itself. Until now.

In a study published Tuesday in Nature Communications, an international team of researchers announced success in tracing out the genetic history of the unusual ungulates. And it took some creative thinking. Ancient DNA is difficult to study because DNA degrades quickly (especially in warm, wet environments like South America), so scientists have to piece together a fossil's genetic code using whatever clues are still around. Even mitochondrial DNA, which is passed down directly from mother to child, stored in the power house of the cell, and generally more resilient than the DNA kept in the nucleus, is quickly degraded by the ravages of time.

We had a difficult problem to solve here: Macrauchenia doesnt have any really close living relatives, lead author Mick Westbury from the University of Potsdam said in a statement. Because ancient DNA is so degraded and full of unwanted environmental DNA, we rely on being able to use the genomes of close relatives as a kind of scaffold to reconstruct fossil sequences. For this study, we devised a new approach involving iterative mapping that relies on using very strict parameters and the mitochondrial genomes of a number of living species as multiple reference points to more reliably predict the fossils most likely genetic sequences.

In other words, they analyzed the genome by comparing it to a bunch of known genomes over and over, guiding the DNA fragments they did have into their most likely complete form. They were able to recover 80 percent of the mitochondrial DNA from one of the fossils they studied, which allowed them to confidently map its relationship to living animals. Lo and behold, they also concluded that Macrauchenia was most closely related to perissodactyla, though it wasn't actually in the same lineage as any of the creatures alive in that group today. And their estimate of when the extinct weirdos diverges from the modern weirdosabout 66 million years agolines up with the findings of the protein study as well. The techniques used in both of these studies are pretty new, so the fact that they came to the same conclusion does a lot to support their findings.

The study authors note that their estimation puts the divergence of Macrauchenia right smack dab in the middle of the mass extinction event that killed off most dinosaursa period when mammals were suddenly able to thrive and evolve to fill newly empty ecological nichesbut they don't necessarily think that these trunked animals have dinosaur death to thank for their existence.

While the coincidence with the extinction of nonavian dinosaurs was not lost on us, molecular clock dating is more like a sundial than a digital watchits just not that precise, study author Ross MacPhee, a mammalogist and curator at the American Museum of Natural History, said in a statement. While fossils certainly support the idea that the modern orders of placental mammals really began to diversify around this time, molecular evidence suggests that their broader relationships go back into the late Mesozoic, before the big die-off. The deep lineages that make up Panperissodactyla are certainly consistent with this idea, but we need to find the fossils to document it.

But the team has even stranger beasts on their to-do list (if you ask Darwin, anyway). They hope to use the same technique to confirm the history of Toxodon, another South American genus that Darwin called the "strangest animal ever discovered." Scientists think it looked something like a furry hippo with a rhino-like head.

Go here to read the rest:
DNA may finally find a family for strange creatures that stumped Darwin - Popular Science

P. Rothemund et al./Caltech

Van Gogh's The Starry Night recreated using DNA.

Vincent van Gogh's The Starry Night is a classic of post-Impressionist art. Its whimsical whorls have entranced art lovers since the Dutch artist painted it in 1889. In 2016, Paul Rothemund, a bioengineer at the California Institute of Technology in Pasadena, recreated the work. But instead of oils, Rothemund drew his copy in DNA.

Drawn on a silicon chip, Rothemund's creation demonstrates the growing power of a once-obscure branch of materials science: DNA nanotechnology. The field emerged in the 1990s when scientists began to dream up nanoscale machines. Today, more than 300 research groups are trying to harness the base-pairing properties of DNA, with the goal of manipulating the molecule as if it were a building material, rather than a carrier of genetic information.

Once we realized you can use the information in DNA to organize stuff, it started a cascade of activity.

Once we started to realize that you can use the information in DNA to organize stuff, it started a cascade of activity, says Ned Seeman, a synthetic chemist at New York University who is widely acknowledged to be the founder of DNA nanotechnology.

DNA's dimensions make it ideal for building nanostructures: the double helix is a flexible, configurable rod, 2 nanometres wide, with a twist that repeats every 3.43.6 nm. Researchers have exploited the well-characterized structure, and the ease of synthesizing custom DNA, to build ever-more-elaborate designs for applications from drug delivery and diagnostics to nanofabrication. But challenges remain, and nanotechnologists are rethinking the fundamentals of building with DNA.

The collection of shapes assembled from DNA ranges from 2D smiley-faced emojis to 3D geometrical objects and blocks of alphabetic characters. But the underlying technology is based on one simple rule: base-pair complementarity. Driven by hydrogen bonds that pair the bases adenine and thymine, and cytosine and guanine, complementary DNA strands will spontaneously form a double helix. In nature, the two strands are usually fully complementary. If strands are only partially complementary, however, both can accept multiple DNA partners. This concept, says Rothemund, is the foundation of DNA nanotechnology.

During cell division, DNA forms a four-armed intermediate structure known as a Holliday junction. The structure is unstable and disintegrates quickly into two double helices. In the early 1980s, Seeman managed to stabilize it1 by pairing each strand's sequence with another at the junction. He went on to produce a junction with six strands, forming the first branched DNA structure in 3D. A series of increasingly complex designs followed: a stick cube in 1991, branched DNA crystals in 1998 and DNA tubes in 2005.

In 2004, William Shih, a biochemist now at the Wyss Institute for Biologically Inspired Engineering at Harvard University in Boston, Massachusetts, took a different approach. He formed a 22-nm-wide octahedron from just a single strand of DNA2. The 1,669-base DNA strand was held in shape using five 40-base strands.

Building on this idea, two years later, Rothemund used hundreds of 26- to 32-base segments of DNA that he called staples to guide the folding of a 7-kilobase 'scaffold' strand into a variety of 2D shapes roughly 100 nm in diameter3. This was a landmark achievement, says DNA scientist Peng Yin, also at the Wyss Institute, because it greatly increased the complexity and size of DNA nanostructures.

Rothemund built his structures using the single-stranded DNA of a virus as a scaffold the DNA required was too long for conventional oligonucleotide synthesis. He worked out how the DNA could be folded and where the 200 or so staples would need to attach to form shapes such as squares, triangles, stars and smiley faces. By mixing the DNA with a 100 times more staples than were needed, heating to 95 C and cooling to room temperature over 2 hours, the shapes formed spontaneously on the basis of the instructions programmed into their sequences.

DNA 'origami' has come a long way since then. Initially, says Shawn Douglas, a biophysicist at the University of California, San Francisco, it could take an entire month to work out where the folds and staples go for just one design. It was easy to make mistakes, he says, and also hard to make modifications. This challenge inspired Douglas to develop software to accelerate origami design (see 'DNA origami'). The first working version of caDNAno was built in 2009, while Douglas was completing his PhD in Shih's group at Harvard. The software cut origami design to one day4. In the next 3 months, we made 30 shapes, says Douglas, including rectangular blocks, crosses and genie bottles.

Folding DNA typically begins with choosing a scaffold. Single-stranded sequences of up to 200 bases can be synthesized relatively easily, but beyond that, it is simpler to use viral DNA.

Once a shape has been chosen, the software tools caDNAno or DAEDALUS can be used to help design the structure. caDNAno can map a preselected sequence in the desired shape, identify crossover points and generate the short strands of DNA or 'staples' required to fold it. With DAEDALUS, only the desired geometry is needed; the software generates the scaffold and staple sequences. The blueprints can be checked for accuracy using the tool CanDo, which predicts the 3D structure.

The strands are then mixed together in the right ratios (with an excess of staples), heated and cooled. Well-formed DNA nanostructures are seen on gel electrophoresis as sharp bands that are distinct from the starting material. They can be further characterized using electron microscopy or atomic force microscopy. If no band is present, the DNA either failed to fold or the yield was low. This could be due to a design mistake, especially at crossover points. If the design is correct, the folding conditions may need to be optimized by tuning parameters such as the buffer, temperature and reaction time.

For researchers who don't want to create their own DNA nanomaterials, Tilibit Nanosystems in Garching, Germany, supplies made-to-order structures and prefabricated structures and kits.

A couple of years later, another team, led by biophysicist Mark Bathe at the Massachusetts Institute of Technology in Cambridge, developed an ancillary tool called CanDo5 to check the DNA origami blueprint from caDNAno. It will tell you what it thinks the structure looks like in 3D, says Bathe. Bathe's group has since developed a tool called DAEDALUS that tells users all the sequences, including the scaffold, they need just by entering a desired geometry6.

Another way to build with DNA is using DNA bricks. In 2012, while a postdoctoral fellow in Shih's lab, Yonggang Ke, a biochemist now at Georgia Institute of Technology and Emory University in Atlanta, developed a technique in which every brick in a DNA nanostructure has a unique sequence of 32 or 42 bases. A quarter of each sequence is complementary to another quarter on a different brick. By connecting and extending the bricks, researchers can assemble a canvas like building a brick wall. Each brick can bind to two at the top and two at the bottom, Yin explains.

For a flat, 2D canvas, the bricks contain 10.5 bases per quarter, which allows them to connect to each other in a single plane; any 2D pattern can be prepared by simply picking the correct bricks. To add a third dimension, Ke shortened the bricks to eight bases per quarter, which forced them to connect perpendicularly. The researchers produced 102 distinct structures, including hearts, spheres and the Roman alphabet7. In that first paper, we produced more 3D structures than the whole field combined, says Yin.

One use for these novel DNA shapes is to carry materials such as drug molecules, metal nanoparticles and proteins. Positioning these useful materials on the DNA is generally easiest before it is coaxed into a structure. The cargo is typically carried on the staple strands, and because each structure can include some 200 staples, says Rothemund, they offer plenty of opportunities to precisely place the molecular cargo.

DNA molecules are charged, which means that nanostructures can be arranged electrostatically by etching a pattern of negatively charged binding sites on a flat surface using an electron beam. You can get them exactly where you want, oriented how you want, says Rothemund. This is just what his team demonstrated when it recreated The Starry Night from a dense array of photonic crystal cavities micrometre-sized devices in which light can resonate that contained meticulously placed DNA nanostructures carrying dyes8.

Another idea is to cast nanoparticles using DNA nanostructures as the mould. This requires fairly large and stiff DNA nanostructures with internal cavities. In collaboration with Bathe's team, Yin's group built such structures using DNA bricks. The teams then introduced silver nanoparticle seeds into the cavities, and allowed them to develop in the presence of soluble silver, like rock sugar growing in supersaturated solution. The seeds developed to fill the cavities, producing cubic, spherical, triangular and Y-shaped nanoparticles9.

P. Rothemund/Caltech

Smiley-faced emojis are one of the many shapes assembled from DNA.

Chad Mirkin, a chemist at Northwestern University in Evanston, Illinois, is pursuing yet another nano-strategy, which he calls programmable atom equivalents. These nanoparticle cores can range from metals and polymers to proteins. Hundreds of partially double-stranded DNA molecules are attached to the core's surface to form a dense DNA shell. The single-stranded free ends are complementary to the free ends of other 'atom equivalents'. When those structures are mixed together, they link up and extend into a crystal lattice that positions the desired atoms precisely in space. This is an incredibly reliable method, says Mirkin.

Remarkably, the crystal's structure and properties can be controlled by varying the sizes and shapes of the nanoparticle cores, as well as the length of the DNA strands no small achievement, given that crystallization processes are notoriously tricky. We are trading ill-defined materials chemistry for well-defined and programmable DNA interactions to form high-quality crystals, and we can guide it down a path, says Mirkin, whose research group has churned out more than 40 crystal symmetries, 6 of which have never been observed in nature.

One popular adornment to nanostructured DNA is light-emitting materials called fluorophores. GATTAquant DNA Nanotechnologies in Braunschweig, Germany, for instance, makes nanorulers from DNA origami structures and fluorescent molecules to validate super-resolution microscopes. Super-resolution microscopy allows researchers to take images beyond the resolution limit set by the diffraction of light, but there is no standard to measure the resolution of the system, says Max Scheible, head of research and development at GATTAquant. DNA nanotechnology really enabled this.

GATTAquant attaches fluorescent molecules at precise distances on an origami structure and mounts them on glass slides. These nanoscale rulers allow researchers to verify the resolution of sub-diffraction-limit microscopes.

The co-founders of Ultivue, a start-up company in Cambridge, Massachusetts, are hoping to use nanostructures to make an impact in cancer research. In cancer tissues, biomarkers such as the proteins BRCA1 and HER2 can herald the onset or progression of disease, and can potentially aid diagnosis, prognosis and treatment. Until now, most biomarkers have been studied in isolation. What's missing is a fingerprint of biomarkers as they are seen in cancerous tissue, says Mael Manesse, lead researcher at Ultivue.

At Ultivue's headquarters, Manesse demonstrates the company's technology. Lit on the computer monitor are cells from a thin slice of lung tissue that Manesse has positioned under a microscope. When he switches the microscope's light to red, the cells disappear. In their place is a smattering of bright spots, indicating CD3 a biomarker for immune cells called T cells. These proteins are marked with Ultivue's DNA-based imaging probe: a short 'docking' strand attached through an antibody, and its complementary 'imaging' strand carrying a fluorescent dye. Each biomarker of interest has its own docking strand; the complementary imaging strands can be added, imaged and removed one at a time. The images are then superimposed to obtain a composite picture of the tissue. This allows almost unlimited numbers of biomarkers to be studied, but the tissue sample remains preserved, says Manesse.

DNA nanostructures can also be used to build sensors, drugs and vaccines for therapeutic or diagnostic applications. For example, researchers have made a synthetic vaccine by anchoring the antigen streptavidin and oligonucleotides with an immune-response-boosting, repeating cytosineguanine motif on tetrahedral DNA nanostructures10. In mouse studies, the vaccine produced higher levels of antibodies against streptavidin than a mixture of just streptavidin and oligonucleotides.

Eventually, Shih hopes to make drug nanofactories: DNA origami nanocapsules that can produce drugs on demand inside the body using building blocks from the cell. It is very exploratory at this point, he says. In theory, the nanocapsules would hold RNA polymerase an enzyme that makes RNA and DNA templates. Once triggered, it would begin manufacturing and releasing its payload, like a virus using cellular materials to replicate itself.

Although well into its third decade, DNA nanotechnology still faces a number of challenges. One key obstacle, says biophysicist Hendrik Dietz at the Technical University of Munich, Germany, is production yield: researchers have yet to break into gram-scale synthesis. DNA origami can make a very big difference in health, Dietz says. But the problem is we can't even make quantities that are big enough to use.

Another hurdle is the limited variety of materials that can be attached to DNA. Researchers are working to expand origami designs to use materials other than DNA. Earlier this year, for example, Dietz reported the preparation of DNA structures that fold using protein staples11, and Douglas is updating caDNAno to include RNA and protein building blocks.

Perhaps the biggest limitation is the lack of control over the self-assembly process. As structures get larger, the chances of misfolding increase. We need new strategies to suppress self-assembly errors, says Shih.

One possibility, Rothemund suggests, would be to move away from the standard in vitro method of mixing, heating and cooling, and allow cells to build the structures instead. Last year, bioengineer Christopher Voigt at the Massachusetts Institute of Technology engineered the bacterium Escherichia coli to produce a simple, branched, four-part junction from single-stranded DNA12. But for more-complex origami nanostructures, Rothemund says, a shift to RNA may be necessary. Unlike DNA, single-stranded RNA can hold its shape without staples. Building with RNA is largely uncharted territory, but Rothemund is excited to explore it. It is like building with wood, but now you can't use nails or notches or glue, he says. We still need to learn a lot of things.

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The architecture of structured DNA - Nature.com