Tag Archives: genetic engineering and military

Genome Integrity and the Unsafe Genes

DARPA created the Safe Genes program to gain a fundamental understanding of how gene editing technologies function; devise means to safely, responsibly, and predictably harness them for beneficial ends; and address potential health and security concerns related to their accidental or intentional misuse. Today, DARPA announced awards to seven teams that will pursue that mission, led by: The Broad Institute of MIT and Harvard; Harvard Medical School; Massachusetts General Hospital; Massachusetts Institute of Technology; North Carolina State University; University of California, Berkeley; and University of California, Riverside. DARPA plans to invest $65 million in Safe Genes over the next four years as these teams work to collect empirical data and develop a suite of versatile tools that can be applied independently or in combination to support bio-innovation and combat bio-threats.

Gene editing technologies …[can] selectively disable cancerous cells in the body, control populations of disease-spreading mosquitos, and defend native flora and fauna against invasive species, among other uses. The potential national security applications and implications of these technologies are equally profound, including protection of troops against infectious disease, mitigation of threats posed by irresponsible or nefarious use of biological technologies, and enhanced development of new resources derived from synthetic biology, such as novel chemicals, materials, and coatings with useful, unique properties.

Achieving such ambitious goals, however, will require more complete knowledge about how gene editors, and derivative technologies including gene drives, function at various physical and temporal scales under different environmental conditions, across multiple generations of an organism. In parallel, demonstrating the ability to precisely control gene edits, turning them on and off under certain conditions or even reversing their effects entirely, will be paramount to translation of these tools to practical applications…

Each of the seven teams will pursue one or more of three technical objectives: develop genetic constructs—biomolecular “instructions”—that provide spatial, temporal, and reversible control of genome editors in living systems; devise new drug-based countermeasures that provide prophylactic and treatment options to limit genome editing in organisms and protect genome integrity in populations of organisms; and create a capability to eliminate unwanted engineered genes from systems and restore them to genetic baseline states. Safe Genes research will not involve any releases of organisms into the environment; however, the research—performed in contained facilities—could inform potential future applications, including safe, predictable, and reversible gene drives….

A Harvard Medical School team led by Dr. George Church seeks to develop systems to safeguard genomes by detecting, preventing, and ultimately reversing mutations that may arise from exposure to radiation. This work will involve creation of novel computational and molecular tools to enable the development of precise editors that can distinguish between highly similar genetic sequences. The team also plans to screen the effectiveness of natural and synthetic drugs to inhibit gene editing activity.

A North Carolina State University (NCSU) team led by Dr. John Godwin aims to develop and test a mammalian gene drive system in rodents. The team’s genetic technique targets population-specific genetic variants found only in particular invasive communities of animals. If successful, the work will expand the tools available to manage invasive species that threaten biodiversity and human food security, and that serve as potential reservoirs of infectious diseases affecting native animal and human populations….

A University of California, Berkeley team led by Dr. Jennifer Doudna will investigate the development of novel, safe gene editing tools for use as antiviral agents in animal models, targeting the Zika and Ebola viruses. The team will also aim to identify anti-CRISPR proteins capable of inhibiting unwanted genome-editing activity, while developing novel strategies for delivery of genome editors and inhibitors….

A University of California, Riverside team led by Dr. Omar Akbari seeks to develop robust and reversible gene drive systems for control of Aedes aegypti mosquito populations.

Excerpts from Building the Safe Genes Toolkit, DARPA Press Release, July 19, 2017

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60 Days to Save the World

A dendritic cell. image from wikipedia

The US military supports US Government responses to public health emergencies such as Ebola, which can cause regional destabilization and spread through global travel. Warfighters must also operate in regions where diseases like chikungunya and dengue are endemic, and even seemingly mild challenges like seasonal influenza affect force readiness. In addition to these naturally occurring threats, terrorists and other potential adversaries have a growing palette of biological tools to engineer new biological threats. Existing capabilities to respond to an outbreak and develop therapeutics often take years or even decades to achieve results. Recent examples of public health emergencies have demonstrated a national and global inability to develop effective preventive or therapeutic solutions in a relevant timescale when an infectious threat emerges. The threat of infectious agents on US and global national security can be mitigated if the DoD has the capability to rapidly deploy and impart near-immediate immunity to military personnel and civilian populations for known and newly emerging pathogens.

The goal of P3 is to achieve an integrated capability that can deliver pandemic prevention countermeasures to patients within 60 days of an outbreak. P3 aims to revolutionize outbreak response by enabling rapid discovery, characterization, production, and testing of efficacious medical countermeasures. P3 will innovate in the following areas: (1) Generation of virus stock (including viral unknowns); (2) Rapid evolution of antibody candidates; and (3) Gene-encoded antibody delivery methods.

Excerpts from  The Biological Technologies Office (BTO) of the Defense Advanced Research Projects Agency (DARPA) Proposers Day March 2, 2017 

The Manipulation of Insects: DARPA

Insect Allies program DARPA

DARPA’s Biological Technologies Office s working on new Insect Allies program. Insect Allies will seek to develop vector[insect]-mediated modification technologies for mature plants to rapidly counter environmental and biological threats to crops. Threats might include pathogens, pests, drought, and salinity, among others. DARPA believes that the high specificity of genetic modification coupled with quick plant gene uptake could allow crops to be protected from threats within a single growing season.The Proposers Day will be held on November 18, 2016

Excerpt from  DARPA Press Release Insect Allies Proposers Day, Nov. 2016

Synthetic Biology and DARPA

silica

Twist Bioscience announced that it raised $26 million in a Series B financing to commercialize the company’s semiconductor-based synthetic gene manufacturing process. Nick and Joby Pritzker, through their family’s firm Tao Invest, led the round, with participation from ARCH Venture Partners, Paladin Capital Group, Yuri Milner and additional strategic corporate and venture investors. All existing investors participated in the round.

The company also received a $5.1 million contract from the Defense Advanced Research Projects Agency (DARPA) to fund development of Twist’s technology platform for the large-scale, high-throughput construction of genetic designs. DARPA granted the contract under the Living Foundries: 1000 Molecules Program, which seeks to build a scalable, integrated, rapid design and prototyping infrastructure for the facile engineering of biology…

Said Emily Leproust, Ph.D., chief executive officer of Twist Bioscience. “Today, we have all the necessary components in place to automate and scale our synthetic gene manufacturing process and staff strategically, with the goal of bringing our first products and services to the market in 2015.”

According to to Twist Bioscience “At Twist Bioscience, our expertise is synthetic DNA. We have developed a proprietary semiconductor-based synthetic DNA manufacturing process featuring a 10,000-well silicon platform capable of producing synthetic biology tools, such as oligonucleotides, genes, pathways, chassis and genomes. By synthesizing DNA on silicon instead of on traditional 96-well plastic plates, our platform overcomes the current inefficiencies of synthetic DNA production, and enables cost-effective, rapid, high-quality and high throughput synthetic gene production. The Twist Bioscience platform has the potential to greatly accelerate the development of personalized medicine, sustainable chemical production, improved agriculture production as well as new applications such as in vivo diagnostics, biodetection and data storage. 

Twist Bioscience Secures $31.1 Million,  PRESS RELEASE, May 27, 2014

See also DARPA and Industrial Revolution in Genetic Engineering

See also DARPA Biological Technologies Office

DARPA Pushes for Industrial Revolution in Genetic Engineering

From DARPA’s Website: Living Foundries

[Current State of Bio-engineering]

Current approaches to engineering biology rely on an ad hoc, laborious, trial-and-error process, wherein one successful project often does not translate to enabling subsequent new designs. As a result, the state of the art development cycle for engineering a new biologically manufactured product often takes 7+ years and tens to hundreds of millions of dollars (e.g. microbial production of artemisinic acid for the treatment of malaria and the non-petroleum-based production 1,3-propanediol).

[DARPA Goal]

Transforming biology into an engineering practice would enable on-demand production of new and high-value materials, devices and capabilities for the Department of Defense (DoD) and address complex challenges that today have no or few solutions.

The Living Foundries Program seeks to create the engineering framework for biology, speeding the biological design-build-test cycle and expanding the complexity of systems that can be engineered. The Program aims to develop new tools, technologies and methodologies to decouple biological design from fabrication, yield design rules and tools, and manage biological complexity through abstraction and standardization. These foundational tools would enable the rapid development of previously unattainable technologies and products, leveraging biology to solve challenges associated with production of new materials, novel capabilities, fuel and medicines. For example, one motivating, widespread and currently intractable problem is that of corrosion/materials degradation. The DoD must operate in all environments, including some of the most corrosively aggressive on Earth, and do so with increasingly complex heterogeneous materials systems. This multifaceted and ubiquitous problem costs the DoD approximately $23 Billion per year. The ability to truly program and engineer biology, would enable the capability to design and engineer systems to rapidly and dynamically prevent, seek out, identify and repair corrosion/materials degradation.

Accomplishing this vision requires an approach that is more than multidisciplinary – it requires a new engineering discipline built upon the integration of new ideas, approaches and tools from fields spanning computer science and electrical engineering to chemistry and the biological sciences. The best innovations will introduce new architectures and tools into an open technology platform to rapidly move new designs from conception to execution.  Performers must ensure and demonstrate throughout the program that all methods and demonstrations of capability comply with national guidance for manipulation of genes and organisms and follow all guidance for biological safety and Biosecurity.

A Broad Agency Announcement (BAA) solicitation for phase one, Advanced Tools and Capabilities for Generalizable Platforms (ATCG), closed in November, 2011. The BAA called for the development of the advanced, translatable tools and capabilities that will make up an end-to-end technology platform for rapidly, safely and predictably engineering biological production systems. The goals of these advanced tools and capabilities are to compress the biological design-build-test cycle by at least 10x in both time and cost while increasing the complexity of the systems that can be designed and executed by orders of magnitude. These advancements should enable the ability to rapidly design and build new systems to create novel capabilities and to address complex challenges.

See Amyris