Daily Archives: October 3, 2012

Cellectis Publishes Results Paving the Way for New Therapeutic Approaches against Cancer and Genetic Diseases

Posted: October 3, 2012 at 9:19 pm

PARIS--(BUSINESS WIRE)--

Regulatory News:

Cellectis (ALCLS.PA), the French genome engineering specialist, announces in the Journal of Biological Chemistry, one of the most respected scientific journals in the world, the publication of a new approach regarding the targeted modification of DNA2. The manuscript unmasks novel perspectives and broadens the scope of TALENsTM technology to new therapeutic approaches to fight against cancer and genetic diseases. Until now, TALENsTM, the molecular scissors created by Cellectis Group, were only able to target certain parts of the genome. A team of the Groups researchers, led by Julien Valton and Philippe Duchateau, was able to overcome this constraint, opening the way to a wider range of applications, especially in the therapeutic field.

This study, the first to be published on TALENsTM, was awarded by the selection committee of the JBC as Paper of the Week.

Since their identification in 2009, TALEs have quickly emerged as the new generation of DNA-binding domain with programmable specificity and have been successfully used to generate the molecular scissors known as TALENsTM. However, their sensitivity to methylation, a ubiquitous modification of DNA, represents a major bottleneck for their widespread utilization in the genome engineering and therapeutic fields. Using a combination of biochemical, structural and cellular approaches, the R&D department of Cellectis was able to identify the basis of such sensitivity and more importantly, to propose an efficient and universal method to overcome it.

These results are proof of the scientific creativity and quality of our research teams, as well as the power of our genome engineering tools. This new publication strengthens the relevance of our investment in TALEstechnology, and confirms our strategy within the therapeutic field, declared Andr Choulika, Chief Executive Officer of Cellectis Group.

2) Overcoming TALE DNA Binding Domain Sensitivity to Cytosine Methylation Julien Valton, Aurelie Dupuy, Fayza Daboussi, Severine Thomas, Alan Marechal, Rachel Macmaster, Kevin Melliand, Alexandre Juillerat and Philippe Duchateau J. Biol. Chem. jbc.C112.408864. First Published on September 26, 2012, doi:10.1074/jbc.C112.408864

About Cellectis

Founded in France in 1999, the Cellectis Group is based on a highly specific DNA engineering technology. Its application sectors are human health, agriculture and bio-energies. Co-created by Andr Choulika, its Chief Executive Officer, Cellectis is today one of the world leading companies in the field of genome engineering. The Group has a workforce of 230 employees working on 5 sites worldwide: Paris & Evry in France, Gothenburg in Sweden, St Paul (Minnesota) & Cambridge (Massachusetts) in the United States. Cellectis achieved in 2011 16M revenues and has signed more than 80 industrial agreements with pharmaceutical laboratories, agrochemical and biotechnology companies since its inception. AFM, Dupont, BASF, Bayer, Total, Limagrain, Novo Nordisk are some of the Groups clients and partners.

Since 2007, Cellectis has been listed on NYSE-Euronext Alternext market (ALCLS.PA) in Paris.

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Free Engine

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According to UC Berkeley professor Ignacio Chapela, the passage of Proposition 37 will not only restore the right to choose what foods we put in our bodies, but it may restore scientific process to its rightful placesomething the bioengineering industry, with full assistance from the White House, removed.

"The promises made by genetic engineering have not been fulfilled," explains Chapela, a microbial biologist who was first to exposed the fact that genetically engineered corn was contaminating ancient strains of Mexican maize via cross-pollinating. "Genetic engineering has proven to be wishful thinking, a dream that has failed."

Chapela considers himself fortunate to be able to speak out freely about GMO failings, since so many other scientists have been attacked or threatened or have lost employment for approaching genetic engineering with a critical eye. "I would like to speak for those scientists," says Chapela, "because they cannot." When the first Bush administration instructed federal regulatory bodies to step aside and give the GE industry free reign, Chapela explains, there was no scientific scrutiny allowed.

"It has been very hard to survive as a scientist who is a critical thinker now," Chapela says. "The central dogma embedded in K-12 science textbooks indoctrinates young people to accept that genetic engineering is an inevitable part of life. It says all living things are driven by genes encoded in DNA, and that by manipulating that DNA we can create life, and mix, match and alter it the way we want it." But this isn't the way it actually plays out, says Chapela. "The reality is that genetic engineering is not working, any way you look at it."

What Proposition 37 offers consumers is the promise that all GMO foods will be labeled in California. What it offers scientists is a chance to scrutinize an industry that has intimidated themsometimes to the point of ruining their careersfor questioning the validity of genetic engineering. "The Bush administration decided in the 1980s that genetic engineering was the next wave of economic development for the U.S. and for the world," says Chapela. "We were instructed to look the other way."

Labeling GE foods may help science, which at present cannot investigate whether GE food consumption is related to rises in disease. "We have been sitting here in the dark, forbidden from looking," says Chapela, who believes a GMO-labeling law will give us "the simple capacity to know and to do the science for the first time. I think we deserve it."

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The GM Barnyard

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Allergen-free cows milk and pigs with hardened arteries illustrate how the accuracy of genetic engineering has improved.

Two unsuspecting farm animals have helped to demonstrate the increasing accuracy of genetic engineering techniques. The first is a cow that produced hypoallergenic milk after researchers used RNA interference to block the production of an allergy-inducing protein, as reported this week (October 2) in Proceedings of the National Academy of Sciences. The second, reported in another paper in the same issue, is a pig that could be a model for atherosclerosis after researchers used an enzyme called a TALEN to silence a gene that helps to remove cholesterol.

Researchers have long struggled to remove cow milks allergy-inducing protein, beta-lactoglobulin, which can cause diarrhea and vomiting in children. They were previously unable to introduce foreign genes precisely enough, however, so they could never quite successfully replace the gene that codes for beta-lactoglobulin with a defective form.

But scientists at AgResearch in Hamilton, New Zealand, worked with molecules that interfere with messenger RNA (mRNA), which helps translate genes into proteins. They found microRNA (miRNA) in mice that targeted beta-lactoglobulin mRNA, so they inserted DNA encoding a version of this miRNA into the genomes of cow embryos. Out of 100 embryos, one calf produced beta-globulin-free milk. This isnt a quick process, Stefan Wagner, a molecular biologist at AgResearch, told Nature. One problem is that RNA interference cant eliminate the protein completely because some mRNA slips through.

Another technique could speed up the process. TALENs are enzymes that target and cut out a specific DNA sequence from the genome. As the break is repaired, mutations are introduced that scramble the targeted gene, leaving it unable to function.

The TALEN technology is staggeringly easy, quick, and leaves no mark in the genome, researcher Bruce Whitelaw, told Nature. Whitelaw, a molecular biologist at the Roslin Institute near Edinburgh, United Kingdom, used TALENs to disrupt genes encoding low-density lipoprotein (LDL) receptors in pigs. Without those receptors, which remove LDL from the blood, Whitelaws pigs develop atherosclerotic arteries. Such pigs could be reliable models for biomedical researchers studying human atherosclerosis.

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The GM Barnyard

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Study Says Genetics Of Intelligence Remains A Riddle, For Now

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October 3, 2012

April Flowers for redOrbit.com Your Universe Online

Your intelligence like almost all other traits is a gift from your parents, at least in part. Scientists have known for a long time that intelligence is at least partially inherited through genetics. According to psychological scientist Christopher Chabris, however, it may be some time before researchers can identify the specific genetic roots of intelligence.

A new study from Union College shows that the genes long thought to be linked to intellectual prowess actually appear to have no bearing on ones IQ, complicating scientific endeavors to get to the root of the genetics of intelligence.

An international team of researchers including Harvard economist David Laibson used large data sets that included both intelligence testing and genetic data to examine a dozen genes. In almost every case, the team found that IQ could not be linked to the specific genes that were tested.

In all of our tests we only found one gene that appeared to be associated with intelligence, and it was a very small effect. This does not mean intelligence does not have a genetic component. It means its a lot harder to find the particular genes, or the particular genetic variants, that influence the differences in intelligence, said Chabris. The results of this new study were published online in the journal Psychological Science.

Previous studies of identical and fraternal twins informed and bolstered the notion that intelligence is a heritable trait. This new research validates that conclusion, yet the exact parameters of the genetics of intelligence remain a mystery. The team asserts that the older studies, which picked out specific genes, had flaws because of the technological limits of the time. Those limits prevented researchers from probing more than a few locations in the human genome to find genes that affected intelligence.

We want to emphasize that we are not saying the people who did earlier research in this area were foolish or wrong, Chabris said. They were using the best technology and information they had available. At the time, it was believed that individual genes would have a much larger effect they were expecting to find genes that might each account for several IQ points.

The team says that much more research is needed to determine the exact role that genes play in intelligence.

As is the case with other traits, like height, there are probably thousands of genes and their variants that are associated with intelligence, he said. And there may be other genetic effects beyond the single gene effects. There could be interactions among genes, or interactions between genes and the environment. Our results show that the way researchers have been looking for genes that may be related to intelligence the candidate gene method is fairly likely to result in false positives, so other methods should be used.

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Myriad Genetics Sponsors Cancer Awareness Initiatives in Support of National Hereditary Breast and Ovarian Cancer Week

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SALT LAKE CITY, Oct. 3, 2012 (GLOBE NEWSWIRE) -- Myriad Genetics, Inc. (MYGN) today announced that, in support of National Hereditary Breast and Ovarian Cancer (HBOC) Week and National Previvor Day, it has launched an online quiz to help people assess their risk for hereditary cancers. The Hereditary Cancer Quiz is available online at http://www.hereditarycancerquiz.com. In addition, the company is providing financial support toward educational and awareness initiatives to three advocacy organizations-Bright Pink, the National Ovarian Cancer Coalition (NOCC) and Living Beyond Breast Cancer (LBBC).

HBOC Week marks the transition between National Ovarian Cancer Awareness Month and National Breast Cancer Awareness Month and was established by U.S. Congressional resolution in 2010 to raise awareness about hereditary cancer. National Previvor Day raises awareness for those individuals who have a known gene mutation or a strong family history of cancer but have not yet developed cancer.

"Understanding their risk for hereditary cancers, such as breast and ovarian cancer, is critical to helping patients make informed decisions about treatment and prevention. Our hereditary cancer risk quiz empowers patients to understand their family history and provides a framework for an informative discussion with a healthcare professional," said Mark Capone, President, Myriad Genetic Laboratories. "In addition, organizations such as Bright Pink, NOCC and Living Beyond Breast Cancer offer hereditary cancer patients and their families vital support and information in their fight against these diseases, and we are proud to support their efforts."

"Funding from Myriad and our other partner companies assists our organization in offering better and more valuable resources to hereditary cancer patients and their families," said David Barley, Chief Executive Officer, National Ovarian Cancer Coalition. "We are proud to work with Myriad, as they play a major role in the understanding and diagnosis of a person's hereditary risk for cancer."

About Hereditary Cancer

Hereditary cancers, also called inherited cancers, are those caused by genetic mutations that are passed from parent to child. These mutations predispose people to developing a particular type of cancer. Mutations in BRCA1 and BRCA2 genes are the most common cause of hereditary breast and ovarian cancers and can lead to male breast cancer, pancreatic cancer, prostate cancer and others. Women with a BRCA mutation are five times more likely to develop breast cancer than those without the mutation and more than ten times as likely to develop ovarian cancer1. Approximately 7%2 of breast cancer and approximately 14% 3,4,5 of invasive ovarian cancer result from inherited gene mutations.

DNA testing for BRCA mutations is done through a blood or saliva test and can indicate whether a person carries a BRCA gene mutation. Testing is recommended for people with certain personal and/or family history pattern, including:

Myriad Genetics is a pioneer in hereditary cancer testing and offers tests for a variety of hereditary cancer syndromes, including BRACAnalysis(R), which detects mutations in the BRCA1 and BRCA2 genes. This test has become the standard of care in identification of individuals with hereditary breast and ovarian cancer. Nearly one million patients have benefited from Myriad's hereditary cancer testing.

About Myriad Genetics

Myriad Genetics is a leading molecular diagnostic company dedicated to making a difference in patients' lives through the discovery and commercialization of transformative tests to assess a person's risk of developing disease, guide treatment decisions and assess risk of disease progression and recurrence. Myriad's portfolio of molecular diagnostic tests are based on an understanding of the role genes play in human disease and were developed with a commitment to improving an individual's decision making process for monitoring and treating disease. Myriad is focused on strategic directives to introduce new products, including companion diagnostics, as well as expanding internationally. For more information on how Myriad is making a difference, please visit the Company's website: http://www.myriad.com

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DNA construction technology makes genetic engineering cheaper, faster

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Sequencing, splicing and expressing DNA may seem to be the quintessence of cutting-edge scienceindeed DNA manipulation has revolutionized fields such as biofuels, chemicals and medicine. But in fact, the actual process can still be tedious and labor-intensive, something Lawrence Berkeley National Laboratory (Berkeley Lab) scientist Nathan Hillson learned the hard way.

After struggling for two days to design a protocol to put together a genetic circuit with 10 pieces of DNAusing a spreadsheet as his primary toolhe was dismayed to discover that an outside company could have done the whole thing, including parts and labor, for lower cost than him ordering the oligonucleotides himself. "I learned two things: one, I never wanted to go through that process again, and two, it's extremely important to do the cost-effectiveness calculation," said Hillson, a biochemist who also directs the synthetic biology program at the Berkeley Lab-led Joint BioEnergy Institute (JBEI). "So that was the genesis of the j5 software. This is the perfect thing to teach a computer to do."

The j5 software package, which has attracted users from more than 250 institutions worldwide since it was made available last year, is now the basis for the latest startup to emerge from JBEI, a Department of Energy research center established in 2007 to pursue breakthroughs in the production of cellulosic biofuels. By building on j5 and adding modules for commercial users, TeselaGen Biotechnology, founded by Hillson and two partners, says it will significantly reduce the time and cost involved with DNA synthesis and cloning, a multibillion-dollar market.

"It's like AutoCAD for biology," said TeselaGen co-founder and CEO Mike Fero. "Modern cloning is a computational problem. We are the missing informatic piece to making modern scarless DNA assembly methods a reality for the majority of biologists. Otherwise it's a small cadre of people who can do it."

Recombinant DNA assemblies are critical tools in a number of scientific pursuits: for understanding how cells are altered in diseases such as cancer, for building better antibiotics, for converting plant biomass to biofuels and for basic scientific understanding of cellular pathways. Standard cloning techniques have been in use for 40 years and are still the industry standard.

"Our biggest competition is traditional cloning, or inertia," said Fero, who was a particle physicist for 10 years before pursuing a career in biotech. "We have to make it so easy people will happily switch to the newer methods."

TeselaGen licensed j5 from Berkeley Lab, the lead institutional partner of JBEI, and currently has more than 100 scientists and engineers from large industrial and pharmaceutical companies in private beta.

"We are so pleased with the startup of TeselaGen, based on a deceptively simple idea but clearly providing a solution to a very difficult problem," said Cheryl Fragiadakis, director of technology transfer at Berkeley Lab. "It is a great example as well of a company coming out of our JBEI activities.The Lab's Tech Transfer encourages and supports entrepreneurial ventures, providing education and networking for our scientists, as a great way to get technologies out for the benefit of society."

The cloud-based software not only designs DNA construction protocols, it will compare methods to determine the one that is most cost-effective, weighing, for example, if it is cheaper to outsource a portion of the DNA construction.The more complex the task, the more time and money the program can save. The greatest savings are with combinatorial libraries, collections of hundreds to millions of related DNA assemblies, each with a different combination of genes or parts that perform similar functions in different organisms.

For example, simple construction of a metabolic pathway that takes two and a half weeks and costs $1,400 using traditional cloning can be cut down to two weeks and less than half the cost with j5. A more complex task of constructing a combinatorial protein library (with 243 constructs) would drop from $122,000 and 11 months with traditional cloning to under $30,000 and 1.5 months with j5. The same task using direct DNA synthesis would cost $538,000 and take 2.3 months.

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DNA Helps Locate Cold Case Murder Suspect

Posted: at 9:19 pm

October 3, 2012 Updated Oct 3, 2012 at 2:52 PM EDT

Miami County, Ind. (Indianas NewsCenter) DNA evidence plays a key role in helping authorities make an arrest in a 20-year-old murder case.

The Miami County Prosecutors Office announced Wednesday Timothy J. Jimerson of Biloxi, Mississippi was arrested in connection to the cold case murder of Toni Spicer, who was found murdered in her mobile home in the southern part of Miami County, all thanks to DNA evidence collected 20 years ago.

Prosecutor Bruce Embrey says that due to the very detailed and thorough crime scene investigation performed by Sgt. Dean Marks and State Trooper Gary Boyles in 1992, police agencies at any time could help in the murder investigation.

The evidence collected from the scene was sent off for DNA examination and cataloging, awaiting a DNA hit so that a suspects name could be issued. But it wasnt until recently that a DNA match was found.

Since a DNA match in most cases isnt enough to identify a suspect, the help of the Biloxi, Mississippi Police Department was enlisted and after extensive investigation Jimerson was arrested and is now awaiting extradition back to Peru.

Copyright 2012 A Granite Broadcasting Station. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.

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DNA on gun matches Thompson’s, expert testifies at trial

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DNA found on the gun allegedly used to murder a Dartmouth taxi driver matches that of Chaze Lamar Thompson, a Halifax jury was told Tuesday.

Michelle Fisher, an expert in forensic DNA analysis, testified that theres a one-in-79-million chance that DNA swabbed from the grip of the gun belongs to a black Canadian other than Thompson.

The 22-year-old Thompson is on trial in Nova Scotia Supreme Court for first-degree murder in the death of Sergei Kostin, a driver for Bobs Taxi.

Thompson, of Dartmouth, is accused of shooting Kostin in the head from the back seat of his cab on Johnson Road in Cherry Brook on the afternoon of Jan. 17, 2009.

Kostins burned-out cab was discovered three days later, parked in woods at the end of Downey Road in North Preston.

His body was found that April 1 under the roots of a fallen tree along Upper Governor Street in North Preston.

Wayne McAvoy, Thompsons first cousin, led police to the body and was given immunity from prosecution after agreeing to testify for the Crown.

McAvoy said a gun found by police at Thompsons sisters apartment in Dartmouth in February 2009 was the murder weapon.

Part of the gun was in a couch and part was by a refrigerator.

Fisher testified Tuesday that of five swabs taken from the gun, only one was suitable for a meaningful comparison. The swab was from both sides of the guns grip.

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Woman charged in husband's death gives DNA sample

Posted: at 9:18 pm

LOS ANGELES (AP) -- A nationally known professional tennis referee charged with the coffee-cup killing of her husband gave police a DNA sample Wednesday after dropping her opposition to the procedure.

Lois Ann Goodman, 70, who is charged with beating her husband to death with the cup last April, was accompanied by about 25 supporters, including friends and relatives, when she appeared briefly in court for a pretrial hearing.

A judge scheduled Goodman's next hearing for Nov. 8.

In the meantime, defense attorneys say they have a huge amount of evidence and court documents provided by prosecutors to review before a trial is scheduled. They also demanded to see original notes taken at Goodman's home by police officers who initially ruled the case an accidental death. In addition, they are seeking notes and recordings from coroner's investigators and the mortician who examined the body.

Goodman was arrested in August just before she was to referee at match at the U.S. Open.

Her attorneys say her 80-year-old husband was the victim of a freak accident.

Authorities initially believed Alan Goodman fell down stairs at home while she was away but later decided it was homicide. Prosecutors now believe he was struck 10 times on the head and stabbed with the broken cup.

The couple was married nearly 50 years with three grown children.

Defense attorneys Alison Triessl and Robert Sheahen told reporters that they anticipate surprise revelations in the case after all of the discovery materials are reviewed. They had opposed having Goodman provide a DNA sample but relented after losing an appeal on the issue.

''No DNA sample is going to prove anything,'' said Sheahen. ''Proving that her DNA is in her own home is ridiculous.''

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Inherited Diseases Found Sooner in Newborns With DNA Scan

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Scanning the DNA of sick infants using a new speed-reading method can diagnose rare genetic disorders in two days instead of weeks, according to research that brings gene mapping a step closer to everyday hospital use.

Researchers at Childrens Mercy Hospitals and Clinics in Kansas City, Missouri, created software that takes raw data from DNA scanning machines and combs though hundreds of genetic disorders to spot disease-causing mutations. The system provided likely diagnoses for three of four sick babies in about two days, results published in Science Translational Medicine found.

The new method has the potential to make genome sequencing practical for neonatal intensive care units, enabling doctors to diagnose mysterious genetic diseases more quickly, said Stephen Kingsmore, director of the Center for Pediatric Genomic Medicine at Childrens Mercy and a study senior author. Fast diagnoses of sick babies could lead to life-extending treatments sooner in some or help avoid futile, costly therapies in others.

This is the biggest breakthrough in this technology for clinical applications we have seen in a few years, said David Dimmock, a geneticist at the Medical College of Wisconsin and Childrens Hospital of Wisconsin in Milwaukee, who wasnt involved in the study. The ability to sequence and interpret a genome in less than week is huge.

Dimmock said researchers at his institution were working on a similar fast genome interpretation system, but hadnt published the results yet. They beat us to the punch, he said.

There are about 3,500 known genetic diseases of which 500 have treatments, Kingsmore said. Many of these genetic illnesses hit young kids. Roughly 20 percent of infant deaths are caused by genetic conditions, according to the study released today.

The Childrens Mercy Hospital system was made possible in part by a new sequencing machine developed by San Diego-based Illumina Inc. (ILMN) that can decode an entire DNA sequence of a person in one day. This generates a colossal volume of raw data that must be analyzed by expert genetic researchers, a process that previously has taken weeks or months.

Heres where the system devised by Childrens Mercy researchers comes into play. Kingsmore and his team devised smart software that allows treating doctors to enter in a sick babys symptoms. The software then matches these reported symptoms to known genetic diseases that have similar symptoms, and scans through the babys genome results for likely harmful mutations in relevant genes.

We think this is going to transform the world of neonatology, Kingsmore said during a conference call with reporters. Until now, this was just not possible to get whole genome scan results quickly enough to help sick newborns in intensive care units, he said. Babies either died or else got better and were discharged home before the results of a gene test were returned.

For cases in which treatments are available, spotting the cause of a disease sooner may allow treatments to be started before it is too late, he said. Kingsmore estimated the total cost of the test to be about $13,500.

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