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Posts Tagged ‘synthetic biology

Science Policy Around the Web – April 7, 2017

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By: Kseniya Golovnina, PhD

Cancer Research

RNA-Seq Technology for Oncotargets Discovery

One of the most significant discoveries in cancer research, using the “Big Data” approach with experimental validations, was made recently by Chinese and American scientists together with They described the first cancer predisposition, familially-inherited, fusion gene, KANSARL, specific to populations with European ancestry, by using advanced RNA-sequencing (RNA-seq) of cancer transcriptomes.

A fusion gene is a hybrid formed from two previously separate genes as a result of chromosomal rearrangements. Often, fusion genes are oncogenes. The first fusion gene abnormality was described in a human malignancy and was called the Philadelphia chromosome. In the early 1980s, scientists showed that a translocation between chromosomes 9 and 22 led to the formation of a fusion gene (BCR/ABL1), which produced a chimeric protein with the capacity to induce chronic myeloid leukemia. KANSARL is the most prevalent cancer gene discovered so far. Scientists systematically analyzed the RNA-seq data of many cancer types from different parts of the world, together with RNA-seq datasets of the 1000 Genome Project. KANSARL fusion transcripts were rarely detected in tumor samples of patients from Asia or Africa, but occurred specifically in 28.9% of the population of European origin.

Scientists from Cancer Genome Anatomy project at the National Cancer Institute (NCI), using sophisticated sequencing techniques, have identified 10,676 gene fusions among cancer-related chromosomal aberrations. has identified over 1.1 million novel fusion transcripts, many of which are likely biomarkers of diseases. Fusion genes play an important role in diagnosis and monitoring of cancer treatment progress by measuring the disappearance of the fusion and, thereby, the disappearance of the tumor tissue. Currently, several clinical trials are aimed at treating fusion-positive patients with a range of targeted therapies, which will hopefully lead to novel therapy development and save patients’ lives. (Splicingcodes)


Turning Mammalian Cells into Biocomputers to Treat Human Disease

Engineering cells by manipulating DNA and controlling their performance is a growing field of synthetic biology. Scientists have been working with bacterial cells for years to perform different controlled actions, for example, lighting up when oxygen levels drops. Bacterial cells, including Escherichia coli, have a simple genome structure and are relatively easy to manipulate. Using bacterial cells, it was possible also to join several genetic circuits within a single cell to carry out more complex actions.

After successful engineering in bacteria, researchers have aimed to create genetic circuitry to detect and treat human disease in mammalian cells. Most of the attempts have failed due to the complexity of the mammalian genome, until a group of biomedical engineers from Boston and Basel, Switzerland decided to upgrade their DNA “switches”. They used an ability of special enzymes, DNA recombinases, to selectively cut and stitch DNA. The new system in mammalian cells is called ‘Boolean logic and arithmetic through DNA excision’ (BLADE). BLADE founders built a wide variety of circuits (113), each designed to carry out a different logical operation with 96.5% success. This Boolean system has great potential for applications in cell and tissue engineering. One exciting possibility is engineering T-cells with genetic circuits that initiate a suicide response to kill tumors when they detect the presence of two or three “biomarkers” produced by cancer cells. (Robert F. Service, ScienceNews)

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April 7, 2017 at 9:22 am

Synthetic Biology to Cure Diseases – Promises and Challenges

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By: Emmette Hutchinson, PhD

       Synthetic biology is an interdisciplinary field that utilizes an engineering approach to construct novel biological products, circuits and designer organisms. This field has the potential to revolutionize many aspects of society from chemical production to healthcare. Synthetic biology holds particular promise in the production of biological therapeutics or chemical compounds for the treatment of disease. Increased efficiency and stability of production can be especially beneficial when treating global diseases that are typically associated with poverty. Treatment for these conditions is typically funded by grants from large charitable foundations, sometimes leading to scarcity as funding recedes.

In 2015, 212 million cases of malaria were reported worldwide, predominantly among the poorest countries in the world. While major initiatives such as the President’s Malaria initiative and the Gates foundation focus on various aspects of combating the disease, such as the spread of the parasite and the eradication of the disease, respectively, cost-effective treatments for infections are still needed. The most efficacious treatments for malaria are artemisinin-based combination therapies (ACTs). The 2015 Nobel Prize in Medicine was awarded in part to Youyou Tu for her work demonstrating that artemisinin, an Artemisia annua (sweet wormwood) extract, was an effective anti-malarial treatment. Landmark research published in 2006 demonstrated synthetic production of artemisinic acid, a precursor to artemisin, in yeast. Prior to this study, the only source of artemisinin was tiny hairs found on the surface of the wormwood. The supply of artemisinin has previously been unstable, resulting in dramatic price fluctuations. These price spikes have resulted in both shortages and unattainable cost of treatment. The pharmaceutical giant Sanofi licensed the yeast strain with the hope of creating a more reliable source of artemisinin. In part, due to market forces pushing down the price of artemisinin (primarily a surge in world-wide Artemisia annua cultivation), Sanofi recently sold both its technology and production facilities to Huvepharma. Despite the potential of synthetic biology to disrupt the pharmaceutical industry, this is an example of how existing production methods can impede adoption of more efficient (and stable) synthetic approaches. An alternative to synthetic production of artemisinin in yeast, termed COSTREL (combinatorial supertransformation of transplastomic recipient lines), re-creates the enzymatic pathway necessary to produce artemisinin in tobacco. Although not as efficient as synthetic production of the chemical in yeast, this route offers a significant per-acre boost in artemisinin production over the native source and a potentially more open market to supply drug manufacturers.

Similar to malaria, snake bites predominantly affect impoverished regions of the world. This makes the use of life-saving anti-venoms particularly burdensome as they are both expensive and difficult to produce. The World Health Organization estimates that up to 2.5 million cases of envenoming occur each year, resulting in death, amputations and permanent disabilities. Antivenoms are typically produced using plasma from hyperimmune animals, an often expensive and time-consuming process. In some cases, the profit margins are considered too low to continue producing effective antivenoms such as FAV-Afrique, a polyvalent antivenom effective against 10 species of sub-Saharan snakes. Two recent approaches utilizing synthetic antibody fragments have shown promising effects for protection against specific snake venoms. In a screen for antibody fragments to snake venom, Prado and colleagues found two fragments that protected mice against muscle damage from Bothrops jararacussu and Bothrops brazili venom. Ramos and colleagues designed two synthetic DNA sequences encoding components of coral snake (Micrurus corallinus) venom. Serum obtained from animals immunized with these DNA sequences resulted in 60% survival of animals given a lethal dose of coral snake venom. This second approach eliminates the need for difficult-to-obtain venom when seeking to generate hyperimmune animals as anti-venom producers. It is possible that these or similar synthetic biology approaches could be utilized to produce FAV-Afrique or other polyvalent antivenoms in a faster, more cost-effective manner than hyperimmune animals.

While the possibility of artemisinic acid-producing yeast, high artemisinin-yielding tobacco, and more efficient sources of anti-venom are compelling, regulatory challenges and ethical dilemmas are abundant in the burgeoning field of synthetic biology. Both the US and the EU have recently held surveys and drafted opinions concerning the ethics and risks of synthetic biology. One potential issue with the use of synthetic biology approaches to industrial scale production of chemicals or recombinant proteins is the potential for uncontained spread of the recombinant organism or uncontrolled transfer of the modified genetic material. Another concern centers around the impact of synthetic biology on existing biological diversity. There are also concerns regarding the proliferation of synthetic biology capabilities and biosecurity. At the moment, the United States is in middle of an epidemic of opioid addiction. Synthesis of more complex chemicals in yeast also opens up issues with substance control. A research group has already demonstrated the ability to synthesize heroin in yeast, cheaply and effectively in much the same manner as one might brew beer, raising the possibility that new, designer substances of abuse could be produced in a similar manner. Approaches to the issue of biocontainment have varied, but as the control of synthetic transcriptional circuits becomes robust, more efficacious approaches to biocontainment can be developed. One recent approach to this problem implemented a two-part genetic version of a Dead Man’s Switch into E. coli, which will kill the synthetic organism when certain conditions are not met. As a standard operating procedure, this system would go a long way toward addressing containment of engineered organisms.

The engineering of novel biologicals, re-purposing of existing or development of new transcriptional circuits and entirely new organisms holds immense promise for all aspects of society. These technologies will likely impact the treatment of diseases typically associated with poverty initially, as the increased efficiency of production will lead to stability in price and decreased scarcity of therapeutics. Once concerns of containment and potential effects on existing ecosystems are sufficiently addressed, the broad application of these technologies becomes more reasonable. As the methodologies enabling the creation of designer organisms and novel biologicals improves, the market forces that impede adoption of more efficient synthetic sources of therapeutics may also have less of an impact.

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February 23, 2017 at 4:33 pm

Science Policy Around the Web – May 17, 2016

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By: Melissa Pegues, Ph.D.

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Zika Virus

WHO’s Zika guidelines don’t include delaying Olympics

With the summer Olympic games slated to begin in Brazil in August, many have expressed concerns about the health risks posed by the recent outbreak of Zika virus in Central and South America. Despite these concerns, the World Health Organization (WHO) released a statement on Thursday making it clear that they are not calling for a cancellation of the Olympic games this summer.

The Zika virus, which is transmitted by mosquitoes, has garnered much attention recently after infection with the virus during pregnancy has been found to cause microcephaly in infants. Microcephaly is a birth defect in which the brain does not develop properly resulting in a smaller than normal head. The virus has also been associated with the development of Guillian-Barre syndrome, a rare form of paralysis.

Although many prominent medical ethicists have publicly called for the postponement or relocation of the games, few athletes have expressed concern over the risks posed by Zika. However, Marcos Espinal, the director of the Zika response of the Pan American Health Organization, has strongly rejected the idea of postponing the games. He cited trends seen from dengue and chikungunya, similar viruses that are also carried by the same Aedes aegypti mosquito, in that infections peak during the summer months and subsequently drop off after the season changes. Furthermore, he noted that the games are occurring in the winter months of August and September when mosquitoes are not so abundant. International Olympic Committee (IOC) director, Richard Budgett, reaffirmed that although the situation is being closely monitored, the IOC is committed to continuing with the Olympic games this summer.

In their statement, WHO urged athletes and anyone traveling to Brazil to attend the Olympic games to take steps to protect against Zika, including wearing insect repellent and clothing that covers as much of the body as possible. The WHO statement also cautions against sexual transmission of the virus and suggested practicing safe sex or abstaining from sex during their stay and for at least four weeks after returning from the epidemic zone. This recommendation contrasts those issued by the Centers for Disease Control (CDC) that recommend abstaining from sex for eight weeks after returning, further highlighting how little is known about transmission of the virus. There have been few documented cases of sexual transmission and many questions regarding sexual transmission of the virus remain, including if an asymptomatic infected person can transmit the virus sexually. WHO also recommended that Olympic visitors stay in air-conditioned accommodations and avoid areas where there is increased risk of being bitten by a mosquito such as “impoverished and overcrowded areas in cities and towns with no piped water and poor sanitation.” (Pam Belluck, New York Times)

Genetic Engineering

Secret Harvard meeting on synthetic human genomes incites ethics debate

The ability to modify the genome is rapidly advancing the medical field, but a private meeting of scientists has brought intrigue and concern to the field of genetics. Nearly 150 Scientists gathered at Harvard Medical School last week to discuss how to create a complete genome from scratch. The project has been described as a follow-up to the human genome project, but rather than aiming to read all of the base pairs of the human genome, the goal is to synthesize a “complete human genome.” Although scientists already have the capability to synthesize DNA chemically, significant focus is being given to improving these techniques with the goal to construct complete genomes that could be implanted in cells for research purposes.

However, the meeting has drawn criticism because the organizers of the event asked attendees not to contact the media or post to Twitter during the meeting. Researchers Drew Endy and Laurie Zoloth published an essay questioning the decision to keep the meeting private. In their joint statement they questioned whether the organizers gave full consideration to potential ethical issues by asking “how many Einstein genomes should be made and installed in cells, and who would get to make them?”

George Church, the Harvard geneticist who oversaw the meeting, explained that the project was aimed at creating cells, not people. He further explained that the project is not restricted to the human genome, and that these techniques could be applied to other animals, plants, and microbes. The meeting was originally intended to be open with video streaming and numerous invited journalists, but attendees were asked not to publicly discuss the event since there were also plans to pair the meeting with a peer-reviewed article. Church commented that “there was nothing secret about it” that a video of the meeting will be released with their soon-to-be published peer-reviewed article. (Joel Achenbach, Washington Post)

Federal Science Initiatives

Earth’s microbes get their own White House Initiative

With months left in Obama’s presidency, the White House Office of Science and Technology has announced yet another scientific endeavor, the National Microbiome Initiative (NMI). This latest initiative will join numerous other efforts in the Obama administration’s scientific legacy including: the BRAIN Initiative, the Antibiotic Resistance Solutions Initiative, the Precision Medicine Initiative (PMI), and the Cancer Moonshot Initiative. The human “microbiome” is the collection of microbes that inhabit our bodies, and variations in its composition has been found to correlate with many diseases including autoimmune diseases, diabetes, and obesity.

The NMI however includes many governmental departments to study the microbiome of many ecosystems such as “those that help plants pull nutrients from soil, to those that capture and release carbon dioxide in the ocean.” Because these environments contain many species of bacteria, viruses, and fungi, determining the role of any one species is nearly impossible. Reaching the lofty goals set by this initiative will require better tools to dissect individual species within the microbiome, and to address these shortcomings, the NMI has set forth 3 goals:  supporting interdisciplinary research, developing platform technologies, and expanding the microbiome workforce. To support these goals, the NMI will receive an investment of $121 million dollars from federal 2016 fiscal appropriations and 2017 fiscal proposals, as well as commitments of $400 million dollars from stakeholder and institutions in different sectors. (Kelly Servick, ScienceInsider)

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May 17, 2016 at 9:00 am

Science Policy Around the Web – April 6, 2016

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By: Sterling Payne, B.Sc.

Artificial Intelligence

To Beat Go Champion, Google’s Program Needed a Human Army

“It may be a hundred years before a computer beats humans at Go — maybe even longer,” Dr. Piet Hut communicated to New York Times’ George Johnson in a 1997 conversation. The event prompting their discussion was the victory of IBM’s Deep Blue over grandmaster Garry Kasparov in a series of chess games. Dr. Hut’s prediction was bested by about 80 years by AlphaGo, the product of Google’s DeepMind. AlphaGo recently secured a victory against 9 dan Go champion Lee Sedol in a 5-game match hosted by Google. By nature, Go as a game is more complex than chess; less stringent gameplay guidelines don’t offer a surefire way to determine which player is at an advantage. Rather than powering through an analysis of thousands upon thousands of potential moves each turn, AlphaGo utilizes a novel combination of machine-learning methods to determine which board configurations are more advantageous, and positively reinforces correct decisions via thousands of matches played against itself. The product of this is an artificial intelligence (AI) that more closely represents human intuition, at least in the small scope of the Chinese board game.

With its 4-1 victory over Sedol, AlphaGo demonstrated extreme proficiency in the game of Go, but in only that. While inarguably an astounding accomplishment and significant leap in the field of computer science, AIs like AlphaGo have a long way to go before they can replicate the intuition of the human mind, which is far expandable beyond an ancient board game. In terms of policy, the very methods used to create AlphaGo could also find their ways into hospitals and healthcare facilities in the near future. With the advent of artificial intelligence in the workplace, extra considerations will have to be taken by patients and care providers alike in terms of personal information, data management, and general communication. (George Johnson, The New York Times) (Will Knight, MIT Technology Review)

Federal Cancer Research

Blue Ribbon Panel Announced to Help Guide Vice President Biden’s National Cancer Moonshot

The Cancer Moonshot Initiative , headed by Vice President Joe Biden, plans to put an end to the disease that has plagued millions of humans for hundreds of years. Armed with a $1 billion budget over the next five years, the initiative’s primary aim is to speed up cancer research such that a decade’s worth of discoveries can occur in half that time. Two of the main areas where such discoveries will fall are detection and treatment. A task force to handle financial matters and progression of the initiative was announced in February, and just yesterday (April 04, 2016), the National Cancer Institute unveiled their Blue Ribbon Panel, a special selection of various leaders in the fields of cancer research and patient advocacy, to direct efforts of the initiative to where they are likely to make the largest impact.

As a society, our knowledge of cancer has grown considerably since the turn of the century; Cancer is no longer thought of as a single disease that affects people, rather, it is the product of multiple genetic mutations and cellular microenvironments, painting a unique disease landscape for each person it affects. Members were chosen such that the panel represented multiple walks of science from immunology to bioinformatics, as well as cancer prevention and treatment. Already armed with capital and a team to guide finances and general progress, the Cancer Moonshot Initiative has taken another giant step forward with the addition of the Blue Ribbon Panel. The full member list of the Blue Ribbon Panel and the original announcement are linked here. (News Releases, National Institutes of Health)


Biology software promises easier way to program living cells

With computer programming, the programmer gives the computer a set of instructions in one (or more) of several different programming languages. These instructions include logical operations such as true-false statements (i.e. “if this is true, then do this”) and various loops (i.e. “while this is true, do this”). At the end of all of this, sits a program, executed by the computer to provide some sort of output, whether it be ordering a data set, turning on a light, or spinning a motor. Dr. Christopher Voigt and his lab at MIT have taken these principles and applied them to their new software Cello, a programming language capable of producing working circuits in living systems. Cello requires the user to input commands, such as a function they would like a given cell to perform and under what conditions it should perform said function. After the input is compiled, the end result is a DNA sequence or “circuit” that, when placed inside a cell, can fulfill the function(s) specified by the user. In a paper recently published in Science (April 01, 2016), Alec Nielsen and colleagues used cell to generate 60 different DNA circuits, 75% of which worked as expected the first time when introduced into Escherichia coli cells.

As synthetic biology continues to grow and gain popularity throughout the research world, it is of increasing importance to think about what policies and potential restrictions should be set in place. Engineering de novo biological systems and functions can be extremely powerful, yet, if left in the wrong hands, could have significant consequences as with any equally commensurate technique (e.g. CRISPR-Cas9). (Erika Check Hayden, Nature News)

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April 6, 2016 at 12:00 pm