Needle in a Haystack: Looking for Compounds to Treat COVID-19

In late March, a group of researchers at the University of California, San Francisco published a preprint describing a protein-protein interaction map that could find potential drug targets against SARS-CoV-2. Their study looked for interactions between every viral protein and every human protein, with the idea that molecules known to bind those human proteins might disrupt the interaction with the viral protein, therefore interfering with the viral life cycle. Several hundred hits were identified, and of those hits, over 50 protein targets had known small molecule binding partners, so-called “druggable” targets. These small molecules could potentially interfere with viral protein binding and therefore be repurposed against COVID-19. One interaction was observed between the viral protein Nsp13 and human centrosomal protein 250 (CEP250), a protein target previously predicted to be too flat for small molecule drugs to bind to it and therefore “undruggable”.

Several years ago, our team at Warp Drive Bio performed a very different high throughput screen, searching for human proteins that could bind to a novel natural product that the team had discovered. The molecule, called WDB002, is made by a species of soil-dwelling Streptomyces bacteria that was identified using Warp Drive Bio’s genome mining technology. WDB002 was found to be a strong binder to a little appreciated human protein called CEP250 — the same protein identified in the recent SARS-CoV-2 study! WDB002 first binds to another human protein, FKBP12, which then forms a tight three-part complex with a portion of CEP250.

In October 2018, Revolution Medicines bought Warp Drive Bio, and Ginkgo then acquired the Warp Drive genome mining platform from Revolution Medicines in January 2019. Today PNAS published an article authored by members of the former Warp Drive Bio team, showing how WBD002 and its related molecules can bind to the “coiled-coil” domain in CEP250, in complex with FKBP12 via binding studies and crystal structures. These coiled-coil domains are very “flat” and therefore notoriously difficult targets for drug discovery, which makes the tri-complex modality potentially useful for finding leads against other so-called “undruggable” disease targets.

As for CEP250’s role in COVID-19, we don’t know yet whether WDB002 will be useful for treating the virus, but Ginkgo is committed to finding out. Revolution Medicines has licensed intellectual property to Ginkgo to answer this question. Our team has already produced a batch of pure WDB002 from Streptomyces. Now, we are testing how it behaves in an in vitro live virus assay in collaboration with research groups that can perform these studies at biosafety level 3. It’s been exciting to be part of the story of WDB002, from when it was first discovered to exploring its potential as an antiviral. Despite the unknowns inherent in drug discovery and development, it is inspiring to witness Ginkgo’s ability to apply its platform towards vaccines, therapeutics, and diagnostics for COVID-19. We hope to share news about the WDB002 project in the coming months.

Concentric by Ginkgo: COVID-19 testing at scale

To learn more about how Concentric by Ginkgo can support you and your organization, please contact us.

Today we’re thrilled to announce the launch of Concentric by Ginkgo. Concentric offers COVID-19 testing at scale to support schools and businesses in their reopening strategies and provides end-to-end, on-site testing services for organizations that seek to make testing available to their communities.

Everybody’s health is connected. Many layers of public health response are necessary to predict, understand, control, and eventually end a pandemic. Testing is a major pillar of such a response and increased testing capacity is critical for enabling informed public health decisions and contact tracing programs. While national capacity has grown significantly in recent weeks, there is still a large, unmet need for more testing, and experts believe that millions of tests per day are needed for the United States to contain and slow the spread of COVID-19.

We’re developing large-scale testing capacity for Concentric by Ginkgo with next generation sequencing (NGS), which allows us to read, process and analyze many DNA and RNA samples in parallel on one machine. You can read more about the differences in testing methods in our white paper. We’re also working toward obtaining an Emergency Use Authorization for a COVID-19 test for our CLIA certified laboratory with the goal of scaling testing further. At the present time, to serve current reopening needs of businesses and educational organizations, Concentric by Ginkgo will work with other CLIA-certified labs offering RT-PCR based tests to make on-site testing programs available immediately.

We chose the name Concentric to highlight the interconnected communities we exist in, the different layers of proximity each of us have, and the ripples of impact that our choices send out into the world. As we grow Ginkgo, we’re excited to expand our foundries to enable more cell programming projects across many industries, now alongside Concentric.

Read more on Concentric’s efforts in our CNBC article and interview. To learn more about partnering with Concentric by Ginkgo to support your organization’s COVID-19 testing strategy, visit concentricbyginkgo.com to contact us.

How to Deploy Millions of COVID-19 Tests Per Day

There is broad agreement within the public health community that the path out of the COVID-19 lockdown is through widespread testing to catch new infections, tracing to find everyone who may have been infected, and supported isolation to prevent further spread of the virus. There is little agreement, however, that the technology and infrastructure exists today to meet that need.

With so much at stake—countless lives and billions of dollars—speed is of the essence in scaling up COVID-19 testing. We’ve put together a brief white paper providing an assessment of existing and emerging testing methods and outlines a path by which the United States can rapidly scale up the infrastructure that enables millions of tests per day.

To rapidly increase the scale of COVID-19 testing, the United States should:

  • Continue to scale up testing methods already in use, such as RT-qPCR as well as isothermal nucleic acid methods, by expanding the number of testing machines and kits.
  • Leverage the country’s vast genomic sequencing capacity by repurposing it to dramatically augment testing capacity.
  • Invest in the development of massively distributable, cheap, point-of-use tests, such as antigen-based tests, and be prepared to deploy them as soon as they become available.
  • Make testing widely available, beginning with those at highest risk, regardless of symptoms, insurance reimbursement, or other impediments.
  • Scale up testing to enable screening of significant portions of the workforce and integrate screening effectively with contact tracing.

 

You can access a PDF version of our report here. We welcome your feedback—please reach out to us at [email protected].

 

Teaming Up to Improve Antibody Therapeutics for COVID-19

In response to the COVID-19 pandemic, many groups across academia, biotech, and pharma are working hard to develop antibody therapeutics against SARS-CoV-2. Antibodies from patients who have recovered from COVID-19 may be effective in the treatment of critically ill patients, and many groups are seeking plasma donations to help those in need. In the long term, however, different approaches are needed to make effective antibody treatments available on a much larger scale.

Precisely engineered antibodies make up some of our most effective medicines. New antibodies can be based on those identified in convalescent patients, by reusing related antibodies (e.g., those effective against SARS), by screening antibody libraries, or by using computational methods to design new antibodies. As researchers discover and design new antibodies against SARS-CoV-2, many need help to rapidly produce and test these antibodies in preclinical studies. As part of our broader effort against COVID-19, we’re joining our friends at Berkeley Lights in their Global Emerging Pathogen Antibody Discovery Consortium to support the rapid development of promising candidate antibodies into useful treatments.

The consortium brings together many groups that are working to develop assays using the Berkeley Lights Beacon platform to quickly scale up the studies needed to advance new therapeutic antibodies against COVID-19 or any future emerging diseases. As a consortium member and in partnership with organizations that are designing new antibodies, Ginkgo will be using our automated high-throughput tools to reduce the preclinical development time for novel antibodies, through:

  • Synthesis of large numbers of antibody genes;
  • Expression of large numbers of antibodies in mammalian cells;
  • High-throughput screening of those antibodies for antigen binding as well as critical functional properties including virus neutralization, antibody-dependent enhancement of infectivity, and cross-reactivity with blood proteins; and
  • Optimization of lead antibodies for better stability, solubility, decreased  immunogenicity, and reduced cross-reactivity.

We have been so inspired by how the biotech community has come together so quickly in response to COVID-19, and we’re thrilled to be part of this consortium bringing together the people and tools to help accelerate a next generation of therapeutics. As with many aspects of Ginkgo’s COVID-19 response, this antibody-related work was a capability that we were developing that is now being put on an accelerated timeline.

If you’re working to discover new antibodies or other therapeutics targeting COVID-19 and would like to collaborate, please reach out to us at [email protected].

Project Update: COVID-19 DNA Synthesis

It’s been an intense and inspiring few weeks as our DNA synthesis team, Biofab, has been working hard to produce the first batch of SARS-CoV-2 protein constructs. This week, we sent the first 288 plasmids to Addgene and BioBricks Foundation, for distribution to academic and industrial labs.

The first set of plasmids consists of SARS-CoV-2 annotated proteins in E. coli and yeast vectors, with various C-terminal tags, suitable for protein expression and purification. We expect to send more from this set to Addgene and BioBricks Foundation each week, as well as mammalian expression constructs, additional Spike protein constructs for expression and VSV pseudotyping, and plasmids containing viral DNA. Check this repository for the full set of sequences already deposited and in our synthesis queue.

You should be able to access these sequences shortly from Addgene and BioBricks Foundation. If you have questions, other ideas, or a project that you think could benefit from access to Ginkgo’s foundries, please reach out to [email protected].

Scaling Up Whole Genome Sequencing of COVID-19

UPDATE: After publishing this blog, Ginkgo has determined that our NGS machines can be used for even higher priority uses to help communities respond to COVID-19. Please note we are continuing with this viral genome sequencing work but are focusing on providing some of the scaled capabilities to these other efforts.

Scaling up the infrastructure for testing and tracking COVID-19 is one of the most important things we can do at this stage of the pandemic. Towards this broader effort, at Ginkgo we are focusing our next generation sequencing (NGS) pipeline with a target of being able to sequence 10,000 full viral genomes per day from de-identified patient samples in order to effectively track the evolution of the virus as it spreads. We’re planning to work on this with clinical labs including the CLIA-approved testing facility at Battelle and we are actively seeking other collaborations with labs generating patient RNAs for sequencing—please reach out to us at [email protected].

Current testing methods

The United States has limited capabilities to detect new pathogens such as SARS-CoV-2 coronavirus in infected individuals or environmental samples. Clinical laboratories rely on qPCR testing that reports the presence or absence of virus but provides no viral genetic sequence information.

Sequencing allows tracking of variants as the virus spreads throughout the population, enabling tracing transmission chains in time and location. Transmission chains critically inform public health control and containment measures, while knowledge of virus variability can guide the development of vaccines and cheap diagnostics.

Too few samples from infected individuals are currently being sequenced, and essentially no environmental samples are being tested. The ability to perform sequencing at enormous scale, to enable population-level testing and long-term surveillance, is needed.

With such a capability, tens of thousands of samples could be sequenced daily, including:

  • All patient-derived samples submitted to public health departments, etc.;
  • Random samples drawn from apparently well individuals; and
  • Diverse environmental samples, drawn from points of entry or transit, airplanes, trains, buses, and subways, other public places, and sewers.

Deep and broad sampling would provide data needed to determine incubation times, spread mechanisms, and prevalence, to gauge the extent of herd immunity, and to create predictive models that may guide containment efforts in this and future pandemics. As therapeutic options come available, we want to spot any emerging drug resistance or vaccine escape mutations.

Repurposing Ginkgo’s NGS pipeline

In a normal day at Ginkgo, we sequence DNA from thousands of different bacterial, fungal, and plant samples thanks to our automated sample preparation methods and terabyte-scale data de-multiplexing algorithms. These tools make it possible for us to quickly shift to sequencing up to ten thousand small viral genomes every day.

We can start from already extracted RNA from clinical labs, or use our automated sample preparation system and standard methods to extract RNA from patient samples or environmental swabs. Viral RNA would be amplified by reverse transcription using virus-specific primers (with human-specific primers serving as an internal positive control) to generate material suitable for our high-throughput NGS process. Our existing bioinformatics pipeline would be extended to quantify virus in each sample, report any failures to detect the positive control (indicating a sample which must be re-queued), and assemble the detected virus sequences and format them for submission to public and/or government databases.

We hope that this sequence data can serve public health efforts as well as the growing community of biologists and bioengineers working to track the virus and develop therapies and vaccines. Our approach would not be possible without the great open science exemplified by ARTIC Network, CDC, Nextstrain, and others. We look forward to a day very soon when we start adding to the database of publicly available viral sequences. We will be continuously looking to build the network of upstream collaborators that can generate RNA samples for analysis and ensure that our pipeline is doing the most good by sampling broadly.

Please spread the word so that we can ensure that samples which could be sequenced don’t languish in freezers, and if you are a clinical site generating patient RNAs we hope you’ll get in touch with us at [email protected] to start talking about how we can work with you.

Synthetic Biology (and beyond) Community response to COVID-19

Many organizations across biotech and synthetic biology are working hard to develop new diagnostics, vaccines, and therapeutics against COVID-19. Here is a running (non-comprehensive!) list of some of what we’ve seen so far, with a focus on these areas:

Data
Research tools
Community resources and accelerators
Diagnostics
Environmental testing
Therapeutics
Vaccines
Manufacturing and scale-up

If you are working on something you’d like to share, could use support for, or if you know of other great projects missing from this list, please email [email protected].

* * *

Data

There are many excellent resources for open public health, virology, and immunology data that are supporting efforts against COVID-19.

 

Viral biology

 

Viral tracking and evolution

  • 🧬 Ares Genetics — Next generation sequencing of virus to track evolution
  • 🧬 Nextstrain – Real time tracking of viral evolution

 

Public health tracking

 

Immune response characterization

 

Clinical trials data

 

Other data and news aggregators


Research tools

Molecules derived from the virus—nucleic acids like RNA or DNA, or proteins—are valuable tools for COVID-19 R&D, forming the basis of diagnostics as well as being essential for developing and testing new vaccines and treatments. These companies are offering antigens, antibodies, RNA, and DNA for COVID-19 research.

Research test kits — qPCR

 

Research test kits — Immunoassays

 

Nucleic acids

 

Antigens, antibodies, and enzymes

 

Software

 

Community resources and accelerators

 

Diagnostics

At this stage in the pandemic, widespread testing is essential to slowing the spread of the virus. Many organizations, from hospitals to academic labs, startups to multinationals have stepped up to develop, manufacture, and scale up testing kits. Check out the FDA’s page tracking diagnostic tests for more information and FindDx.org for an exhaustive list and this document for a detailed background on how these tests work.

Nucleic Acid Tests

 

Immunoassays

 

CRISPR based diagnostics

 

Other diagnostic tests 

  • 🌡 MiProbes — Rapid test to identify viral proteins

 

Testing hubs

 

Automation and scaling protocols

  • 🤖 Hamilton
  • 🤖 OpenCell — Scaling up testing infrastructure
  • 🤖 OpenTrons — Scale up of testing automation
  • 🤖 Salis Lab — Protocols for massively parallel testing
  • 🤖 Zymergen — Supporting automation for testing at the Chan Zuckerberg Biohub

 

Environmental testing

Testing for the presence of virus on surfaces and in other environments like sewers can help track and monitor for the spread of COVID.

 

Therapeutics

A large number of new and repurposed medicines are making their way through preclinical research and clinical trials to get to the patients that need it most. This list is biased for biologic drugs, such as antibodies, rather than small molecule therapeutics that could treat infection. Many of these therapies use antibodies, often derived from the blood plasma of patients that have recovered from coronavirus, to help the immune system of patients fight the virus directly.

Antibody therapies in development

  • 💊 AbCellera — Developing antibody therapy with Eli Lilly
  • 💊 CytoDyn — Phase 2 trial antibody therapeutic
  • 💊 Emergent BioSolutions — Plasma-derived antibody therapy
  • 💊 Kamada — Plasma derived IgG therapy
  • 💊 La Jolla Institute — Coronavirus Immunotherapy Consortium
  • 💊 Regeneron — Plasma derived antibody therapy
  • 💊 Takeda — Plasma derived IgG therapy
  • 💊 Vir — Developing antibody therapy with Bingen

 

Rapid antibody discovery

 

Other therapeutics 

 

Vaccines

In the long term, vaccines are essential for eradicating the thread of dangerous pathogens. Many groups are in the process of developing and testing several different kinds of vaccines. Vaccines train the immune system to recognize the virus so that it can be ready to clear the virus at the first sign of infection. Vaccines can be made from a number of different biological molecules: DNA, RNA, proteins, virus like particles, or live attenuated virus. Check out the WHO landscape of candidate vaccines for more.

Live attenuated virus vaccines

 

Virus-like particle (VLP) vaccines

 

Non-replicating viral vector vaccines

 

mRNA vaccines

 

DNA vaccines

 

Protein vaccines

 

Other vaccines

 

Adjuvants


Manufacturing and scale up

Once a new antiviral therapeutic or vaccine is developed and tested, it needs to be scaled up for delivery.

Other products

  • 🧼 Amyris—hand sanitizer

 

Are we missing something? Please email [email protected].

Fighting COVID-19 by Synthesizing DNA

Researchers developing novel diagnostics, therapeutics, and vaccines against COVID-19 all rely on DNA encoding viral proteins as a first step for many different kinds of important experiments. As part of our ongoing COVID-19 related work at Ginkgo, we are collaborating with researchers at Stanford University’s Department of Bioengineering and using our DNA design and synthesis capabilities to build DNA that will enable researchers to express these viral proteins—for example the “spike” protein on the surface of the virus that is the target of the vaccine currently in clinical trials, as well as being used in developing rapid point of care diagnostics and antibody-based drugs. We’ll make this DNA available for distribution to academic institutions and companies via Addgene and the BioBrick Foundation’s Freegenes project.

What we’re making

Image result for covid-19

The virus is made up of 11 open reading frames that produce 16 mature non-structural proteins, as well as 4 structural proteins making up the spike, envelope, membrane, and nucleocapsid. The sequence of the genome is available here:  NC_045512.2 version of the SARS-CoV-2 viral genome

We’ll synthesize:

  •  the DNA encoding all of these SARS-CoV-2 proteins on plasmids for expression in E. coli and S. cerevisiae, along with pull down tags (e.g. 6xHis) and T7 promoter for mRNA production
  • Viral protein sequences with the addition of watermark sequences to identify them as synthetic
  • E. coli and S. cerevisiae-codon-optimized sequences

Do you have other ideas for sequences that would help rapidly boot up R&D for COVID-19? Please reach out to [email protected].

Safety Considerations for Cloning and Distribution

The synthesis of viral genetic sequences obviously comes with risks. Work on biosecurity to protect against the synthesis and release of harmful sequences has been a major priority at Ginkgo for a long time. You can read more about many of our efforts in biosecurity on our blog, or in this article from Bloomberg.

SARS-CoV-2 is an RNA virus and we will not be working with full length viral RNA or any live virus for this project. The NIH Guideline for Research categorizes isolated Coronavirus nucleic acids in Risk Group 2, which means that the cloning of DNA from coronaviruses into nonpathogenic prokaryotic or lower eukaryotic host-vector systems must be performed under BSL-2 containment. De novo synthesis of viral protein does not use full length viral RNA or DNA as input and results in non-infectious plasmid constructs, so can be conducted under BSL-1 containment. Storage and inoculation of frozen glycerol stocks containing cDNA constructs can be performed under BSL-1 as plasmids expressing individual proteins are not infectious.

Additionally, the International Gene Synthesis Consortium, which Ginkgo is a member of, states that:

 “IGSC companies will make gene-length sequences from nCov-2019. Under U.S. regulations, these sequences are legal and safe to manufacture and a very important part of vaccine and therapeutic development. If these sequences have certain similarity to SARS or other known regulated pathogens, the synthesis company/ordering institution may need to obtain an export license for shipping across national borders. IGSC members will not provide full length synthetic virus without specific and detailed vetting of ordering entities, and will require a license from the ordering institution from the relevant governing national licensing regimes (e.g. the Federal Select Agent Program in the US).”

Distribution of SARS-CoV-2 cDNA requires recipients to have export licenses, per 1C353 and 1C351 of this document. Distributors, such as Addgene or BBF, would be ultimately responsible for documenting and enforcing this export restriction.

Distribution of Material to Academic Organizations and Companies

Ginkgo will make available any synthesized constructs free or for a nominal fee to academic organizations and companies via a third party distributor, such as Addgene or the BioBrick Foundation, under a non-restrictive material transfer agreement such as the UBMTA or the Open MTA. If you have any questions or have ideas of other sequences that would be valuable to the biotech community fighting COVID-19, please reach out to [email protected].

$25M of Free Platform Access for COVID-19 Projects

We’re inspired and heartened by the tremendous public health response to COVID-19, and recognize that a similar scale of effort is needed by the biotech community to find long-term solutions to this crisis. Former FDA commissioner Scott Gottlieb said today:

“We must get a drug and eventually vaccine. We can have treatments, antibody prophylaxis, point of care diagnostics for early detection by fall. That must be [our] focus. #COVID19 doesn’t go away. [The] [i]nitial wave will run course into summer but it’ll be back until our technology stops it.”

We’ve built our platform to enable partners across a wide range of applications to rapidly scale their R&D efforts, and we want to apply this technology today to the fight against the pandemic. To support the people building the treatments that will stop COVID-19 Ginkgo is now offering:

  • $25M of no-cost foundry work towards projects that can use Ginkgo’s platform to accelerate development of point of care diagnostics, vaccines, or therapeutics. See below for details on how our technologies might be able to support these efforts.
  • Connection to sources of funding from private and public sources. We are coordinating with people like Sam Altman and others on private funding efforts. If you are interested in funding COVID-19 work, we can connect you to vetted technical teams.
  • Rapid sharing of R&D information as it is learned among the community of academics and companies working on solutions.

If you are currently a company or academic lab that is developing a diagnostic, drug, or vaccine and are interested in leveraging Ginkgo’s infrastructure at no cost please email us at [email protected].

Details on Relevant Ginkgo Capabilities:

Ginkgo has invested ~$400M over the last 5 years to build a 100,000 sqft automated facility that is used today to support partners like Roche and Bayer with a broad range of infrastructure for biotechnology R&D. We’ve listed some examples from our discussions with companies developing solutions to COVID-19 below, to help possible partners understand our scope. We will regularly update this list as we find additional areas of leverage we can provide to those working on COVID-19.

For the manufacturing of nucleic acid-based vaccines, we could:

  • Provide process development capacity with our large bank of ambr250 fermenters for production of vaccine DNA
  • Assist in developing E. coli or alternative strains for increased production of plasmid or vaccine DNA
  • Rapidly discover and produce enzymes capable of improving downstream in vitro processing steps specific to the development of mRNA-based vaccines
  • Use our high-throughput DNA synthesis capacity to rapidly synthesize and screen many designs for vaccine discovery and optimization

To support antibody-based therapeutics development, we could:

  • Support lead optimization of promising candidate Abs, specifically using rapid DNA synthesis to generate 100s of different Ab designs and inserting these into CHO cells at a precise set of location(s) using cell lines with pre-engineered landing pads
  • Screening via virus neutralization or (lack of) antibody-dependent enhancement of infectivity leveraging rapid & high throughput screening on the Berkeley Lights Beacon (an optical microfluidics screening platform that we have in-house)

To enable point of care diagnostics, we could:

  • Rapidly discover enzymes capable of improving CRISPR/Cas-based nucleic acid diagnostics
  • Use our protein engineering pipeline to further improve key parameters such as diagnostic specificity and selectivity, limit of detection, temperature and storage stability, and overall robustness
  • Synthesize swap-in/swap-out guide RNA components for CRISPR/Cas-based devices, allowing rapid updating as new viruses need to be detected
  • Scale protein expression to rapidly optimize production of the enzymes needed for device manufacture

To provide research tools, we could:

  • Leverage our NGS platform to provide viral sequencing of ~10,000 samples per day. Environmental samples could be sequenced at our facility and we can partner with clinical labs to increase capacity for patient samples.
  • Synthesize gene length fragments of the SARS-CoV-2 virus in a variety of expression formats and distribute via plasmid repositories to vetted and licensed entities.

More generally, we hope that our capacity for large-scale sequencing, synthesis, analytics, and cell engineering can support and accelerate efforts to develop new diagnostics, biologics, or vaccines for efforts such as those listed above and beyond. We’re looking to commit every part of our platform that can make a difference over the coming months. If you bring us an opportunity that’s not a fit for Ginkgo but can be accomplished by one of our technology partners, we’ll connect you.

We want to help connect great ideas in the community with the resources they need, whether that’s funding or access to technology at Ginkgo or elsewhere, or connections to others working on similar problems. If you have a project that needs support or are looking to contribute resources or expertise to the response and want to be connected to promising efforts, please email us at [email protected].

 

Our Work on Biosecurity with IARPA

Project Update: Read about our progress on this project here!

Our mission is to make biology easier to engineer—that hasn’t changed for the ten years we’ve been building Ginkgo. The ability to read, write, and design DNA code is having profound positive impacts in medicine, agriculture, and manufacturing, from engineered cell therapies that can target a person’s cancer cells, to probiotics for plants that can reduce the need for nitrogen fertilizers, to sustainably grown materials.

We are working to unlock the enormous power of biology: its ability to grow sustainably, to process information, and adapt to changing environments. But we’re not naive to the potential risks. We understand that as it becomes easier to engineer biology, it will become easier to engineer the part of biology that’s dangerous to humans, animals, and plants—the pathogens and parasites that can infect us. Since researchers synthesized the polio virus in 2002, it has been technically possible to chemically synthesize viruses that infect humans

To date, the work done on synthesizing viruses has been intended for medical research and other peaceful purposes, but there is a concern that someone could theoretically produce a virus or other pathogen with the intent to harm. The intentional use of pathogens to harm others is abhorrent and something that I believe that we should never do under any circumstances—as a company and as human beings. The international community agrees with me on this: 180 countries including the United States are parties to the UN Biological Weapons Convention, which was first signed in 1972 and states that we are “never in any circumstance to develop, produce, stockpile, or otherwise acquire or retain: Microbial or other biological agents, or toxins…that have no justification for prophylactic, protective or other peaceful purposes.”

As the technology for synthesizing DNA code improves, groups from governments, industry, academia, and civil society have been developing frameworks for monitoring and assessing the safety and security of these new technologies. For example, we are a part of the international gene synthesis consortium, which developed standards for screening orders made to DNA synthesis companies. Our Head of Design, Patrick Boyle, was also recently on a panel convened by the National Academies of Sciences, Engineering, and Medicine to assess the risks of intentional misuse of synthetic biology.

Today we’re announcing Ginkgo’s biosecurity initiative that directly addresses some of these potential threats from engineered DNA sequences. Our current work on biosecurity focuses primarily on detecting potential threats using software that analyzes DNA sequences.

As part of IARPA’s (the Intelligence Advanced Research Projects Activity) Fun GCAT program, we are developing software to monitor DNA synthesis. This software is intended to ensure that no one orders DNA sequences that could have a pathogenic function. Think of this like a malware detector in computer programming—“programs” being written in synthetic DNA will go through the detector software, which will flag any sequences of concern before they are synthesized. The custom software we’ve developed for designing DNA sequences in our foundries is a useful start for a project like this—we need to be able to predict the function of enzymes based on their sequences in order to design new functions in our engineered microbes. Rather than predicting if an enzyme sequence could be used to produce, say, a fragrance or vitamin, here we’re applying the same types of algorithms to predict whether a given bit of code could be potentially harmful.

Unlike computer viruses, however, new biological viruses can also evolve in the wild. When a new virus emerges, researchers quickly sequence it to understand where it came from and how to best treat it and develop vaccines against it. We’re addressing this as part of another software-based biosecurity initiative, IARPA’s Finding Engineered Linked Indicators (FELIX) program. Here we are using deep learning to identify if the sequence of a new pathogen developed naturally or was engineered by humans. We’re leveraging our experience engineering the world’s largest library of engineered DNA sequences to help us train the software to detect whether something has been engineered.

Beyond developing software to guide the detection of threats, synthetic biology can also be important for responding to emerging diseases, for example making rapid response vaccines. It’s been almost a decade since the Venter institute partnered with Novartis on rapid synthetic DNA based vaccine development and the technology has been exponentially improving since then. Working alongside other companies, universities, and government agencies, we’re excited to be part of groups involved in developing tools to prevent, diagnose, and treat current and emerging diseases.

Ginkgo is the leading developer of genetic engineering tools we have an obligation to ensure that these tools are responsibly used. We are inspired by the words of Andy Weber, the former Assistant Secretary of Defense for Nuclear, Chemical & Biological Defense Programs under President Obama and a valued advisor to us here at Ginkgo on issues of biosecurity: we believe that while synthetic biology may lead to new risks, that these new tools also actually “offer the opportunity to take the global threat of biological weapons off the table.” By helping to develop software that can detect any threats before they materialize and develop the tools that can rapidly respond to emerging infectious diseases—natural or engineered—we hope to continue to drive the responsible growth of synthetic biology and realize its enormous potential for good.

For more on this story, check out Rebecca Spalding’s article in Bloomberg: “The DNA Cops Who Make Sure the World’s Deadliest Viruses Aren’t Rebuilt.