ScienceDaily (Sep. 13, 2012) Scientists at Karolinska Institutet in Sweden describe in a new study how so-called DNA origami can enhance the effect of certain cytostatics used in the treatment of cancer. With the aid of modern nanotechnology, scientists can target drugs direct to the tumour while leaving surrounding healthy tissue untouched.

The drug doxorubicin has long been used as a cytostatic (toxin) for cancer treatment but can cause serious adverse reactions such as myocardial disease and severe nausea. Because of this, scientists have been trying to find a means of delivering the drug to the morbid tumour cells without affecting healthy cells. A possible solution that many are pinning their hopes on is to use different types of nanoparticles as 'projectiles' primed with the active substance.

In the present study, which is published in the scientific journal ACS Nano, scientists at Karolinska Institutet show how DNA origami can be used as such a projectile (or carrier) of doxorubicin. DNA origami is a new technique for building nanostrucutres from DNA, the hereditary material found in the cell nucleus. Using this technique, researchers can produce highly complex nanostrucutres with surfaces to which complex patterns of proteins and many other molecules can easily be attached.

What the researchers did on this occasion was to package the doxorubicin in a DNA origami configuration designed in such a way that relaxed the degree of twist of the DNA double helix. This allowed the drug to be released more slowly and operate more effectively on the cancer cells at lower concentrations than is otherwise possible.

"When the DNA has a lower degree of twist, there's more room for the doxorubicin to become attached, which leads to its slower release," says group leader Dr Bjrn Hgberg. "Another advantage to using DNA origami is that we will quickly be able to develop the targeted protein system. This will enable us to deliver drugs in a way that is even more sparing of healthy cells."

The study has been financed with grants from several bodies, including the Swedish research Council, Vinnova (the Swedish governmental agency for innovation systems), the Royal Swedish Academy of Sciences, the Falk Foundation, the Jeansson foundations, Carl Bennet AB and the Axel and Eva Wallstrm Foundation.

Publication: 'A DNA Origami Delivery System for Cancer Therapy with Tunable Release Properties', Yong-Xing Zhao, Alan Shaw, Xianghui Zeng, Erik Benson, Andreas M. Nystrm & Bjrn Hgberg, ACS Nano, online first 5 September 2012.

Share this story on Facebook, Twitter, and Google:

Other social bookmarking and sharing tools:

Story Source:

Continue reading here:
Under-twisted DNA origami delivers cancer drugs to tumors

Sequenom has appointed Myla Lai-Goldman to its board of directors and to the board's science committee. Lai-Goldman is a managing partner at Personalized Science and CEO of GeneCentric Diagnostics. Previously, she served as executive vice president, chief medical officer, and chief scientific officer at Laboratory Corporation of America.

Aushon BioSystems has appointed Martin Verhoef to be company CEO and to serve on its board of directors. Verhoef takes over the position from company Founder Peter Honkanen, who will assume the post of COO and will continue as a board director.

Verhoef has spent 25 years in the life science research tools and molecular diagnostics business. He formerly was CEO at MiraDx and PrimeraDx, he led Ciphergen's Biosystems Division, and he held senior management jobs at Agilent in Germany and in the US.

The New York Genome Center has appointed Dirk Evers and Kevin Shianna to its leadership team. Evers, who will serve as senior vice president of bioinformatics, joins NYGC from Illumina, where he led the company's computational biology efforts in the UK. Previously, he served as managing director of the International Graduate School in Bioinformatics and Genome Research at the Center for Biotechnology at Bielefeld University. Shianna will serve as senior vice president of sequencing operations at the NYGC. He joins from Duke University, where he was an assistant professor in the School of Medicine, director of operations for the Center for Human Genome Variation, and founding director for the Genomic Analysis Facility.

Read more here:
LBNL Seeks Licensees for Highly Specific and Sensitive DNA Extraction Method

Among the many mysteries of human biology is why complex diseases such as diabetes, high blood pressure and psychiatric disorders are so difficult to predict and, often, to treat. An equally perplexing puzzle is why one individual gets a disease such as cancer or depression, while an identical twin remains perfectly healthy.

Now scientists have discovered a vital clue to unraveling these riddles.

The human genome is packed with at least 4 million gene switches that reside in bits of DNA that once were dismissed as junk but that turn out to play critical roles in controlling how cells, organs and other tissues behave.

The discovery, considered a major medical and scientific breakthrough, has enormous implications for human health because many complex diseases appear to be caused by tiny changes in hundreds of gene switches.

The findings are the fruit of an immense federal project, involving 440 scientists from 32 labs around the world.

As they delved into the junk parts of the DNA that are not actual genes containing instructions for proteins they discovered it's not junk at all. At least 80 percent of it is active and needed.

The result is an annotated road map of much of this DNA, noting what it's doing and how.

It includes the system of switches that, acting like dimmer switches for lights, control which genes are used in a cell and when they are used, and determine, for instance, whether a cell becomes a liver cell or a neuron.

The findings have immediate applications for understanding how alterations in the nongene parts of DNA contribute to human diseases, which may in turn lead to new drugs.

They also can help explain how the environment can affect disease risk.

Read this article:
DNA ‘junk' contains a treasure of information about disease

ENCODE (Image: Ed Yong)

The recent dustup over the ENCODE project and its confusing finding that 80% of DNA is functional surprises me greatly. What surprises me especially is that people are surprised by junk DNA. Unfortunately this time the scientists are also culpable since, while the publicity surrounding ENCODE has been a media disaster, the 80% claim originated in the scientific papers themselves. There is no doubt that the project itself which represents a triumph of teamwork, dogged pursuit, technological mastery and first-rate science has produced enormously useful data, and there is no doubt it will continue to do so. What is in doubt is how long it will take for the public damage to be repaired.

Theres a lot written about the various misleading statements about the project made by both scientists and journalists and I cannot add much to it. All I can do is to point to some excellent articles:Larry Moran has waged a longstanding effort to spread the true wisdom about junk DNA for years on his blog. Ed Yong exhaustively summarizes a long list of opinions, links and analysis. T. Ryan Gregory has some great posts dispelling the myth of the myth of junk DNA. And John Timmer has the best popular account of the matter. The biggest mistake on the part of the scientists was to define functional so loosely that it could mean pretty much all of DNA. The second big mistake was not in clarifying what functional means to the public.

But what I found astonishing was why its so hard for people to accept that much of DNA must indeed be junk. Even to someone like me who is not an expert, the existence of junk DNA appeared perfectly normal. I think that junk DNA shouldnt shock us at all if we accept the standard evolutionary picture.

The standard evolutionary picture tells us that evolution is messy, incomplete and inefficient. DNA consists of many kinds of sequences. Some sequences have a bonafide biological function in that they are transcribed and then translated into proteins that have a clear physiological role. Then there are sequences which are only transcribed into RNA which doesnt do anything. There are also sequences which are only bound by DNA-binding proteins (which was one of the definitions of functional the ENCODE scientists subscribed to). Finally, there are sequences which dont do anything at all. Many of these sequences consist of pseudogenes and transposons and are defective and dysfunctional genes from viruses and other genetic flotsam, inserted into our genome through our long, imperfect and promiscuous genetic history. If we can appreciate that evolution is a flawed, piecemeal, inefficient and patchwork process, we should not be surprised to find this diversity of sequences with varying degrees of function or with no function in our genome.

The reason why most of these useless pieces have not been weeded out is simply because there was no need to. We should remember that evolution does not work toward a best possible outcome, it can only do the best with what it already has. Its too much of a risk and too much work to get rid of all these defective and non-functional sequences if they arent a burden; the work of simply duplicating these sequences is much lesser than that of getting rid of them. Thus the sequences hung around in our long evolutionary history and got passed on. The fact that they may not serve any function at all would be perfectively consistent with a haphazard natural mechanism depending on chance and the tacking on of non-functionality to useful functions simply as extra baggage.

There are two other facts in my view which should make it very easy for us to accept the existence of junk DNA. Consider that the salamander genome is ten times the size of the human genome. Now this implies two possibilities; either salamanders have ten times functional DNA than we do, or that the main difference between us and salamanders is that they have much more junk DNA. Wouldnt the complexity of salamander anatomy of physiology be vastly different if they really had so much more functional DNA? On the contrary, wouldnt the relative simplicity of salamanders compared to humans be much more consistent with just varying degrees of junk DNA? Which explanation sounds more plausible?

The third reason for accepting the reality of junk DNA is to simply think about mutational load. Our genomes, as of other organisms, have undergone lots of mutations during evolution. What would be the consequences if 90% of our genome were really functional and had undergone mutations? How would we have survived and flourished with such a high mutation rate? On the other hand, its much simpler to understand our survival if we assume that most mutations that happen in our genome happen in junk DNA.

As a summary then, we should be surprised to find someone who says they are surprised by junk DNA. Even someone like me who is not an expert can think of at least three simple reasons to like junk DNA:

1. The understanding that evolution is an inherently messy and inefficient process that often produces junk. This junk may be retained if its not causing trouble.

Continued here:
Three reasons why junk DNA makes evolutionary sense

Researchers show that DNA supercoils are dynamic structures that can hop long distances, a phenomenon that could affect gene regulation.

Scientists understanding of how long strings of DNA are packaged into tiny spaces just got a little more complicated. New research on single molecules of DNA show that supercoilssegments of extra-twisted loops of DNAcan moving by jumping along a DNA strand. The results, published today (September 13) in Science, give researchers new insights into DNA organization and point to a surprisingly speedy mechanism of gene regulation inside cells.

This is the first study that addresses the dynamics of DNA supercoils, said Ralf Seidel, who studies movement of molecular motor proteins along DNA at the University of Technology Dresden, but was not involved in the research. This supercoil hopping motion allows DNA strands to transmit supercoiling, bringing sites together in very fast manner.

DNA, being a double helix, is naturally twisted. In vivo, its packaged with proteins called histones that help condense the millions or billions of nucleotides into the small space of a cells nucleus. Constant interaction with proteins moving along the strand, like transcription factors that need to open the helix to read the DNA sequence, can affect both the double helixs twist, and the strands writhethe coiling of the strand around itself. These extra-twisted coils, called plectonemes or supercoils, form not unlike coils in phone cords. By bringing together distant segments of DNA, such as regulatory elements and the genes they control, supercoiling can affect expression.

In order to get a better sense of how supercoils behave, Cees Dekker at Delft University of Technology and his colleagues induced supercoils in single strands of DNA molecules, labeled with fluorescent dye. One end of the DNA was anchored to the side of a glass capillary tube and a magnetic bead was attached to the other end. This allowed the researchers to use miniscule magnets to twist the DNA and induce supercoils, and watch their movement using fluorescence microscopy.

Unexpectedly, the team found that supercoils move along DNA strands in one of two ways. Sometimes they slowly diffuse along the strand; other times, the supercoils hoppeddisappearing suddenly from one location while simultaneously appearing at a distant location further down the strand.

This is far more complicated than diffusion of supercoils down the DNAs length, said Prashant Purohit, who studies DNA behavior at the University of Pennsylvania, but was not involved in the study. The DNA is behaving non-locally, he noted. It shows that writhethe coiling of the DNA strandis a global, not local quantity [of the strand].

So far the intriguing phenomenon has only been observed on single strands of naked DNA, Seidel cautioned, so its unclear how supercoils might act in vivo, when the DNA is well-packaged and studded with proteins. It may be that such behavior is more important for DNA in prokaryotic cells, which have less packaged DNA than eukaryotic cells, noted Bryan Daniels, who models biological systems at the Wisconsin Institutes for Discovery at the University of Wisconsin-Madison.

The ionic environment of the cell is also likely to influence supercoiling behavior. DNA is more likely to condense in the presence of multivalent ions (3 or more positive charges), for example, than in an environment of singly-valent ions. And Dekker and his colleagues, who used singly-valent ions in their experiments, found that more supercoils formed at lower concentrations of ions.

Dekker and his team are now looking at how different DNA sequences and the presence of DNA-binding proteins can influence supercoil formation and motionthe first step toward understanding supercoil movement in vivo.

See the article here:
DNA with a Twist

A London familys DNA could be the missing link in a centuries-long quest to find the remains of King Richard III.

A team of archeologists at the University of Leicester in England exhumed a skeleton believed to be Richards beneath one of the universitys parking lots Wednesday and are hoping DNA evidence from the London family will prove their suspicions true.

Richard was killed in 1485 during the Battle of Bosworth often cited as the deciding battle in the War of the Roses by Henry Tudor VII, father of the famed King Henry VIII.

Richards Machiavellian rise to power its believed he had his nephews murdered in order to seize the thrown and short two-year reign as king is chronicled in Shakespeares play Richard III.

In 2005, British historian John Ashdown-Hill traced Richards bloodline to Joy Ibsen, a retired journalist who moved to London, Ont., from England after the Second World War and raised a family.

Ashdown-Hill discovered Ibsen and Richard shared a maternal ancestor, Cecily Neville.

Though Ibsen died in 2008, she passed the gene on to her three children: Michael, who lives in the U..K; Jeff, who lives in Toronto; and Leslie on Vancouver Island.

Its pretty exciting, said Jeff, 49. I wasnt expecting the findings to be so concise ... Im hoping that if theres a proper funeral for him, well get invited and maybe get a chance to rub elbows with some royals.

The skeleton exhumed Wednesday was found in whats believed to be the choir of the lost Church of the Grey Friars, the same place historical records indicate Richard was buried. Initial examinations found trauma to the skull consistent with a battle injury and a barbed arrow through the skeletons upper back.

Especially telling is the spinal deformity found on the exhumed skeleton. Its believed Richard had severe scoliosis, a form of spinal curvature that caused his right shoulder to appear higher than the left, the same type of curvature found on the skeleton.

Read more:
DNA could help ID a king

Video will begin in 5 seconds.

Archaeologists from the University of Leicester uncover remains that could be those of England's 15th century King Richard III.

It seems a most unlikely resting place for a King of England.

Buried under a car park behind a block of council offices, the skeletal remains of a man were discovered in the British city of Leicester this week, with a metal arrow lodged in its back and wrapped simply in a shroud.

And a Canadian-born furniture maker could help prove what archaeologists are hoping is true - that this is the lost skeleton of King Richard III.

Heir in there? ... Canadian furniture maker Michael Ibsen takes a DNA test at the site of the archaeological discovery. Photo: ITV screengrab

For the past decade, University of Leicester archaeologists, dubbed the Time Tomb Team, have been leading a search for the lost grave of the much-maligned king.

Advertisement

Richard III, who had a reputation as a murderous "hunchback" in medieval times, was killed in one of the most important clashes in English history, the Battle Of Bosworth, in 1485.

What is known is that his body was stripped and brought to Leicester, where he was buried in the church of the Franciscan Friary, known as the Grey Friars.

Read the original post:
DNA to test heir claim

DNA on a cigarette butt found outside Lloyd Rayney's home around the time of his wife's murder matched a person 'well known to police', murder trial told.

Lloyd Rayney dodges witches hats to get to court for day 31 of his murder trial. PICTURE: Kerris Berrington Source: PerthNow

Sen-Const Warren Wheatley. Source: PerthNow

LAWYERS acting for barrister Lloyd Rayney today told the Supreme Court that DNA on a cigarette butt found by police outside the family home in Como matched that of a person "well known to police" as other witnesses told of "blood curdling" screams coming from Kings Park on the night Mr Rayney's wife Corryn disappeared.

In a new twist in the long-running trial, defence lawyer David Edwardson, QC, told trial judge Justice Brian Martin that the person whose DNA was found on the cigarette butt had the same surname - Eades - as the driver of a car which was stopped by Kensington police in Manning at about 9.10pm on August 7, 2007, the night Mrs Rayney was last seen alive.

"Your honour will hear evidence shortly that a cigarette butt was retrieved and that the DNA on that cigarette matched a person well known to police by the name of Eades," he said.

The cigarette butt was among items collected by police from the footpath and verge of the Rayney home on August 22, 2007.

Mr Edwardson's comments came as a former police officer, Darrel McLeod, gave evidence at Mr Rayney's murder trial today.

It has been alleged Mr Rayney killed his wife at the family home after she arrived home from a boot scooting class in Bentley.

He has pleaded not guilty to the charge and also to an alternative charge of manslaughter.

Excerpt from:
DNA cigarette butt twist in Rayney trial

There was an extremely strong chance DNA found inside the underpants of a five-year-old girl came from the man accused of abusing her, a court has heard.

But the ACT Supreme Court has been told tests for saliva turned up nothing, despite the girls allegation her step-grandfather licked her vagina.

And the court has heard tests werent carried out on other items of clothing and bedding because they were likely to be covered in his DNA and have no probative value.

The underpants were also placed in the same bag as another item of clothing, prompting the defence to suggest the DNA might have transferred from one to the other.

Advertisement

The 61-year-old man, who cannot be named, is on trial in front of Justice Richard Refshauge accused of two counts of having sexual intercourse with a child.

He has pleaded not guilty, and also denies two alternative charges of committing acts of indecency on the girl.

It is alleged he licked the girls vagina twice when he was babysitting her in April 2009.

The allegations came to light after the girls mother picked her up, when the girl asked her mother if she could tell her the secret she shared with poppy.

The accused man entered the witness box this afternoon and denied any wrongdoing, describing his shock when police confronted him with the allegations.

Go here to see the original:
Court hears DNA findings in child sex case

By Jen Wieczner

Now that scientists have revealed that the huge swaths of genetic code once dismissed as junk DNA are not so worthless, investors may wonder if theres similar hidden value in the biotech sector. The short answer: maybe.

Though analysts say its too soon to tell what impact the discovery will have on stocks, the recent breakthrough may eventually lead to new techniques for the early detection of diseases and to the development of new drugs. And that could be a boon to firms at the forefront of biotechnology and molecular diagnostics.

Even before the findings from the project known as Encode emerged, the biotechnology sector was already on the cutting edge, at least in terms of market performance: The iShares Nasdaq Biotechnology Index ETF /quotes/zigman/85342/quotes/nls/ibb IBB -0.0072% is up more than 47% over the past 12 months, with double the returns of the broader S&P Healthcare Index. But this latest discovery suggests there could be even more promising returns ahead. The new understanding of junk DNA may help science-driven pharmaceutical companies figure out which genetic proteins can be treated with drugs, lead diagnostics companies to which genetic variations are red flags for certain diseases and help other firms evaluate the effectiveness of their treatments, says Dr. Thomas Gingeras, the head of functional genomics at Cold Spring Harbor Laboratory and one of the principal investigators for the Encode project.

This junk DNA is just another layer of complexity, but it also brings us a little bit closer to having a more full set of therapies that we can bring to patients, says Karen Andersen, a Morningstar biotechnology analyst.

It wouldnt be the first time that what scientists once considered genetic trash turned into corporate treasure. Regulus Therapeutics, a joint venture between drug companies Alnylam Pharmaceuticals /quotes/zigman/92224/quotes/nls/alny ALNY +5.00% and Isis Pharmaceuticals /quotes/zigman/74162/quotes/nls/isis ISIS +0.34% that last month began SEC proceedings to go public, focuses entirely on treating diseases through microRNAbut a decade ago, that part of the genome was also considered junk. (Regulus declined to comment.)

The new research may also bring business to Alnylam, which uses a technique known as RNA Interference to basically turn off disease-causing genes; the data could help the company identify new disease markers for which it could develop therapies, says Barry Greene, Alnylams chief operating officer. It opens up a world of biologic insight that will be helpful, says Greene. While it may take a while for companies to apply the results, the research is a step forward that might eventually lead to companies like Regulus being formed to pursue new genetic therapies: Weve never written aspects of the genome off, Greene says.

The new insight may also have positive implications for molecular diagnostics companies that are already using genomic information to test for diseases, such as Myriad Genetics /quotes/zigman/58124/quotes/nls/mygn MYGN +0.86% , which makes tests for evaluating how likely a person is to develop various types of cancer. Knowing more about the junk DNA might help the company develop more sophisticated tests to detect a disease even before it forms, says Andersen. Myriad declined to comment.

Pharmaceutical companies are also increasingly interested in harnessing our genes to create better drugs and to assess whether those drugs will work for a patient or cause side effects. A large part of the strategy at Roche /quotes/zigman/137625/quotes/nls/rhhby RHHBY -0.68% , for example, is genetic research, which the company uses to create diagnostic tests to go along with each of its drugs, in an effort to deliver more personalized health care. Sixty percent of the drugs in the firms pipeline are now paired with a test, including treatments it is developing for schizophrenia and Alzheimers disease. Roche was not available to comment before press time.

Another type of genetic science known as epigeneticswhich relates to how a gene is expressedis becoming popular with pharmaceutical companies, who are using the concept to create new drugs that can virtually alter a persons genetic instructions, says Andersen. Celgene /quotes/zigman/69584/quotes/nls/celg CELG +0.50% , for one, racked up about $700 million last year in sales of its drug Vidaza, which treats some forms of anemia and leukemia by helping bone marrow produce normal blood cells instead of unhealthy ones.

Read the original post:
Investing in ‘junk DNA’

MADISON, Wis.--(BUSINESS WIRE)--

Forensic DNA professionals confront many challenges: cold case investigations, DNA backlogs and new applications like rapid DNA and kinship DNA testing. The 23rd International Symposium on Human Identification (ISHI) presents forensic professionals with an opportunity to learn about these and other developing forensic DNA technologies alongside fellow scientists, law enforcement professionals and forensic experts. This years ISHI will be held October 15-18 in Nashville, Tennessee at the Gaylord Opryland Resort.

As the largest conference on DNA analysis for human identification, the symposium attracts more than 800 DNA analysts and forensic scientists from around the world, providing these professionals an opportunity to explore and debate the latest research, technologies and ethical issues in the industry today. This years presenters and topics include:

Author and Educator Douglas Starr

Co-director of Boston Universitys graduate program in Science and Medical Journalism and author of Gold Dagger award-winning book The Little Killer of Shepherds: A True Crime Story and the Birth of Forensic Science, Starr is this years keynote speaker. In his latest book, Starr tells the story of forensic sciences 19th century pioneers and the notorious serial killer they caught and convicted using their new scientific techniques. Winner of the Gold Dagger award in the U.K. and a finalist for the Edgar Allen Poe award in the U.S., the book received laudatory reviews, including an Editors Choice listing in the New York Times Book Review and a place on the True Crime Bestseller lists of the Wall Street Journal and Library Journal.

SNA International Founder Amanda Sozer

SNA International lends expertise to forensic labs and mass fatality identification projects. Founder and President Amanda Sozer, who received recognition for her outstanding efforts during 9/11 and Hurricane Katrina, will be leading a workshop on forensic science and human rights at ISHI. The workshop will include speakers who have worked on human rights projects as well as a presentation on the AAAS Guidelines for Scientists and Human Rights Organizations, developed by a group of collaborating scientists and representatives of human right organizations. The guidelines are designed to be helpful to those establishing science and human rights partnerships and to facilitate and promote cooperation between scientists and human rights organizations seeking scientific expertise.

Sequencing the Black Death Genome: Hendrik Poinar

Hendrik Poinar and his colleagues at McMaster University in Hamilton, Ontario, Canada developed a technique to find and sequence the Black Death genome using the skeletal remains of its victims. The possibility of environmental contamination was high. To address this, Poinar and his team extracted the DNA using a molecular probe made from a modern strain of DNA, testing this new technique on approximately 100 samples of teeth and bone excavated from a London plague pit. The result was a strain of Y. pestis unlike any known today: the Black Death. Poinar will share details of this process during his talk at ISHI.

Workshops: DNA Backlog Reduction, Cold Case Investigative Techniques

Read more from the original source:
2012 International Symposium on Human Identification Features Emerging and Best Practice Forensic DNA Techniques ...