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Category Archives: Human Genetic Engineering

Virginia Tech to tackle the 'Big Data' challenges of next-generation sequencing with HokieSpeed

Wu Feng, associate professor of computer science in the College of Engineering at Virginia Tech, will engage in Big Data research with promising advances for genomics. Credit: Virginia Tech

The National Science Foundation (NSF) and the National Institutes of Health (NIH) today announced nearly $15 million in new big data fundamental research projects. These awards aim to develop new tools and methods to extract and use knowledge from collections of large data sets to accelerate progress in science and engineering research.

Among the awards is a $2 million grant to Iowa State, Virginia Tech, and Stanford University to develop high-performance computing techniques on massively parallel heterogeneous computing resources for large-scale data analytics.

Such heterogeneous computing resources include the NSF Major Research Instrumentation (MRI) funded HokieSpeed supercomputing instrument with in-situ visualization. HokieSpeed was the highest-ranked commodity supercomputer in the U.S. on the Green500 when it debuted in November 2011.

Specifically, the three-university team intends to develop techniques that would enable researchers to innovatively leverage high-performance computing to analyze the data deluge of high-throughput DNA sequencing, also known as next generation sequencing (NGS).

The research will be conducted in the context of grand challenge problems in human genetics and metagenomics or the study of metagenomes, the genetic material received directly from environmental samples.

On this grant, working together are Srinivas Aluru, a chaired professor of computer engineering at Iowa State University and principal investigator; Patrick S. Schnable, a chaired professor of agronomy, also at Iowa State; Oyekunle A. Olukotun, a professor of electrical engineering and computer science at Stanford University; and Wu Feng, http://www.cs.vt.edu/user/feng who holds the Turner Fellowship and who is an associate professor of computer science at Virginia Tech. Olukotun and Feng are co-principal investigators.

In previous research Aluru has advanced the assembly of plant genomes, comparative genomics, deep-sequencing data analysis, and parallel bioinformatics methods and tools. Aluru and Schnable previously worked together on generating a reference genome for the complex stalk of corn genome that will help speed efforts to develop better crop varieties.

Feng's relevant prior work lies at the synergistic intersection of life sciences and high-performance computing, particularly in the context of big data. For example, in 2007, Feng and his colleagues created an ad-hoc environment called ParaMEDIC, short for Parallel Metadata Environment for Distributed I/O and Computing, to conduct a massive sequence search over a distributed ephemeral supercomputer that enabled bioinformaticists to "identify missing genes in genomes."

Feng said, "With apologies to the movie Willy Wonka and the Chocolate Factory, one can view ParaMEDIC as WonkaVision for Scientific Data a way to intelligently teleport data using semantic-based cues. "

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Can Genetically Modified Cows Produce Allergy-Free Milk?

Got milk allergies? Then New Zealand may have a Franken-cow thats right for you!

Researchers at the University of Waikato say they have come up with a way to tinker with bovine DNA and engineer cows to produce hypoallergenic milk, according to ABC News.

The scientists essentially selected for genes that would cause the cows to make less BLG, a protein in cow milk that 23 percent of the general population is allergic to.

Milk allergies are, of course, far more serious than your garden-variety lactose intolerance. For those who are allergic to milk, reactions can range from hives to difficulty breathing, vomiting and diarrhea. (Milk allergies mostly affect young children, who typically outgrow them by age 3.)

MORE: 18 Companies That Oppose GMO Food Labeling

Dont expect hypoallergenic milk to appear in your local dairy aisle anytime soon, however. Stateside critics of the Kiwis work point out that while the GMO cows did produce far less BLG, thats probably not even the protein that causes milk allergy sufferers the most trouble in the first place.

Casein, actually, is the major milk protein that we believe causes most of the severe milk allergies, Dr. Scott Sicherer, a professor and researcher at the Jaffe Food Allergy Institute at Mount Sinai Hospital in New York, tells ABC.

And, in fact, as BLG levels dropped in the cows milk, levels of casein actually rose.

Of course, the mutant Kiwi cows are only the latest headline-maker in the controversial scientific quest to genetically engineer better cows and frankly, theyre not even the creepiest.

That dubious honor probably goes to Chinese researchers, who last year announced they had created a mutant herd of 300 dairy cows capable of producing human milk. (Air quotes abound in trying to write about genetic engineering.)

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Sigma® Life Science Launches Novel, Affordable Pluripotent Stem Cell Culture Medium

ST. LOUIS, Oct. 3, 2012 /PRNewswire/ --Sigma-Aldrich Corporation (SIAL) announced today that Sigma Life Science, its innovative biological products and services research business, has launched Stemline Pluripotent Culture Medium, a novel human pluripotent stem cell culture medium that provides a consistent environment for the long-term maintenance and growth of healthy pluripotent stem cells. The new medium performs equivalently to the industry's leading medium and provides academic and pharmaceutical stem cell research labs with a substantially lower cost alternative to higher priced media. Additional information and sample requests of the Stemline Pluripotent Culture Medium are available at http://www.sigma.com/stemlinepsc.

"The exorbitant cost of media for pluripotent stem cells is a universal complaint from the stem cell research community. Our Stemline Pluripotent Culture Medium performs equivalently to the leading medium for maintaining pluripotency and optimal growth rates, and is produced more efficiently than traditional media, resulting in lower costs. For example, a typical academic lab that consumes three 500 mL bottles of media per week could save at least $12,000 annually using our new Stemline medium. A high-throughput pharmaceutical development team that consumes 20 liters of media weekly could save more than $160,000 annually," said John Listello, Market Segment Manager for Regenerative Medicine at Sigma Life Science.

Culturing pluripotent stem cells can be challenging as many media's undefined, heterogenous mixtures can cause inconsistent growth rates and undesired spontaneous differentiation. The Stemline Pluripotent Stem Cell Culture Medium is serum-free, composed of fully-defined components and has 80% less basic fibroblast growth factor than the leading pluripotent stem cell culture medium. This provides a consistent environment for long-term maintenance of optimal growth rates, viability and pluripotency. Rigorous characterization of the Stemline Pluripotent Stem Cell Culture Medium has demonstrated that cultured pluripotent stem cells display all established pluripotency markers and maintain proper karyotype and the ability to differentiate into each of the three germ layers. The feeder-independent medium also enables culturing with synthetic matricies, thereby eliminating a source of variability that would prohibit later clinical applications.

"Academic and pharmaceutical groups performing toxicology screens, disease-specific stem cell research or studies of the basic mechanisms behind pluripotency and differentiation depend upon a steady supply of consistent, high-performance cell culture medium. This novel Stemline medium extends Sigma's existing position as one of the largest global providers of cell culture media," said Listello.

Existing Stemline stem cell culture media include specialized formulations for expansion of six human adult stem cell and progenitor cell types: hematopoietic, neural, dendritic, mesenchymal, T-cells, and keratinocytes. These six Stemline media are produced under good manufacturing practices (GMP) and have Device Master File certificates from the U.S. Food and Drug Administration.

Sigma Life Science's comprehensive stem cell product portfolio includes custom iPS cell CompoZr ZFN-mediated genetic engineering, Stemgent Reprogramming Lentiviruses, the MISSION shRNA Library with the latest content release from The RNAi Consortium, 3D matrices, growth factors, small molecules, other cell culture media and the industry's most validated antibodies. Sigma Life Science acquired a worldwide license to Kyoto University's iPS cell patent portfolio in February, 2012.

For more information and to request pricing, visit http://www.sigma.com/stemlinepsc.

Cautionary Statement: The foregoing release contains forward-looking statements that can be identified by terminology such as "could," "could expect," "can be," "predictive" or similar expressions, or by expressed or implied discussions regarding potential future revenues from products derived there from. You should not place undue reliance on these statements. Such forward-looking statements reflect the current views of management regarding future events, and involve known and unknown risks, uncertainties and other factors that may cause actual results to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that pluripotent stem cells, pluripotent stem cell media, or related custom services will assist the Company to achieve any particular levels of revenue in the future. In particular, management's expectations regarding products associated with pluripotent stem cells, pluripotent stem cell media, or related custom services could be affected by, among other things, unexpected regulatory actions or delays or government regulation generally; the Company's ability to obtain or maintain patent or other proprietary intellectual property protection; competition in general; government, industry and general public pricing pressures; the impact that the foregoing factors could have on the values attributed to the Company's assets and liabilities as recorded in its consolidated balance sheet, and other risks and factors referred to in Sigma-Aldrich's current Form 10-K on file with the US Securities and Exchange Commission. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those anticipated, believed, estimated or expected. Sigma-Aldrich is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.

About Sigma Life Science: Sigma Life Science is a Sigma-Aldrich business that represents the Company's leadership in innovative biological products and services for the global life science market and offers an array of biologically-rich products and reagents that researchers use in scientific investigation. Product areas include biomolecules, genomics and functional genomics, cells and cell-based assays, transgenics, protein assays, stem cell research, epigenetics and custom services/oligonucleotides. Sigma Life Science also provides an extensive range critical bioessentials like biochemicals, antibiotics, buffers, carbohydrates, enzymes, forensic tools, hematology and histology, nucleotides, amino acids and their derivatives, and cell culture media.

About Sigma-Aldrich: Sigma-Aldrich is a leading Life Science and High Technology company whose biochemical, organic chemical products, kits and services are used in scientific research, including genomic and proteomic research, biotechnology, pharmaceutical development, the diagnosis of disease and as key components in pharmaceutical, diagnostics and high technology manufacturing. Sigma-Aldrich customers include more than 1.3 million scientists and technologists in life science companies, university and government institutions, hospitals and industry. The Company operates in 38 countries and has nearly 9,100 employees whose objective is to provide excellent service worldwide. Sigma-Aldrich is committed to accelerating customer success through innovation and leadership in Life Science and High Technology. For more information about Sigma-Aldrich, please visit its website at http://www.sigma-aldrich.com.

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Animals engineered with pinpoint accuracy

A cow in New Zealand has been genetically modified to produce hypoallergenic milk.

AgResearch

Two genetically engineered farm animals reported today illustrate how far from Frankensteins stitched-together monster animal biotechnology has come. One of those animals, a cow, secretes milk that lacks an allergy-inducing protein because researchers accurately blocked its production using the technique of RNA interference1. And in pigs, scientists have used an enzyme called a TALEN2 to scramble a gene that would normally help remove cholesterol.

RNA interference (RNAi) and TALENs are more accurate at targeting the gene in question than are earlier genetic engineering techniques. For years, researchers tried to remove the allergy-inducing milk protein beta-lactoglobulin from cow's milk, which can cause diarrhea and vomiting in some toddlers. They tried replacing the gene encoding beta-lactoglobulin with a defective form, but this proved nearly impossible because the techniques available to introduce foreign genes into animal genomes were not precise, and misplaced genes failed to express themselves correctly.

In 2006, scientists at AgResearch in Hamilton, New Zealand began to experiment with molecules that interfere with the messenger RNA go-between that enables translation of a gene into protein. In mice, they discovered a short chunk of RNA, called a microRNA, that targeted beta-lactoglobulin messenger RNA directly to prevent its translation. They inserted DNA encoding a version of this microRNA into the genome to create genetically modified cow embryos that they hoped would grow into cows without the allergen in their milk. Out of 100 embryos, one calf yielded beta-globulin-free milk. This isnt a quick process, says Stefan Wagner, a molecular biologist at AgResearch. That's why it has taken so long to succeed in making an allergen-free cow, he says.

Wagner says that TALENs, which were not readily available when he began his research, might speed up the process, and that the team plans to use them to eliminate beta-lactoglobulin. RNAi cannot eliminate the protein completely because some messenger RNA slips past the blockade, but each TALEN targets a specific DNA sequence in the genome and cuts it. As the body repairs the break, mutations are often introduced that render the targeted gene non-functional. The TALEN technology is staggeringly easy, quick, and leaves no mark in the genome, says Bruce Whitelaw, a molecular biologist at the Roslin Institute near Edinburgh in the United Kingdom, who contributed to the work in pigs. In essence, we are just mimicking an evolutionary process with precise, man-made editors.

His team used TALENs to disrupt genes encoding low-density lipoprotein (LDL) receptors. Without these receptor proteins to remove cholesterol-containing LDLs from the blood, LDLs build-up and lead to atherosclerosis. Pigs with this condition may be reliable models of human atheroscelerosis in biomedical research.

The TALEN-modified pig is not the first model of human heart disease (see Model pigs face a messy path), but the technique makes genetic engineering less costly and more efficient. Id be exaggerating if I said that pigs and cows can now be thought of as big mice, but we are moving in that direction, says Heiner Niemann, a bioengineer at the Institute of Farm Animal Genetics in Neustadt, Germany.

The excitement surrounding these technological advances is bittersweet, however. Originally, engineered animals were produced with the aim of making food safer, healthier and more abundant. Yet despite years of investment, almost no animal has been approved by regulatory agencies around the world. Wagner says he has not tasted the milk from his special cow because hes not permitted to under New Zealand law. We must restrict our research to scientific analysis, he says. The current climate for animal biotech is not very good, and therefore, we are nowhere near getting this to the consumer."

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Animals engineered with pinpoint accuracy

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

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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The GM Barnyard

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 PNAS. 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 diarrhoea 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, UK, 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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