Synthetic Biology (SynBio) is characterized by a bottom-up approach to designing biological systems for specific purposes (Endy, 2005). In 2014, the European Commission defined the field as “the application of science, technology and engineering to facilitate and accelerate the design, manufacture and modification of genetic materials in living organisms”. It is a young field, but is now a global endeavor with research and development programs in many countries around the world. The ability to rapidly engineer organisms in laboratories by combining molecular biology tools with engineering principles holds “vast potential for the bioeconomy, and could dramatically transform high-impact fields such as agriculture, manufacturing, energy generation, and medicine.” (USA National Bioeconomy Blueprint 2012).

SynBio is unique in its highly multidisciplinary nature and that by ‘making biology easier to engineer’ it also facilitates ‘the contribution to scientific innovation from people who are not considered as professional experts in the traditional sense’ (Zhang 2012) including students, citizens and entrepreneurs. In this unique context, how can we support pre-competitive activities in biotechnology? What infrastructure is critical to collaborative efforts? What are potential organizational models?

A highly successful example of organizational model to foster synthetic biology is the iGEM competition in which hundreds of student teams from around the world work on SynBio projects, gather at MIT to showcase their achievements and make their work freely available on an opensource database. A searchable map of the hundreds of projects that have been done by students around the world was recently published (www.synbioconsulting.com/igem-synthetic-biologymap/). Since 2004, iGEM has played a crucial role in the ‘‘‘social’’ engineering’ of the upcoming generation of young scientists. iGEM ‘is seen to have significantly promoted a global open-access culture’, and by integrating so-called ‘human practice’ work in all projects it ‘also facilitates global exchange and dissemination of concerns over biosafety, biosecurity, IPR, ethics and public engagement’. Many nations, including China and the UK see iGEM as a strategic move to promote domestic progress in the life sciences (Zhang 2012). Much has to be learnt from this incentive driven approach to fostering the growth of synbio which makes learning and contributing to innovation engaging and rewarding.

Distributed innovation through gamification has shown a lot of potential to improve bioliteracy and contribute to the development of synbio. In other life science fields, games such as Foldit and EteRNA have been highly successful in capitalizing collective intelligence to answer fundamental questions about protein and RNA folding respectively, while simultaneously educating the players. In both games, players have matched and outperformed state of the art algorithmically computed solutions (Cooper 2010; Lee 2014). This approach has yet to be adapted for synbio but could provide an incredible tool to foster bioliteracy and constructive dialogue between actors.

Synbio entrepreneurship is still in its infancy. An overview of the different small and medium companies involved in the field is provided in the following link (SynbioProject map: http://www.synbioproject.org/sbmap/). Beyond possible regulatory burdens, education and access to seed funding would foster synbio entrepreneurship greatly. Nowadays, graduate programs are still geared towards tenure track in academia and do not reflect the reality of the work place. Data published in the National Science Board’s 2014 Science and Engineering Indicators show that a mere 29% of newly graduated life science PhDs (2010 data) will find a full time faculty position in the US. It is high time to introduce entrepreneurship and management skills (amongst others) into graduate programs. Beyond training, access to specific seed funding to kickstart companies is essential. Startup incubators such as YCombinator and Indie.Bio have recently been bringing a lot of fresh air into the synbio startup ecosystem by providing both support and founding.

From distributed innovation to gamification, and from entrepreneurship to science education, new organizational models are bound to revolutionize synbio. A collaborative effort should be made to foster the responsible and efficient growth of the field. In this process, knowledge should be exchanged and co-created between actors, and attention should be paid to embedding this new knowledge to minimize the mismatches between science, technology and their applications or uses (Roelofsen 2011) — in order to efficiently sprout new green bioeconomies around the World.

Exempts from a white paper written for Synbio Leap: a competitive fellowship for emerging leaders in biotechnology.

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Researchers Generate Opiates from Genetically Modified Yeast

A team of synthetic biology researchers led by Christina Smolke at Stanford University engineered yeast to produce thebaine, an opiate precursor to morphine and other painkiller medications, from primary metabolism. The team also demonstrated that with further strain development the genetically modified yeast could make hydrocodone, a widely used painkiller currently made from thebaine recovered from poppy plants

Previously, synthetic biologists have generated products using only a small number of added genes from a small number of species. This team added 21 genes to make thebaine and 23 genes to make hydrocodone from a number of distinct species including three different poppy species, rat, Goldthread, and Pseudomonas bacterium. Although this seems like a significant advancement in drug development, the microbes will need to increase thebaine production 100,000 fold before pharmaceutical companies become interested in using the genetically modified yeast as producers of opiates for medications.

The team stopped short of adding all of the genes necessary to generate morphine because biopolicy makers fear that if a strain of yeast that makes morphine gets into the hands of illicit drug makers, they could use it to easily generate heroine. Policy makers may need to ensure that no strains are developed for the production of illicit drugs or that genes are added to prevent opiate generating genes from surviving outside of controlled laboratory settings. Read the full paper here!

Intrexon Acquires Oxitec for $160 Million

Intrexon’s recent stock price decline did not stop it from acquiring Oxitec, a British company that engineers genetically modified insects, for $160 million in total considerations. Oxitec engineers males of a number of target species whose progeny do not reach adulthood when they mate with wild-type females. Continual release of these GMOs can decrease population sizes of specific target insects that consume crops and cause diseases below harmful threshold without using traditional insecticides and their ecological consequences.

In their current pipeline, Oxitec has genetically modified diamondback moths, pink bollworms, medflies, mexflies and olive flies to prevent crop destruction and also mosquitos to prevent Dengue fever, Chikungunya, and Yellow fever. At this point, only the Aedes aegypti OX513A mosquito construct to control Dengue fever is at the commercial optimization phase of development. It has obtained regulatory approvals for import and contained testing in Brazil, Cayman Islands, France, India, Malaysia, Singapore, Thailand, USA and Vietnam. Open field trials have taken place in Grand Cayman and Malaysia, and are currently also underway in Brazil.

Xenotransplantation of Pig Organs in Primates is Becoming More Successful

Revivicor, a company focused on eventually xenotransplanting genetically modified porcine tissue into humans, reported that a xenotransplantation of a pig heart into a baboon was not rejected for 945 days and a kidney was not rejected for a record-breaking 136 days. The heart transplant was “heterotropic”.  It was not critical to the survival of the baboon because although the heart was connected to the baboon’s circulatory system and able to beat, the baboon’s own heart remained in place to sustain life. The heart only failed afterEd the baboon was taken off immunosuppressant medication. The xenotransplantation of the kidney, however, was considered the longest life-sustaining xenotransplantation between a pig and a primate.

The scientists at Revivicor knocked out the pig’s alpha 1,3 galactosyltransferase gene, preventing the placement of galactose on branched sugar chains on cell surfaces that primate immune systems recognize and reject as part of the Hyperacute Rejection response. They also inserted five human genes into the transplanted organs. They inserted CD46, a cell surface protein that helps prevent the immune system from attacking host tissue, and a human version of thrombomodulin, a molecule that prevents clotting in blood vessels.

While these results seem very promising for xenotransplantation, pig to human transplants are still more than a few years away. Organs that are not rejected have not yet been developed because as one rejection problem is solved, another one presents itself. Revivicor is continuing their preclinical trials in primates and eventually intends to start clinical trials in humans if the results are promising. The first human xenotransplants will be used to sustain life while awaiting a human donor.

Editas Raises $120 Million in Series B Funding from 14 Investors, Including Bill Gates

Editas, a genome editing company with specific expertise in CRISPR/Cas 9 and TALENs technologies received $120 Million in Series B funding on August 10th, 2015. Boris Nikolic, M.D., Bill Gates’ former chief advisor for science and technology, founded bng0; a U.S. based Investment Company with the financial backing of Bill Gates with the specific purpose of funding Editas. As part of the funding agreement, Nikolic is joining the Board of Directors at Editas. In addition to bng0, a team of thirteen “cross-over” investors took part in the Series B funding.

The funding should keep the company afloat for the next three years, allowing it to advance multiple new therapies into clinical trials. Editas is concerned with gene therapy and the delivery of CRISPR/Cas9 proteins into the cells of sick patients using vectors. Editas’ first product likely to be tested in humans is their treatment of Leber’s congenital amaurosis type 10, a genetic disease that causes blindness. This is a good candidate for Editas’ delivery system because it is easy to deliver a vector to the eye and the condition is caused by a single substitution mutation that can be deleted. Editas is also working on curing sickle-cell anemia.

Editas also signed a deal with Juno Therapeutics in May 2015 to develop chimeric antigen receptor (CAR T) and high affinity T-cell receptor (TCR) therapies to treat blood borne cancers and solid tumors. Editas and Juno will edit a patient’s own T-cells to better recognize and destroy cancer cells. As part of that agreement, Juno paid Editas $25 million upfront and will pay them an extra $22 million in research support over the next five years. Editas will also be eligible for royalties and milestone payments upwards of $230 million for each of three separate programs.

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Oragenics and Intrexon’s Lantibiotic Platform Shows Promising Results 

Oragenics, a company focusing on the development of antibiotics against infectious disease and probiotics for oral health in humans and animals and Intrexon, a company which has been focusing on building a synthetic biology platform to create biologically based products have been collaborating to generate lantibiotics. Lantibiotics are a new class of peptide antibiotics that are effective in the treatment of antibiotic-resistant bacteria. On July 28, 2015, the companies released positive data in a critical animal study for multiple compounds from Oragenics’ Mutacin 1140 lantibiotic platform.  The compounds were subjected to a standard proof of concept animal model test to determine their efficacy against a clinically relevant C. difficile infection compared to a standard dose of vancomycin. The new drug candidate achieved a 100% animal survival rate in the trial, while vancomycin only achieved a 33% survival rate and the placebo control had a 0% survival rate.

The results of the trials helped Intrexon’s market cap exceed $6 billion and shares to reach an all time high of greater than $60. Investment analysts at Wunderlich last week valued Intrexon at $70 per share. Investors have high hopes for Intrexon as they now have a solid revenue stream due to their cattle-breeding platform and have various products that are in the works to reach the commercial market.

Soylent Hopes to Grow Food Replacement with Algae

During a failed startup attempt to create inexpensive cellphone towers in 2012, Rob Rhinehart realized that the food he was eating was not only “too expensive” but “nutritionally inadequate”. He decided to create his own food based only on the necessary nutrients for the human body, which he ordered off the Internet in mostly pill and powder form. The formula, a yellowish-beige liquid was named Soylent after “Soylent Green” – a film from 1973 where people in a dystopian future live off of mysterious wafers that turn out to be made of human flesh.

Rhinehart was able to live off Soylent for more than 30 days and it now constitutes about 90% of his diet. He is now trying to market the product as a complete food replacement for people who do not have the time or the money to consume traditional food. Soylent is now becoming a trend amongst those who drink it and people are manipulating the formula for their own specific needs. Soylent raised over $3 million dollars on the crowdfunding website Tilt, and in January, 2015 it raised $20 million in Series A funding to increase production and decrease costs to under $3 per meal. Rhinehart wants to make food so cheap that “only the rich will cook” and is hoping to use his formula to help solve global hunger.

Rob Rhinehart’s next idea for Soylent is to produce all of the nutrients of the product from bioengineered algae. Soylent partnered with Solazyme to produce algae based oil and in its current formulation 20% of the calories are made from algae. Rhinehart is hoping that algae based production can be a highly cost effective and environmentally friendly method for producing his product.

Emerging Ethics Issues as Gene Drive Technology Advances

Gene drive is the practice of “stimulating biased inheritance of particular genes to alter entire populations.” By introducing the same mutation to both chromosomes, “Selfish Genes” quickly spread through populations even if they are not advantageous to the host. Gene drive has recently been demonstrated in both yeast and in Drosophila.

Gene drive brings up bioethics issues because if a mutant strain, the mutation can spread quickly throughout an indigenous population. While this may seem bad, there are certain instances where this might be beneficial. For example, if a mutated strain of mosquitos that cannot carry malaria is released into the wild, it could prevent the transmission of the disease to humans.

As a result of the developments in gene-drive, on July 30th, 2015, the National Academy of Science held the first of several meetings over the next 15 months to find a balance between the positive and possible negative implications of gene-drive. Additionally, on July 30th Dr. Keven Esvelt, a bioengineer at Harvard Medical School and a group of his peers published a paper to define the containment strategies for gene-drive research performed in the lab. Dr. Esvelt is studying CRISPR gene-drive systems in the nematode Caenorhabditis elegan to determine what happens to the population as engineered DNA is passed on through generations. He is also testing ways of revoking the gene from the population if it becomes problematic. As our understanding and control of gene drive increases, it will be interesting to see how regulations evolve to account for this new technology.

Scientists Design First Functional Tethered Ribosome 

Researchers at the University of Illinois at Chicago and Northwestern University have engineered a tethered ribosome. During normal cellular production of protein, there are two ribosomal subunits that come together around an mRNA. After the production of protein, the ribosomal subunits separate and are able to bind to a new mRNA to produce another protein. Until now it was believed that the binding and separating of ribosomal subunits was essential for the production of protein. Ribo-T not only worked effectively in vitro, but it also worked well enough to sustain normal protein production in bacterial cells lacking wild type ribosomes.

With the advent of Ribo-T, scientists will be able to get a better understanding about ribosomal function in vivo and may be able to use Ribo-T to generate unique, functional polymers, biological therapeutics and maybe one-day create non-biological polymers.

Researchers Engineer New Biosensors to Control and Communicate With Bacteria 

A Wyss Institute team, led by Prof. George Church, has engineered new biosensors to enable a much more effective bi-directional communication with bacterial cells. The four biosensors are orthogonal to each other and rely on standardized inducible transcription regulators allowing for the precise control of gene expression.
These new biosensors effectively double the number of well-characterized and available inducible systems and are an invaluable tool for genetic engineering. When coupled with fluorescent readouts they can enable much better screening and significantly speed-up the design-test-build cycle as demonstrated in this paper.

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Afineur Begins Kickstarter Campaign

Afineur launched their innovative Kickstarter campaign to revolutionize coffee flavor via controlled fermentations on Wednesday, July 29, 2015. They reached their funding goal in under 6 hours!

Afineur uses a big data approach to identifying microbes able to specifically tailor coffee flavor through fermentations. The specific changes made are then analyzed through a combination of sensory analyzes and chromatographic tools. Their Cultured Coffee is unlike anything else, with very low bitterness, and powerful fruity, floral and chocolaty notes.

You can support Afineur on Kickstarter and get your hands on the first batch of cultured coffee right now on Kickstarter. Check their campaign here.

Ginkgo Bioworks Raises $45 million in Series B Funding

After securing $9 million in Series A funding just 4 months ago, Ginkgo Bioworks announced on July 23^rd, 2015 that they raised $45 million in Series B funding. Ginkgo is a Boston based synthetic biology company, founded in 2008 by MIT scientist Tom Knight and four recent PhD graduates. Viking Capital leads this round of funding with participation by OS Fund, Y Combinator and Felicis Ventures, who have previously invested in the company. The Series A funding was used to build Bioworks1, a robotic biofoundry system that generates genetically engineered organisms. With Bioworks1, Gingo Bioworks was able to produce yeast that made a rose fragrance for the perfume industry.

This next round of funding will be used to build a next generation biofoundry called Bioworks2 and to hire approximately 20 new employees. The company hopes that this new system will be able to generate organisms useful for the production of cosmetics, pharmaceuticals, and probiotics. With this new round of funding and the advent of Bioworks2, they are aiming to compete with Zymergen and Transcriptic to produce designer organisms.

Ginkgo Bioworks is also leading a project with DOE ARPA-e to produce microbes that utilize C1 compounds such as menthol and formate. They are also producing probiotics that eliminate antibiotic resistant bacteria.

Sean O’ Sullivan Invests in Sothic Bioscience’s Synthetic Crab Blood

Sean O’Sullivan, star of Dragon’s Den (Canada, New Zealand, Ireland and the UK’s version of Shark Tank) and founder of SOSventures invested in the startup company, Sothic Bioscience, to generate synthetic horseshoe crab blood.

As a natural defense mechanism against bacteria in shallow waters, horseshoe crab blood contains blue colored, copper molecule containing, amebocyte cells. These cells identify and congeal around invading living matter in the blood and prevent a systemic infection. Since 1970, horseshoe crab blood is the industry standard for limulus ambeocyte lysate (LAL) contamination test, which tests for gram-negative bacteria. The FDA requires intravenous drugs and any medical equipment coming in contact with the body to be first tested with horseshoe crab blood. The blood is worth about $60,000 per gallon, with a global industry of about $50 million per year.

Over 600,000 crabs care caught each year during mating season and about 30% of their blood is drained. Many of the crabs do not survive and the number of horseshoe crabs in the world is declining. This is causing the number of Red Knots, migratory birds that use horseshoe crab eggs as a food source, to decline as well. Sothic Bioscience is hoping their product will be able to replace natural horseshoe crab blood as the LAL test.

Global Bioenergies Bio-Isobutene Production Process Now Uses Sucrose

Global Bioenergies converts renewable resources into hydrocarbons through fermentation. Its focus is on the production of isobutene, an important petrochemical building block that can be converted into fuels, plastics, organic glass, and elastometers. 15 million tons of Isobutene are currently generated through fossil fuels and represents a market now worth $15 billion.

Previously, Global Bioenergies engineered a microbe that utilizes glucose to generate isbutene. They have now engineered a microbe that utilizes sucrose. This diversifies the crop-derived resources the process can use, and Global Bioenergies will be able to tap into sugar-beet derived sucrose, a staple crop in Northern Europe.

Global Bioenergies partnered with Cristal Union to build operate the first ever bio-isobutene plant, which will convert sugar beat derived sucrose into 50,000 tons of isobutene annually. Commercial production is expected to begin in 2018.

Scientists Edit Human T-Cells Using CRISPR

At UC San Francisco, scientists were able to disable the CXCR4 protein using CRISPR/Cas9 technology. CXCR4 is a protein on the surface of CD4+ T-Cells that HIV binds to and uses as an entry point into the cell. The scientists were also able to shut down PD-1, a T-cell protein that when inactivated causes T-cells to attack cancerous tumors.

Until now, scientists have not been able to utilize CRISPR/Cas9 technology to edit human T-cells. Scientists figured out a way to deliver single guide RNA into the T-cells so that they can interact with Cas9 and cut DNA at specific sequences to insert new genes. Instead of using plasmids or lentivirus, scientists combined the single guide RNA with Cas9 proteins to make ribonucleoproteins (RNPs) outside of the cell. They then exposed the T-cells to an electric field in a process called electroporation, which increases the permeability of the T-cells’ membranes and allows the entry of RNP’s into the cell. The RNPs successfully edited the genome and disabled the CXCR4 and PD-1 proteins. This technology has the potential to help individuals suffering from T-cell disorders such as HIV/AIDS, cancer, and severe combined immunodeficiency syndrome.

Using CRISPR/Cas9 to Cure Hemophilia 

Korean scientists at the Institute for Basic Science and Yonsei University have developed a method for treating hemophilia using CRISPR/Cas9 technology. Hemophilia A occurs in 1 in 5,000 male births, and is caused by a chromosomal inversion. The genetic code is essentially written backwards and the blood coagulation factor VIII (F8) gene is not expressed properly. This gene would normally allow blood to clot. Simple cuts and bruises to people with hemophilia can turn into life threatening situations.

The team used mice urinary cells with hemoplia A and turned them into pluripotent stem cells (iPSCs). CRISPR/Cas9 was then used to correct the inversion. The cells were then induced to differentiate into endothelial cells. The cells were then transplanted back into mice and expressed the corrected version of the F8 gene, which cured them of hemophilia. There also was no evidence of off target mutation resulting from the correction. According to Jin-Soo Kim, a leader of this project, this is the first time that chromosomal inversions or large rearrangements can be corrected using RGENs (RNA-guided engineered nucleases) or any other programmable nuclease in iPSCs. Although the treatment is currently only performed in a laboratory setting in mice, this research opens the possibility of helping many people affected by hemophilia.

Chemical Plants are Trying to Increase Productivity from Biomanufacturing

An interesting article overviewing the current challenges with industrial biomanufacturing was published on July 23rd, 2015. Bio-based technologies represent more than 2.2% of the US GDP ($353 billion in 2012), including the production of bulk and fine chemical manufacturing and pharmaceuticals. In order to create a better bio-production process, the Department of Energy (DOE) and the National Science Foundation (NSF) commissioned the National Academy of Science (NAS) to create a better ‘roadmap for the future’. The roadmap includes ideas ranging from creating a better feedstock and preprocessing to the development of more usable organisms and enzyme design for chemical and biological production.

In the UK, the Industrial Biotechnology and Biorefining unit Centre for Process Innovation are addressing the key problems in the industrial biomanufacturing sector. One key problem is the commercializing of R&D products because unpredictable problems arise when a product is produced on a large scale. Through large amounts of data and computational models, they are investigating the whole biomanufacturing process, including organism genetics, the reactors and separations to fix what is broken in the system. Some solutions include: using syngas to grow organisms instead of biomass from seasonal crops, and scaling production out to multiple small production systems instead of one large production facility. A worthwhile read.

Synthetic Biology Market:

Allied Market Research released a report in May 2014 detailing the projected market of Synthetic Biology until 2020. In 2013, the synthetic biology industry was valued at $3.0 billion; by 2020, it is projected to grow to $38.7 billion with a compound annual growth rate of 44.2%. The increase in value can be attributed to increased funding from government and private organizations, a growing number of research entities, and a decrease in the cost for DNA sequencing and synthesis.

According to this article, Europe has invested the most in synthetic biology and they are currently dominating the market. The most amount of growth is occurring in the Asia-Pacific region, which is investing in genetically modified foods. Enabled products and technologies are dominating the market, while enabling products and technologies are expected to see the most amount of growth. The market for diagnostics and pharmaceuticals is expected to remain the largest for all applications of synthetic biology and biofuels is expected to see the most amount of growth.

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Public consultation on the preliminary opinion on Synthetic Biology III: Research Priorities

Last week, the European Commission released to the general public a preliminary version of the third and final opinion on research priorities in synthetic biology. A consortium of three scientific committees and experts in the field, including those at Synbio Consulting, advised the Commission on issues relating to public health, consumer safety, and the environment. In the previous opinions, we defined synthetic biology to be “the application of science, technology and engineering to facilitate and accelerate the design, manufacture and/or modification of genetic materials in living organisms”.

The second opinion discussed whether the current regulations of the European Union for genetically modified organisms are adequate in regulating the risks for human and animal health and the environment and suggestions were provided for changes to the risk assessment procedures and risk mitigation procedures, including safety locks.

In this third opinion, major gaps in knowledge necessary for proper risk assessment are identified and research topics that would help close those gaps are suggested. This opinion is written to mitigate risks for the foreseeable future, but will need to be updated to include the social, ethical, governance, and security implications of synthetic biology as well as human embryonic research. The European Commission is currently seeking consultation from the public about this third opinion. If you have any comments, suggestions, explanations, contributions or any other scientific information that you feel the group should investigate, please submit your written comments here.

BioBuilder: Synthetic Biology in the Lab Now in Stores! 

BioBuilder: Synthetic Biology in the Lab is a new book written by Natalie Kuldell, PhD., Rachel Bernstein, Kathryn M Hart and Illustrated by Karen Ingram. It is a wonderful introduction to synthetic biology. Developed at MIT in collaboration with award winning high school teachers, the book allows for both teachers and students to get the background information to get involved in the newly emerging synthetic biology field.

Based on BioBuilder’s curriculum, this book provides instruction for hands-on learning for secondary or post-secondary classrooms and laboratories. It  teaches the fundamentals of synthetic biology, the key aspects that researchers are investigating in the lab, and ethical issues associated with synthetic biology.  In addition, students will learn the “design, test, build cycle”, test synthetic organisms built in a lab, measure variants of an enzyme-generating genetic circuit, investigate “bacterial photography”, or even build living systems to generate a diversity of colorful pigments. Pick up a copy today!

Intrexon and Fibrocell Announce IND Filing for Treatment of Recessive Dystrophic Epidermolysis Bullosa (RDEB)

On July 20th, 2015, Intrexon and Fibrocell announced their filing of an Investigational New Drug (IND) Application for FCX-007 for the treatment of recessive dystrophic epidermolysis bullosa (RDEB). Intrexon, a leader in the synthetic biology industry, and Fibrocell, a company committed to the treatment of rare skin and connective tissue disorders, teamed up to create this innovative product for a disease that currently has no cure.

RDEB is a rare genetic connective tissue disorder, caused by a mutation in the COL7A1 gene that codes for type VII collagen, which forms anchoring fibrils between layers of the skin. This disease currently affects 1,100 – 2,500 Americans and causes skin layers to separate causing blistering, open wounds, and scarring during daily activities, such as rubbing or scratching and often leads to death. Children affected by this disease are often called “butterfly children” because their skin is as delicate as the wings of a butterfly.

FCX-007 is a novel gene therapy treatment for RDEB. It is a cultured genetically modified autologous fibroblast that encodes COL7, ex-vivo, which is then injected at local blister and wound sites. This allows for more effective and localized treatment of affected areas instead of systemic treatment. In pre-clinical studies, there were no findings of toxicology in RDEB human skin xenograft severe combined immunodeficiency (SCID) mice. Additionally, COL7 was found in dermal-epidermal junctions of RDEB cultured grafts in RDEB human skin xenograft SCID mice and there was no apparent systemic distribution of the vector in human skin xenograft SCID mice. These positive proofs of concept are allowing Intrexon and Fibrocell to initiate Phase I/II clinical trials by the end of this year.

Events:

4th Annual Sc2.0 & Synthetic Genomes Conference

On Thursday July 16th and Friday July 17th, 2015, the 4th Annual Sc2.0 & Synthetic Genomes Conference took place at New York Genome Center in New York City. The Synthetic Yeast Genome Project, Sc2.0, is attempting to generate an entirely synthetic genome for the yeast Saccharomyces cerevisiae. The conference discussed the collaborative effort of the Sc2.0 Research Consortium to generate 16 synthetic chromosomes of the designer genome. Genome engineering efforts, CRISPRs and designer nucleases and synthetic biology were also discussed. In addition, there was a panel discussion on genome engineering, industry and society, and keynote speakers from lab automation and DNA synthesis industries gave presentations. Look out for the next edition!

SynBioBeta Activate! Cambridge, UK 2015

On July 27th, 2015, SynBioBeta is holding their annual SynBioBeta Activate! conference in Cambridge, UK. It will be held at Old Divinity School, St. John’s College, Trinity Street, Cambridge, UK from 5-9:30pm. The topic of discussion is Reprogramming Life With Synthetic Biology.

There will be presentations from a number of leading companies in the synthetic biology industry and discussions around new tools and the open source innovation. The schedule is as follows:

5:30-6:00 – Arrival and Networking
6:00-6:30 – Synthetic Biology: New Tools for an Industry at an Inflection Point
6:30-7:15 – SynBio Company Showcase
7:15-7:45 – Panel: Can Open Source Biological Innovation Succeed?
7:45-9:00 – Drinks, Finger Buffet and Networking

Tickets are £5.00 for students and £10.00 for everyone else.

Register here!

That’s it for this week’s Synthetic Biology Mashup! A suggestion or a question? Shoot us an email!

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Review of the Memorandum for Heads of the FDA, EPA, and USDA

On July 2, 2015, a memorandum was released for the heads of the United States Food and Drug Administration (FDA), Environmental Protection Agency (EPA), and the Department of Agriculture (USDA) to modernize the Federal regulatory system for biotech products and to establish periodic updates of the system. The purpose of this memorandum is to keep public confidence in the system high, allowing for the best novel scientific breakthroughs to be brought into the economy by preventing barriers to future innovation and development, improving coordination, transparency and efficiency throughout the industry, all while protecting human and animal health and the environment through risk assessment and regulation. The memorandum also sought to divide the responsibility of regulation across the three government agencies. The principals outlined in this memorandum have now been applied to the regulatory framework for the biotechnology industry, including Synthetic Biology.

Data Storage for Genetic Information

Stevens, et al. published an article on July 7, 2015 comparing future data storage of genomes to Big Data domains such as astronomy, Twitter, and Youtube. Genome sequencing is becoming more popular and less expensive and has implications in scientific discovery and personalized medicine. Currently the Sequence Read Archive (SRA) maintained by the United States National Institutes of Health (NIH) holds raw sequenced data of 32,000 microbial genomes, 5,000 plant genomes, and 250,000 individual human genomes. Although it seems to be a very high estimate, the authors of this article believe, 100 million to as many as 2 billion individual human genomes and 1.2 million plant and animal genomes for energy, environmental and agricultural purposes will be sequenced by the year 2025. The actual number of genomes sequenced will depend on a number of factors including decreasing the price of sequencing a genome (currently about $1,000 per genome), whether the computational technology to store the all of the data will be developed, willingness of the public to sequence their genomes, and government regulations preventing the sequencing of genomes outside of medical purposes. Additionally, it will be important to develop an adequate secure storage system, to prevent confidential medical information being released to the public. Figure 1: Projected growth of genomic sequencing technology. Source: Stephens, ZD., et al., Big Data: Astronomical or Genomical? PLoS Biology, 2015.

MIT Researchers Develop Computing Elements for Bacteria in the Gut

In a paper published in Cell on July 9, 2015, researchers at MIT modified basic computing elements in the bacterium Bacteroides thetaiotaomicron, a prevalent and abundant commensal bacterium of the human gut. These sensors, memory switches, and circuits are able to respond to signals in the gut and could potentially be used for for surveillance of or therapeutic delivery to the gut microbiome. Prior to this achivement, genetic circuits were only built inside of model organisms such as E. coli that is present only in low concentrations in the gut. Once an environmental stimulus, such as a food additive, has been detected by this genetically modified bacterium, genes can be turned on or off for controlled treatment of inflammation or cancerous tissue. The bacterium is also engineered to remember the environment by transcribing recombinases, which record information into bacterial DNA by recognizing specific DNA sequences and inverting their direction. Creating genetic circuits in commensal bacteria will potentially allow for non-invasive monitoring of the gut, long-term targeted therapeutics, and further functional studies of the digestive tract. If you would like to learn more, please read the published paper!

DEINOVE Partners with POS Bio-Sciences to Produce Carotenoids

DEINOVE, a French biotech company that uses Deinococcus radiodurans bacteria for the production of biofuels and bio-based chemicals recently partnered with Canada’s POS Bio-Sciences for the development, extraction and purification of carotenoids. POS Bio-Sciences is a leader in the extraction of high value compounds, such as carotenoids. D. radiodurans is an extremophile bacterium that can withstand large amounts of ionizing radiation, cold, dehydration, vacuum and acid. In recent years, DEINOVE’s DIENOCHEM division has been working to create a strain of D. radiodurans to increase its natural propensity to produce carotenoids. Humans and animals do not produce carotenoids de novo and carotenoids must be consumed from diet. Carotenoids prevent cancer, heart disease, inflammation, and vitamin A deficiency and promote eye health. They are also used in food coloring. The global market for carotenoids is expected to be $1.4 billion by 2019, with an estimated annual growth rate of 3.5%. To learn more, please read DEINOV’s press release!

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A Small Overview of a Piece We Recently Published in Science Careers

Training the next generation of leaders for the bio-industry is a great challenge. Most graduate programs are still geared towards tenure track and do not reflect the reality of the work place. Data published in the National Science Board’s 2014 Science and Engineering Indicators show that a mere 29% of newly graduated life science PhDs will find a full time faculty position.

With our colleague, Dr. Jim Philp from the Organization for Economic Co-operation and Development, we wrote a small piece for Science Careers to assess the situation and give pointers to better train the next generation of leaders in the Synthetic Biology industry. We provide here a few takeaways, but make sure to read the full article on Science Careers.

As defined by the European Commission, Synthetic Biology is “the application of science, technology and engineering to facilitate and accelerate the design, manufacture and/or modification of genetic materials in living organisms.” Although the field is in its infancy stage, it has been estimated that the global market for synthetic biology will reach $39 billion by 2020 in industries such as climate change, energy consumption, environmental protection, and health care. Facing such a potential, educational institutions ought to adapt and propose a diverse range of programs spanning not only basic science but also entrepreneurship and management.

A great getaway for students to get involved in the synthetic biology industry is to compete in an international synthetic biology competition such as the International Genetically Engineered Machine competition (iGEM). There are also more than 100 universities now involved in educating future synthetic biologists at the Masters and Ph.D. levels. Scientists interested in the field usually have backgrounds in mathematics, physics, computer sciences, chemistry, biology, and medicine.  This diversity of backgrounds and inherent interdisciplinary nature of the field makes for interesting educational challenges.

Beyond academic programs, navigating and understanding and capitalizing on the exciting options to transition into business and entrepreneurship might prove overwhelming. There are no MBAs specific for the synthetic biology industry, MBAs geared towards the biotechnology and chemical industries may be a good starting. Beyond this the international Synthetic Biology Leadership Accelerator Program (LEAP) can help synthetic biology change-makers and support them to positively impact the field. Last but not least, a number of startup accelerator such as Indie.Bio are starting to provide financial support and mentorship to early-stage synthetic biology startups.

Make sure to read the full article on Science Careers and let us know if you have any questions! Info@Synbioconsulting.com.

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The OTI identifies, assesses, recommends R&D strategy, and invests seed funding in newly emerging technology. Synthetic biology, as defined by the European Commission “is the application of science, technology and engineering to facilitate and accelerate the design, manufacture and/or modification of genetic materials in living organisms”. Products from the synthetic biology industry help contribute $350 billion dollars per year to the U.S. economy in industries including: food, clothing, medicine and cosmetics. Because the synthetic biology products can be used in a variety of industries, including healthcare, agricultural, and industrial, government agencies, including the Department of Energy, the National Science Foundation and the DoD, including DARPA, invest over $220 million annually into synthetic biology research and development. The DoD has identified and assessed specific potential uses for synthetic biology technology including, generating commodity and specialty materials, increasing health and performance of soldiers on the battlefield, using biological systems as sensors, and defense against biological and chemical warfare.

Commodity Materials

Commodity materials that the DoD can create using synthetic biology include cheaper textiles and fuels. In the commodity sector, the DoD is investing most in the production of fuels in warzones, such as in Afghanistan, where a gallon of fuel can cost as much as $400.

Specialty Materials

Some biological systems are able to naturally produce materials that are difficult, expensive, or impossible to produce by traditional means. Potential defense applications include: sensor active materials, high strength polymers for armor, stealth materials, corrosion resistant coatings, biological computing; data storage and cryptographic materials. With the exception of DARPA’s Living Foundries project, that is creating organisms that can generate 1000 molecules, there is very little private and government funding in specialty materials. The DoD is planning on focusing most of their efforts and funding on R&D. One such effort, released in late 2014, is the Synthetic Biology for Materials prize from a partnership between the OTI and the Materials and Manufacturing Directorate of the Air Force Research Laboratory that rewards the best metamaterial (materials that are engineered to have properties that have not been found in nature) R&D plans.

Sensing

The DoD is looking to utilize natural biologically occurring sensing for their benefit. For example, certain biological systems can naturally or synthetically detect electromagnetic waves, light and ionizing radiation. These organisms can produce physical or chemical signals, which scientists can harvest to create living sensors and detect changes in an environment. Because of their small size, high sensitivity, ability for self-replication, multiple stimulus sensing ability and the difficulty of distinguishing synthetic vs. organic organisms in the environment, synthetic organisms can become very accurate and discrete sensors for military applications. Potential applications include: distributed tag, track and trace systems and persistent clandestine sensors. There will be some regulations that the DoD will need to overcome to implement these sensors in the field as introducing genetically modified organisms into the natural environment can potentially have unintended consequences, such as gene transfer with organisms in the natural environment. Most of DoD funding is going to R&D and to lobbying for policy to be able to implement the sensors into the field.

Medical and Human Performance Modification

Outside of trauma, most of the DoD’s focus is on human performance modification. Potential applications of synthetic biology in this industry include: prophylactic application of bacteria on the skin to prevent infection and to help heal wounds and probiotics that decrease the effects of stress and enhance mental performance. It will, however, be difficult to get these products approved by the FDA and the DoD is focusing much of its resources elsewhere.

Defense Against Biological and Chemical Warfare

The United States will not use chemical and biological warfare. That does not mean that adversaries will not use synthetic biology to create novel virulent strains of bacteria, viruses or chemical weapons. The DoD (mainly DARPA) and healthcare organizations are creating treatments for potential biological and chemical threats to protect both citizens and warfighters.

Human Capital

At this time, there are very few highly experienced program managers, scientists, and experts in the Synthetic Biology Department at the DoD. It takes approximately twenty years to train a junior-level scientist to a senior rank. The DoD is looking to train junior level post-doctoral students to work within the field of synthetic biology so that the field remains fruitful.

Download the full DoD Synthetic Biology report here. If you have any questions about the synthetic biology industry, feel free to contact us at Info@Synbioconsulting.com.

The post The Department of Defense Technical Assessment of Synthetic Biology – An overview appeared first on Synthetic Biology Consulting.

Programmable Bacteria within the Mammalian Gut

The Silver lab at Harvard Medical School recently programed bacteria to detect and record an environmental signals in the mammalian gut in the hopes of using them for diagnostic purposes. They engineered a strain of E. coli bacteria to react to the presence of a anhydrotetracycline and the response was an inheritable change in state based on the cl/Cro system from phage lambda. This change detectable after retrieval of the bacteria from mice guts. Moving forward, the researchers hope to be able to detect a larger range of more medically relevant triggers and increase the length of time over which the response is detectable. The ultimate goal of the project would be to engineer bacteria that not only detect medically relevant conditions, but also respond in a proactive manner, thus creating  dynamic and living therapies.

Saving the American Chestnut Using Genetic Engineering

This week the Motley Fool investigated the history of the American chestnut tree. From its recent near extinction due to the accidental importation of Chinese fungus Cryptonectria parasitica, to the current efforts to reestablish its population, Chestnut trees have had a central role in the economy, environment and cultural history of the USA. Now a team from the State University of New York are using precise genetic engineering techniques to introduce wheat resistance genes coding for an enzyme capable of neutralising the acid produced by the pathogenic fungus into chestnut seeds. The team led by Dr Powell has already created a “prototype” tree, called Darling 4 American chestnut that displays a significant increased resistance, and are preparing to conduct field tests on an even more resistant prototype, Darling 311. The article showcases the advantages of genetic engineering compared to the use of cross-breeding techniques in the current GMO debate.

International Collaboration to Develop Stress-Resistant Rice

Rice is an incredibly important staple food all over the world. However, it is sensitive to rainfall levels and soil salinity. As climate change renders rain patterns more erratic and as soil salinity increases, rice crop may further suffer. In response, a collaborative effort between researchers from the International Center for Genetic Engineering and Biotechnology in New Delhi, the Tamil Nadu Agriculture University in Coimbatore, Southern India and the Queensland University of Technology in Australia are working on introducing stress-resistance genes from a highly resistant Australian grass into rice to produce a genetically-engineered rice strain which will ensure continued crop volume regardless of environmental challenges. This three-year project is jointly funded by the Indian and Australian governments.

Innovative Genomics Initiative Launched in California

The University of California Berkeley and University of California San Francisco are teaming together to launch the Innovative Genomics Initiative (IGI). The IGI is built up around CRISPR/Cas9, a discovery made by Berkeley Professor Doudna’s team. CRISPR/Cas9 has the potential to enable researchers to target specific genes in order to study and combat genetic diseases more specifically, accurately, and efficiently than ever before. In less than two years since its publication, the work has been used in over 125 other publications and is the foundation for several start-up companies. As Prof. Doudna explains, “the main goal of the initiative is to develop the CRISPR/Cas9 technology for applications in human health, and create a library of research resources that will make it available broadly.”

Synthetic Biology Flash News

EnEvolv, the small company co-founded last year by George Church, received last week its first round of financing, $1.7M from Cultivian Sandbox Venture Partners. EnEvolv aims at using Multiplex Automated Genome Engineering (MAGE) to engineer and license microorganisms to produce chemicals, enzymes, and small molecules for pharmaceuticals, personal care, specialty chemicals, food, and energy industries.

SynBio Consulting Founder, Camille Delebecque, was interviewed this week in the French biotech news website LaBiotech.fr

That’s it for this week’s Synthetic Biology Mashup! A suggestion or a question? Shoot us an email!

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Expending Synthetic Biology’s toolbox by engineering light-operated genetic circuits

Scientists at Rice University have developed light-induced genetic circuits in bacteria operating as function generators and capable of producing finely tuned linearized dynamics, sinusoidal oscillations, and complex waveforms. These cells were engineered using optogenetics. The technique, primarily used in neurosciences to control neuronal activities uses light-sensitive membrane proteins to render cells sensitive to specific wavelengths of light. The engineered bacteria were activated using LEDs and monitored through a fluorescence output. The toolset developed in this work published in Nature Methods should facilitate the design and engineering of biological systems.

TeselaGen’s Rapid Prototyping platform featured in TechCrunch

The boundary between technology and biology is becoming thinner and thinner. This week, as a reminder, we have the famous news website focused on information technology companies TechCrunch publishing an article about Synthetic Biology company TeselaGen. TeselaGen has built a software platform and a set of sequence editing tools that they hope will assist in rapid prototyping for synthetic biology. Their tool can be used to view and edit sequence in compliance with the Synthetic Biology Open Language standard. It will be free for academics and available as a paid subscription for commercial use.

Fireblight Resistant Apples Developed by ETH Zurich and Julius Kühn Institute

Plant Biotechnology Journal published an article this week detailing the successful creation of fireblight resistant apples by ETH Zurich and Julius Kühn Institute. Fireblight is a bacterial infectious disease affecting fruits of the Rosaceae family, costing millions to farmers annually throughout the world. Researchers identified a resistance gene (FB_MR5) from a wild apple and introduced it into the farmed Gala apple using cis-genetic engineering techniques. The gene encodes a protein that recognises the pathogenic bacterium’s surface proteins and initiates a defence mechanism within the plant. The engineered plants have shown resistance in greenhouses.

Synthetic Biology Flash News

Precision Biosciences, a genome engineering technology company, and Agrivida, a company focusing on enzyme solutions, entered this week into a trait development collaboration agreement for the modification of genes through the Directed Nuclease Editor tool, property of Precision.

Intrexon acquired a high-tech laboratory in Budapest from Codexis Inc., a biocatalyst developer. This move strengthens Intrexon’s presence in strain and protein development, as well as its presence in Europe.

That’s it for this week’s Synthetic Biology Mashup! A suggestion or a question? Shoot us an email!

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