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Category Archives: Human Genetic Engineering

J. Craig Venter describes biofuels, vaccines and foods from made-to-order microbes

In a plenary talk titled, "From Reading to Writing the Genetic Code," Venter described a fundamental shift in his field of genomics, and its promise for producing synthetic life that could help provide 21st century society with new fuels, medicines, food and nutritional products, supplies of clean water and other resources. Venter, a pioneer in the field, led the team at Celera Genomics that went head-to-head with the government-and-foundation-funded Human Genome Project in the race to decode the human genome. This quest, in which the 23,000 human genes were deciphered, ended with the teams declaring a tie and publishing simultaneous publications in 2001.

"Genomics is a rapidly evolving field and my teams have been leading the way from reading the genetic code deciphering the sequences of genes in microbes, humans, plants and other organisms to writing code and constructing synthetic cells for a variety of uses. We can now construct fully synthetic bacterial cells that have the potential to more efficiently and economically produce vaccines, pharmaceuticals, biofuels, food and other products."

The work Venter described at the ACS session falls within an ambitious new field known as synthetic biology, which draws heavily on chemistry, metabolic engineering, genomics and other traditional scientific disciplines. Synthetic biology emerged from genetic engineering, the now-routine practice of inserting one or two new genes into a crop plant or bacterium. The genes can make tomatoes, for instance, ripen without softening or goad bacteria to produce human insulin for treating diabetes. Synthetic biology, however, involves rearranging genes on a much broader scale that of a genome, which is an organism's entire genetic code to reprogram entire organisms and even design new organisms.

Venter and his team at the not-for-profit J. Craig Venter Institute (JCVI), which has facilities in Rockville, Maryland, and San Diego, announced in 2010 that they had constructed the world's first completely synthetic bacterial cell. Using computer-designed genes made on synthesizer machines from four bottles of chemicals, the scientists arranged those genes into a package, a synthetic chromosome. When inserted into a bacterial cell, the chromosome booted up the cell and was capable of dividing and reproducing.

In the ACS talk, Venter described progress on major projects, including developing new synthetic cells and engineering genomes to produce biofuels, vaccines, clean water, food and other products. That work is ongoing at both JCVI and at his company, Synthetic Genomics Inc. (SGI). A project at SGI for instance, aims to engineer algae cells to capture carbon dioxide and use it as a raw material for producing new fuels. Another group uses synthetic genomic advances with the goal of making influenza vaccines in hours rather than months to better respond to sudden mutations in those viruses.

Venter also described his work in sequencing the first draft human genome in 2001 while he and his team were at Celera Genomics, as well as the work on his complete diploid genome published in 2007 by scientists at JCVI, along with collaborators at The Hospital for Sick Children in Toronto and the University of California, San Diego. In addition to continued analysis of Venter's genome, he and his team are also studying the human microbiome, the billions of bacteria that live in and on people, and how these microbes impact health and disease.

While technology is rapidly changing, making human genome sequencing more and more accessible, the accuracy of these next generation machines remain a challenge. Thus, Venter believes it may be years before such full-genome sequences become accurate enough to find a place in routine medical care.

Provided by American Chemical Society (news : web)

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Genetics of flu susceptibility

Public release date: 25-Mar-2012 [ | E-mail | Share ]

Contact: Aileen Sheehy as22@sanger.ac.uk 44-122-349-2368 Wellcome Trust Sanger Institute

A genetic finding could help explain why influenza becomes a life-threating disease to some people while it has only mild effects in others. New research led by the Wellcome Trust Sanger Institute has identified for the first time a human gene that influences how we respond to influenza infection.

People who carry a particular variant of a gene called IFITM3 are significantly more likely to be hospitalised when they fall ill with influenza than those who carry other variants, the team found. This gene plays a critical role in protecting the body against infection with influenza and a rare version of it appears to make people more susceptible to severe forms of the disease. The results are published in the journal Nature.

A central question about viruses is why some people suffer badly from an infection and others do not. IFITM3 is an important protein that protects cells against virus infection and is thought to play a critical role in the immune system's response against such viruses as H1N1 pandemic influenza, commonly known as 'swine flu'. When the protein is present in large quantities, the spread of the virus in lungs is hindered, but if the protein is defective or absent, the virus can spread more easily, causing severe disease.

"Although this protein is extremely important in limiting the spread of viruses in cells, little is known about how it works in lungs," explains Aaron Everitt, first author from the Wellcome Trust Sanger Institute. "Our research plays a fundamental part in explaining how both the gene and protein are linked to viral susceptibility."

The antiviral role of IFITM3 in humans was first suggested by studies using a genetic screen, which showed that the protein blocked the growth of influenza virus and dengue virus in cells. This led the team to ask whether IFITM3 protected mice from viral infections. They removed the IFITM3 gene in mice and found that once they contracted influenza, the symptoms became much more severe compared to mice with IFITM3. In effect, they found the loss of this single gene in mice can turn a mild case of influenza into a fatal infection.

The researchers then sequenced the IFITM3 genes of 53 patients hospitalised with influenza and found that some have a genetic mutant form of IFITM3, which is rare in normal people. This variant gene encodes a shortened version of the protein which makes cells more susceptible to viral infection.

"Since IFITM3 appears to be a first line defender against infection, our efforts suggest that individuals and populations with less IFITM3 activity may be at increased risk during a pandemic and that IFITM3 could be vital for defending human populations against other viruses such as avian influenza virus and dengue virus" says Dr. Abraham Brass, co-senior author and Assistant Professor at the Ragon Institute and Gastrointestinal Unit of Massachusetts General Hospital.

This research was a collaboration between institutes in the United States and the United Kingdom. The samples for this study were obtained from the MOSAIC consortium in England and Scotland, co-ordinated from the Centre for Respiratory Infection (CRI) at Imperial College London, and the GenISIS consortium in Scotland at the Roslin Institute of the University of Edinburgh. These were pivotal for the human genetics component of the work.

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J. Craig Venter, Ph.D., describes biofuels, vaccines and foods from made-to-order microbes

Public release date: 25-Mar-2012 [ | E-mail | Share ]

Contact: Michael Bernstein m_bernstein@acs.org 619-525-6268 (March 23-28, San Diego Press Center) 202-872-6042

Michael Woods m_woods@acs.org 619-525-6268 (March 23-28, San Diego Press Center) 202-872-6293 American Chemical Society

SAN DIEGO, March 25, 2012 Just as aspiring authors often read hundreds of books before starting their own, scientists are using decades of knowledge garnered from sequencing or "reading" the genetic codes of thousands of living things to now start writing new volumes in the library of life. J. Craig Venter, Ph.D., one of the most renowned of those scientists, described the construction of the first synthetic cell and many new applications of this work today at the 243rd National Meeting & Exposition of the American Chemical Society (ACS), the world's largest scientific society, which is underway this week.

In a plenary talk titled, "From Reading to Writing the Genetic Code," Venter described a fundamental shift in his field of genomics, and its promise for producing synthetic life that could help provide 21st century society with new fuels, medicines, food and nutritional products, supplies of clean water and other resources. Venter, a pioneer in the field, led the team at Celera Genomics that went head-to-head with the government-and-foundation-funded Human Genome Project in the race to decode the human genome. This quest, in which the 23,000 human genes were deciphered, ended with the teams declaring a tie and publishing simultaneous publications in 2001.

"Genomics is a rapidly evolving field and my teams have been leading the way from reading the genetic code deciphering the sequences of genes in microbes, humans, plants and other organisms to writing code and constructing synthetic cells for a variety of uses. We can now construct fully synthetic bacterial cells that have the potential to more efficiently and economically produce vaccines, pharmaceuticals, biofuels, food and other products."

The work Venter described at the ACS session falls within an ambitious new field known as synthetic biology, which draws heavily on chemistry, metabolic engineering, genomics and other traditional scientific disciplines. Synthetic biology emerged from genetic engineering, the now-routine practice of inserting one or two new genes into a crop plant or bacterium. The genes can make tomatoes, for instance, ripen without softening or goad bacteria to produce human insulin for treating diabetes. Synthetic biology, however, involves rearranging genes on a much broader scale that of a genome, which is an organism's entire genetic code to reprogram entire organisms and even design new organisms.

Venter and his team at the not-for-profit J. Craig Venter Institute (JCVI), which has facilities in Rockville, Maryland, and San Diego, announced in 2010 that they had constructed the world's first completely synthetic bacterial cell. Using computer-designed genes made on synthesizer machines from four bottles of chemicals, the scientists arranged those genes into a package, a synthetic chromosome. When inserted into a bacterial cell, the chromosome booted up the cell and was capable of dividing and reproducing.

In the ACS talk, Venter described progress on major projects, including developing new synthetic cells and engineering genomes to produce biofuels, vaccines, clean water, food and other products. That work is ongoing at both JCVI and at his company, Synthetic Genomics Inc. (SGI). A project at SGI for instance, aims to engineer algae cells to capture carbon dioxide and use it as a raw material for producing new fuels. Another group uses synthetic genomic advances with the goal of making influenza vaccines in hours rather than months to better respond to sudden mutations in those viruses.

Venter also described his work in sequencing the first draft human genome in 2001 while he and his team were at Celera Genomics, as well as the work on his complete diploid genome published in 2007 by scientists at JCVI, along with collaborators at The Hospital for Sick Children in Toronto and the University of California, San Diego. In addition to continued analysis of Venter's genome, he and his team are also studying the human microbiome, the billions of bacteria that live in and on people, and how these microbes impact health and disease.

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J. Craig Venter, Ph.D., describes biofuels, vaccines and foods from made-to-order microbes

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Reality check on 'Hunger Games' tech

Murray Close / Lionsgate / Everett Collection

Peacekeepers escort Katniss Everdeen (Jennifer Lawrence) in a scene from "The Hunger Games."

By Alan Boyle

The technological divide between the rulers and the ruled is at the heart of "The Hunger Games": While the good guys struggle to survive, the bad guys employ fictional gee-whiz technologies inspired by real-life frontiers. And just as in real life, technology gets tripped up by unintended consequences.

That's not to say the post-apocalyptic North America of the book series and the much-anticipated movie, opening Friday, is anything close to real life. On one level, the technologies used by the villainous government of the nation known as Panem, ranging from force fields to extreme genetic engineering, serve as science-fiction plot devices and special effects. But on another level, the contrast between bows and arrows on one side, and death-dealing hovercraft on the other, accentuates the saga's David vs. Goliath angle or, in this case, Katniss vs. the Capitol.

Here are a few of the technological trends that provide the twists in "The Hunger Games," along with real-world analogs:

What? No cellphones? Much has been made of the fact that the starving, downtrodden residents of Panem's districts don't seem to have access to cellphones or the Internet. Instead, they have to huddle around giant television sets to find out what their overlords in the Capitol want them to see. But if you think of Panem as a fictional tweak of modern-day North Korea, "The Hunger Games" might not be that far off the mark: You've got a leadership capable of long-range missile launches, exercising virtually total control over what its impoverished populace sees and hears. Cellphones were outlawed until 2008, and even today they're confiscated from international visitors upon arrival. Internet access and international calling are limited to the elite.

The outlook for change is mixed: Today, a million North Koreans are said to be using mobile phones, but the State Department's Alec Ross told the Korea Times during a recent visit to Seoul that "it will be very difficult for technology to drive change in North Korea, given the extreme measures that North Korea has taken to create a media blackout." That's life in Panem ... er, Pyongyang.

Genetic engineering The most vivid special effects are connected to genetic engineering of various organisms, including humanized animals. To minimize the plot-spoiler effect, the only "muttation" I'll mention in detail is the mockingjay, which figures so prominently in the advance publicity and provides the title for the third book in Suzanne Collins' "Hunger Games" trilogy. The geniuses at the Panem high command created genetically modified birds known as jabberjays that were able to listen in on rebel conversations and report them back to the authorities. When the rebels caught onto this, they started feeding the jays false information. And when the Capitol figured this out, they left the jabberjays to fend for themselves. Male jabberjays mated with female mockingbirds, resulting in birds that could learn and repeat musical notes but not human speech.

The twist illustrates a time-honored movie maxim about genetic engineering, enunciated in the first "Jurassic Park" film: "Life will not be contained." That may be putting it too simply, but the field has certainly raised a lot of questions about how to keep genetic genies in the bottle. This month, more than 100 groups issued a call to hold back on synthetic biology until new guidelines are drawn up.

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Spotlight on Synthetic Biology

In a guest post at Scientific American's Lab Rat blog, iGEM-UANL team member Miguel Angel Loera Snchez discusses what he calls the "mainstream fronts of synthetic biology." These five fronts DNA synthesis, biological parts standardization, genetic code expansion, synthetic genetic circuits, and metabolic engineering have helped synthetic biology become "a fast growing and productive field," Snchez says. While much work remains to be done, the field "is attracting many smart and active young minds from different disciplines," he adds, leading him to believe that "the growth and innovation rate will likely increase in the years to come."

Meanwhile, the Woodrow Wilson International Center for Scholars's Synthetic Biology Project seeks to assess the societal impacts of advances in the field through a new public survey. The survey asks participants a variety of questions to investigate the ethical, legal, and social implications of synthetic biology research. "The results of this anonymous survey will be analyzed and compiled into a report, which will be released in mid- to late-May 2012," the Synthetic Biology Project group notes.

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Researchers building melanoma vaccine to combat skin cancer

ScienceDaily (Mar. 19, 2012) Mayo Clinic researchers have trained mouse immune systems to eradicate skin cancer from within, using a genetic combination of human DNA from melanoma cells and a cousin of the rabies virus. The strategy, called cancer immunotherapy, uses a genetically engineered version of the vesicular stomatitis virus to deliver a broad spectrum of genes derived from melanoma cancer cells directly into tumors. In early studies, 60 percent of tumor-burdened mice were cured in fewer than three months and with minimal side effects.

Results of the latest study appear this week in the journal Nature Biotechnology.

"We believe that this new technique will help us to identify a whole new set of genes that encode antigens that are important in stimulating the immune system to reject cancer. In particular, we have seen that several proteins need to be expressed together to generate the most effective rejection of the tumors in mice," says Richard Vile, Ph.D., a Mayo Clinic researcher in the Department of Molecular Medicine and a coauthor of the study, along with Jose Pulido, M.D., a Mayo Clinic ophthalmologist and ocular oncologist.

Dr. Vile's success with melanoma adds to Mayo Clinic's growing portfolio of experimental cancer vaccines, which includes an active clinical trial of vesicular stomatitis vaccines for liver cancers. Future studies could include similar vaccines for more aggressive cancers, such as lung, brain and pancreatic.

"I do believe we can create vaccines that will knock them off one by one," Dr. Vile says. "By vaccinating against multiple proteins at once, we hope that we will be able to treat both the primary tumor and also protect against recurrence."

The immune system functions on a seek-and-destroy platform and has fine-tuned its capacity to identify viral invaders such as vesicular stomatitis virus. Part of the appeal of building cancer vaccines from the whole spectrum of tumor DNA is that tumors can adapt to the repeated attacks of a healthy immune system and display fewer antigens (or signposts) that the immune system can identify.

Cancers can learn to hide from a normal immune system, but appear unable to escape an immune system trained by the vesicular stomatitis virus with the wide range of DNA used in the library approach.

"Nobody knows how many antigens the immune system can really see on tumor cells," says Dr. Vile. "By expressing all of these proteins in highly immunogenic viruses, we increased their visibility to the immune system. The immune system now thinks it is being invaded by the viruses, which are expressing cancer-related antigens that should be eliminated."

Much immunotherapy research has slowed because of researchers' inability to isolate a sufficiently diverse collection of antigens in tumor cells. Tumors in these scenarios are able to mutate and reestablish themselves in spite of the body's immune system.

The study was a Mayo collaboration with professors Alan Melcher and Peter Selby at the Leeds Institute of Molecular Medicine, University of Leeds, U.K. They were also co-authors.

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Researchers building melanoma vaccine to combat skin cancer

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