Scientists have created the first organism with synthetic DNA that can replicate in a cell, an achievement that promises to add new letters to the genetic code underlying life on earth.

In the natural world, just two chemical base pairs, known simply as A-T and C-G, constitute the building blocks of DNA in all life forms. Research published yesterday in the journal Nature describes the creation of a cell that contains a man-made base pair, dubbed d5SICS-dNAM.

By expanding the natural boundaries of what constitutes life, scientists hope they can one day create new proteins that can handle a variety of chores in the body, potentially leading to unique ways to attack disease. The approach is safe, the researchers said, because it includes a chemical additive that the cell needs to survive.

We created an organism that lives and stably harbors genetic information in its DNA, said Floyd Romesberg, a chemist at La Jolla, California-based Scripps Research Institute, whose laboratory created the new organism. Instead of two base pairs, it has a third.

All life on earth is based on the combination of four chemicals. Adenine bonds naturally with thymine to create the A-T section of the formula, while guanine and cytosine make up the C-G part. The joining of these base pairs in different combinations creates amino acids and proteins that power life.

Romesbergs work differs from other research in the field of genetic engineering in that it involves creation of components that are purely synthetic and integrated into the machinery of life in a cell, he said in a telephone interview.

Other scientists in the field, notably J. Craig Venter, work by constructing genetic material from natural building blocks, or natural components of DNA and proteins.

Starting in 2009, Romesberg and his laboratory created about 300 nucleotides with the newly constituted DNA before landing on ones they believed might be able to replicate in a cell. They then used a special chemical transporter to get the synthetic base pair into an E.coli cell, where it replicated without affecting cell growth. That suggests it wasnt recognized as atypical by the bodys natural DNA repair machinery, according to the paper.

Synthorx Inc., a San Diego-based biotechnology company, has exclusive rights to the synthetic biology from Scripps. The company plans to focus on developing the technology for use in vaccines, medicines and diagnostics, the company said yesterday in a statement.

The research, though promising for fields of medicine and drug development, will probably raise ethical and safety concerns, said Arthur Caplan, head of the division of bioethics at NYU Langone Medical School. He called the research promising.

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Scientists Add New Letters to Lifes Genetic Alphabet

For possibly billions of years, the DNA blueprints for life on Earth have been written with just four genetic "letters" -- A, T, G and C. On Wednesday, scientists announced that that they added two more.

In a paper published in the journal Nature, bio-engineers at Scripps Research Institute in La Jolla said they had successfully inserted two synthetic molecules into the genome of an Escherichia coli bacterium, which survived and passed on the new genetic material.

In addition to the naturally occurring nucleotides adenine, thymine, guanine and cytosine, which form the rungs of DNA's double-helix structure, the bacterium carried two more base-pair partners, which study authors have dubbed d5SICS and dNaM.

For more than a decade, scientists have been experimenting with so-called unnatural base pairs, or UBPs, saying they may hold the key to new antibiotics, future cancer drugs, improved vaccines, nanomaterials and other innovations.

Until now, however, those experiments have all been conducted in test tubes.

"These unnatural base pairs have worked beautifully in vitro, but the big challenge has been to get them working in the much more complex environment of a living cell," lead study author Denis Malyshev, a molecular and chemical biologist at Scripps, said in a prepared statement.

The new genetic material did not appear to be toxic to the bacteria, and it only remains in the organism's genome under specific lab conditions. In a natural environment, the molecules -- nucleoside triphosphates -- degrade and disappear in a day or two. Once they disappear, the bacterium reverts back to its natural base pair arrangement.

Still, experts said insertion of the synthetic materials into E. coli's genome was a milestone.

"This definitely is a significant achievement," said Ross Thyer, a synthetic biologist at the University of Texas at Austin, who was not involved in the research. "What I'm most excited about is how this will help us answer some bigger evolutionary questions: Why has life settled on a specific set of bases."

Malyshev and colleagues went about creating the semi-synthetic bacterium by genetically engineering a stretch of ring-like DNA known as a plasmid.

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Scientists add new letters to bacteria's genetic 'alphabet'

Vermont Governor Pat Shumlin intends to sign legislation requiring the labeling of foods that contain ingredients that are genetically modified (GMOs) or produced with genetic engineering. The governors office announced via Twitter that the signing will take place Thursday, May 8. Once the bill is signed, Vermont will become the first state to require mandatory GMO labeling.

The Vermont House approved the bill as amended by the Senate by a vote of 114-30 on April 24. The proposed effective date is July 1, 2016.

It is estimated that 80% of all food sold in the United States is at least partially produced from genetic engineering. The bill would require labeling on all such food sold at retail in Vermont, regardless of whether the food was manufactured in the state. Vermont lawmakers included a $1.5 million legal defense fund in the bill because they expect the law to face legal challenges after the signing.

While the bill exempts processing aids and milk from cows that have been fed GMO feed, many dairy products and other foods that incorporate milk would be affected unless they were made with organic ingredients.

New York GMO bill advances

The New York General Assemblys Committee on Consumer Affairs and Protection advanced a bill on Tuesday that would require the labeling of GMOs. The committee voted 9-6 to approve AB 3525 and now will send the bill to the Committee on Codes. The bill is similar to Vermonts legislation as it would take effect without needing the surrounding states to pass labeling bills.

The New York legislation contains the same exemptions for processing aids and milk from cows that have been fed GMO feed or treated with GMO material. The bill must be approved by both the Assembly and the state Senate before the June 19 recess date and signed by the governor before it can become law.

The Food and Drug Administration, American Medical Association, World Health Organization, USDA and the National Academy of Sciences all have said that GMO ingredients are safe and there are no negative health effects associated with their use.

The International Dairy Foods Association (IDFA) and many other trade organizations oppose individual state legislation on GMO labeling and fully supportThe Safe and Accurate Food Labeling Act of 2014introduced last month by Reps. Mike Pompeo (R-KS) and G.K. Butterfield (D-NC). This bill would preempt states from requiring mandatory labeling and establish a federal standard for voluntary labeling of food and beverage products made with GMOs.

IDFA is working with the Safe and Affordable Food Coalition, headed by the Grocery Manufacturers Association, on issues related to GMO labeling.

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Vermont governor to sign GMO labeling bill

For possibly billions of years, the DNA blueprints for life on Earth have been written with just four genetic "letters" -- A, T, G and C. On Wednesday, scientists announced that that they added two more.

In a paper published in the journal Nature, bio-engineers at Scripps Research Institute in La Jolla said they had successfully inserted two synthetic molecules into the genome of an Escherichia coli bacterium, which survived and passed on the new genetic material.

In addition to the naturally occurring nucleotides adenine, thymine, guanine and cytosine, which form the rungs of DNA's double-helix structure, the bacterium carried two more base-pair partners, which study authors have dubbed d5SICS and dNaM.

For more than a decade, scientists have been experimenting with so-called unnatural base pairs, or UBPs, saying they may hold the key to new antibiotics, future cancer drugs, improved vaccines, nanomaterials and other innovations.

Until now, however, those experiments have all been conducted in test tubes.

"These unnatural base pairs have worked beautifully in vitro, but the big challenge has been to get them working in the much more complex environment of a living cell," lead study author Denis Malyshev, a molecular and chemical biologist at Scripps, said in a prepared statement.

The new genetic material did not appear to be toxic to the bacteria, and it only remains in the organism's genome under specific lab conditions. In a natural environment, the molecules -- nucleoside triphosphates -- degrade and disappear in a day or two. Once they disappear, the bacterium reverts back to its natural base pair arrangement.

Still, experts said insertion of the synthetic materials into E. coli's genome was a milestone.

"This definitely is a significant achievement," said Ross Thyer, a synthetic biologist at the University of Texas at Austin, who was not involved in the research. "What I'm most excited about is how this will help us answer some bigger evolutionary questions: Why has life settled on a specific set of bases."

Malyshev and colleagues went about creating the semi-synthetic bacterium by genetically engineering a stretch of ring-like DNA known as a plasmid.

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Scientists add new letters to bacteria's genetic 'alphabet'

The first report of a bacterium whose genome contains man-made DNA building blocks opens the door for tailor-made organisms that could be used to produce new drugs and other products.

All living creatures have a DNA "alphabet" of just four letters, which encode instructions for the proteins that perform most of the key jobs inside cells. But expanding that alphabet to include artificial letters could give organisms the ability to produce new proteins never seen before in nature.

The man-made DNA could be used for everything from the manufacture of new drugs and vaccines to forensics,researchers say.

"What we have done is successfully store increased information in the DNA of a living cell," study leader Floyd Romesberg, a chemical biologist at The Scripps Research Institute in La Jolla, Calif., told Live Science. Yet many steps remain before Romesberg and his colleagues can get cells to produce artificial proteins. [Biomimicry: 7 Clever Technologies Inspired by Nature]

DNA alphabet

The field of synthetic biology involves tinkering with DNA to create organisms capable of novel functions in medicine, energy and other areas.

The DNA alphabet consists of four letters, or bases: adenine, thymine, guanine and cytosine (A, T, G and C). Adenine pairs with thymine, and guanine pairs with cytosine. RNA is a genetic material similar to DNA, except it has a different chemical backbone and replaces the base thymine with uracil (U).

Living things translate DNA into proteins through a series of steps. First, enzymes "transcribe" the DNA into RNA. Then, structures called ribosomes translate the DNA into proteins, which are made up of strands of molecules called amino acids.

Ultimately, the researchers aim to create organisms that can produce artificial proteins. But first, they need to show that the DNA containing the man-made letters can be transcribed into RNA, and that this RNA can be translated into proteins.

In the study, Romesberg and his team created an new pair of DNA letters not found in nature and inserted the pair into cells of Escherichia coli bacteria. Getting the DNA into the cells is not easy, but the researchers were able to do it by way of a transporter, a protein that moves materials across cell membranes.

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Weird Engineered Organism Has 6-Letter DNA

In an undated handout photo, Floyd Romesberg, a chemistry professor at the Scripps Research Institute and leader of a team that has created an organism with a partially artificial genetic code. The research, published on May 7, 2014, is likely to raise safety concerns and ethical questions, but scientists also say it could lead to medicines and industrial products that could not be made otherwise. (Scripps Research Institute via The New York Times)

The accomplishment might eventually lead to organisms that can make medicines or industrial products that cells with only the natural genetic code cannot. The scientists behind the work at the Scripps Research Institute have already formed a company to try to use the technique to develop new antibiotics, vaccines and other products, though a lot more work needs to be done before this is practical.

The work also gives some support to the concept that life can exist elsewhere in the universe using genetics different from those on Earth.

"This is the first time that you have had a living cell manage an alien genetic alphabet," said Steven A. Benner, a researcher in the field at the Foundation for Applied Molecular Evolution in Gainesville, Fla., who was not involved in the new work.

But the research, published online by the journal Nature, is bound to raise safety concerns and questions about whether humans are playing God. The new paper could intensify calls for greater regulation of the budding field known as synthetic biology, which involves the creation of biological systems intended for specific purposes.

"The arrival of this unprecedented 'alien' life form could in time have far-reaching ethical, legal and regulatory implications," Jim Thomas of the ETC Group, a Canadian advocacy organization, said in an email. "While synthetic biologists invent new ways to monkey with the fundamentals of life, governments haven't even been able to cobble together the basics of oversight, assessment or regulation for this surging field."

Despite the great diversity of life on Earth, all species, from simple bacteria to human beings, use the same genetic code. It consists of four chemical units in DNA, sometimes called nucleotides or bases, that are usually represented by the letters A, C, G and T. The sequence of these chemical units determines what proteins the cell makes. Those proteins in turn do most of the work in cells and are required for the structure, function and regulation of the body's tissues and organs.

The Scripps researchers chemically created two new nucleotides, which they called X and Y. They inserted an X-Y pair into the common bacterium E. coli. The bacteria were able to reproduce normally, though a bit more slowly than usual, replicating the X and Y along with the natural nucleotides.

In effect, the bacteria have a genetic code of six letters rather than four, perhaps allowing them to make novel proteins that could function in a completely different way from those created naturally.

"If you have a language that has a certain number of letters, you want to add letters so you can write more words and tell more stories," said Floyd E. Romesberg, a chemist at Scripps who led the work.

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Scientists Add Letters to DNA's Alphabet, Raising Hope and Fear

d27m - genetic engineering (omd cover) 2014
genetic engineering by d27m. 2014. http://www.d27m.fr.mu.

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Process - Genetic Engineering and Biotechnology

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Minecraft- Genetic Engineering Ranch Tour
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COMING SOON: Food products that contain higher levels of phytosterols for reduced cholesterol, crops with higher levels of carotenoids for increased vitamin A, potato loaded with antioxidants, low-linolenic soybean, and high-lysine corn.

These may be farfetched but the possibilities are endless. Thanks to genetic engineering, the crops of the future will no longer be just dreams but realities. Already, the world has seen eggplant and corn that defy pests, vitamin A-rich rice, herbicide tolerant soybean, virus resistant papaya, and high laureate canola.

They are called genetically modified (GM) crops, which are products of biotechnology, a "technique that makes use of organism (or parts of it) to make or modify products, to improve plants or animals, or to develop microorganisms for specific purposes."

GM crops are made through a process called genetic engineering. Dr. Antonio Alfonso, a plant breeder at the Philippine Rice Research Institute (PhilRice) and the Crops Biotechnology Center director said genetic engineering is employed because of the following reasons: the trait is not present in the germplasm of the plant; the trait is very difficult to incorporate using conventional breeding methods; and it would take a very long time to introduce and/or improve such trait in the crop through conventional breeding.

In 1994, Calgene's delayed-ripening tomato became the first GM food crop to be produced and consumed in an industrialized country. Other GM crops -- corn, soybean, cotton, canola, and eggplant -- followed. These are called "first generation" crops which have proven their ability to lower farm-level production costs.

Now, research is focused on "second generation" GM crops that will feature increased nutritional and/or industrial traits. These crops will have more direct benefits to consumers. Examples include: potatoes with higher starch content and inulin; edible vaccines in corn, banana, and potatoes; corn varieties with low phytic acid and increased essential amino acids; healthier oils from soybean and canola; and allergen-free nuts.

These are called functional foods. It is defined as "foods or dietary components that claim to provide health benefits aside from basic nutrition." These foods contain biologically active substances such as antioxidants that may lower the risks from certain diseases associated with aging.

"Diet and health are closely related," explains the International Service for the Acquisition of Agri-biotech Applications (ISAAA). "Thus crops are now being enhanced through biotechnology to increase levels of important biologically active substances for improved nutrition, to increase body's resistance to illnesses, and to remove undesirable food components."

Linoleic acid (LA), alpha-linolenic acid (ALA), and polyunsaturated fatty acids (PUFAs) are some of the essential fatty acids. These are considered essential because they cannot be synthesized by the human body. A large number of scientific research studies suggest that higher dietary essential fatty acid intakes are associated with reductions in cardiovascular disease risk.

The main food sources of the long-chain Omega-3 fatty acids are fish. Plants lack the enzymes to make long-chain fatty acids needed by human beings. Scientists at the University of Bristol modified Arabidopsis thaliana to produce long-chain PUFAs.

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Functional crops are coming

No to Genetic Engineering | People and Politics
Genetic engineering is banned in berlingen by Lake Constance. The town in Baden-Wrttemberg, a state ruled by a coalition of the Green party and the Social Democrats, is now in the vanguard...

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Korey Fung Ethics of Genetic Engineering Designer Babies Reproductive Revolution
Student Korey Fung presents "Ethics of Genetic Engineering: Designer Babies and the Reproductive Revolution" on April 8, 2014 in the Technology and Future of...

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John Sterling | 05/01/2014

The following article, reproduced in full below, was originally published at Genetic Engineering & Biotechnology News.

Its been a hot year for biotech! As G. Steven Burrill, CEO of Burrill & Co., noted in a recent report, life science firms raised $2.9 billion in new equity capital globally from public investors in February. This included $1.1 billion raised by 18 companies that completed initial public offerings and $1.8 billion raised by 23 companies that completed follow-on offerings during the month.

In the U.S., 16 life sciences companies raised $959 million through IPOs and 22 companies raised $1.75 billion through follow-on offerings on U.S. exchanges during February, making the month the biggest for IPOs in terms of the number of completed deals since February 2000!

Why the excitement? Promising new biotherapeutics are emerging from the drug pipeline. Advances in stem cell research and regenerative medicine are occurring at a rapid pace. And OMICS technologies (e.g., genomics, proteomics, metabolomics, transcriptomics, glycomics, and lipomics), originally developed and used in the lab, are now making their way into clinical medicine, truly ready to usher in an era of personalized medicine.

The 2014 BIO International Convention will be held in San Diego this June. As usual, the BIO conference committee did a superb job in putting together a first-class program that covers a wide range of topics with something to offer everyone involved in biotech R&D or commercialization. Its been a tough call this year but here are my picks for the top 10 cant miss sessions at the conference.

To learn more about the program and available registration packages for Convention, please visithere

John Sterling is editor-in-chief of Genetic Engineering & Biotechnology News (GEN).

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GENs Top 10 Session Picks for the 2014 BIO International Convention

Today virtually everything we eat is produced from seeds that have been genetically altered in some way. New methods of plant tinkering have emerged over the generations and so, too, have the fears

Today virtually everything we eat is produced from seeds that have been genetically altered in one way or another. Credit: Thinkstock

Editor's note: The following is the introduction to the May 2014 issue of Scientific American Classics: The Birth of the Great GMO Debate.

The idea of intentionally infecting a plant with a bacterium might seem strange. Just three decades ago, however, researchers discovered that they could use this infection to deliver new and potentially useful genes into crops.

What has long appeared to be simply the agent of a bothersome plant disease is likely to become a major tool for the genetic manipulation of plants: for putting new genes into plants and thereby giving rise to new varieties with desired traits, announced acclaimed scientist Mary-Dell Chilton in 1983 in a pioneering article, one of many in this collection from the archives of Scientific American. Today genes introduced this way are yielding some of the most exciting new approaches to food securityas well as a hearty amount of debate.

Despite the excitement about the potential benefits of genetic engineering 30 years ago, the broader historical perspective highlighted in this collection reveals that this is just one of many thrilling and surprising advances in the long history of plant genetic alteration, which began well before this retrospective issue could document. (Scientific American extends back only to 1845.) Consider the assessment of the new technology of cross-pollination described in 1717 by botanist Richard Bradley: A curious person may by this knowledge produce such rare kinds of plants as have not yet been heard of.

For 10,000 years, in fact, we have altered the genetic makeup of our crops. For example, the ancient ancestor of modern corn was created some 6,000 years ago by Native Americans who domesticated a wild plant called teosinte, which looks nothing like a modern corn plant. If humans still depended on this wild relative, we would need hundreds, if not thousands, of times more plantsand acresto replace corn.

Today virtually everything we eat is produced from seeds that have been genetically altered in one way or another. The old approaches were crude and have been refined over the centuries. Modern methods include grafting and forced pollination (mixing genes of distantly related species) and radiation treatments to create random mutations in seeds. The newest method is genetic engineeringa technology developed after scientists observed that the bothersome plant pathogen Agrobacterium tumefaciens habitually introduced its own genes into plants. With a little laboratory work, the bacterium can instead implant desirable genes, such as those that increase nutrients or help the plant resist pests or drought.

The planting of genetically engineered crops during the past 20 years has drastically reduced the amount of synthetic insecticides sprayed worldwide, shifted the use of herbicides to those that are less toxic, rescued the U.S. papaya industry from disease, and benefited the health and well-being of farmers and their families and consumers. Every scientific review of the crops on the market so far has concluded that the plants are safe to eat.

Just as the excitement surrounding the benefits of genetic engineering paralleled those of our predecessors, so, too, has the fear of plant tinkering technologies persisted over time. Consider the comments of Maxwell T. Masters, president of the International Conference of Hybridization, in his 1899 Scientific American article: Many worthy people objected to the production of hybrids on the ground that it was an impious interference with the laws of Nature. Today we are all too familiar with similar arguments about the application of genetic engineering in agriculture.

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Plant Engineers Sow Debate

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An overview of Genetic Engineering 2
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Genetic engineering and transgenic organisms

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PUBLIC RELEASE DATE:

30-Apr-2014

Contact: Vicki Cohn vcohn@liebertpub.com 914-740-2100 x2156 Mary Ann Liebert, Inc./Genetic Engineering News

New Rochelle, NY, April 30, 2014James M. Wilson, MD, PhD (University of Pennsylvania Perelman School of Medicine, Philadelphia) has dedicated his research and medical career to developing gene therapy and the vectors needed to deliver genes into cells for the treatment and cure of inherited diseases. In recognition of his leadership and accomplishments, Dr. Wilson has received a Pioneer Award, bestowed by a blue ribbon panel*, from Human Gene Therapy, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers. Human Gene Therapy is commemorating its 25th anniversary by honoring the leading 12 Pioneers in the field of cell and gene therapy and publishing a Pioneer Perspective by each of the award recipients. The Perspective by Dr. Wilson is available on the Human Gene Therapy website.

In his essay "Genetic Diseases, Immunology, Viruses, and Gene Therapy," Dr. Wilson traces the path, motivating factors, and mentors and colleagues that led him from his early work identifying the mutations responsible for the devastating childhood disease Lesch-Nyhan syndrome (LNS) to the exploration of novel techniques and molecular tools for transferring therapeutic genes first into animals and then into humans. Since joining the faculty at the University of Pennsylvania more than 20 years ago, much of his research has focused on the development of adenoviral and adeno-associated viral vectors as vehicles for gene delivery.

Noting that the commercialization of gene therapy is still in its infancy, Dr. Wilson states that "We are entering a remarkable era of gene therapy research that will accelerate its development and lead to a number of commercial products across a spectrum of diseases." His laboratory has made seminal contributions to the basic biology of vectors and the development of current generation vector technologies that have enabled others to successfully move into the clinic.

"Dr. Wilson strongly deserves this accolade as an HGT pioneer of gene and cell therapy," says Deputy Editor George Dickson, BSc, PhD, University of London, Surrey. "His unparalleled contributions to the adenoviral and AAV vector fields over more than 25 years have been profound and seminal. Vectors from Dr. Wilson's lab at the University of Pennsylvania have been distributed around the globe, and are bearing fruit in viral vaccine and viral gene therapy areas spanning a plethora of disease targets."

###

*The blue ribbon panel of leaders in cell and gene therapy, led by Chair Mary Collins, PhD, MRC Centre for Medical Molecular Virology, University College London selected the Pioneer Award recipients. The Award Selection Committee selected scientists that had devoted much of their careers to cell and gene therapy research and had made a seminal contribution to the field--defined as a basic science or clinical advance that greatly influenced progress in translational research.

About the Journal

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James Wilson, M.D., Ph.D. receives Pioneer Award