AirSeq, rapid DNA air sequencing for biological threat detection and monitoring

AuthorAuthor

Jannic Meyer & Jack Wang
August 15, 2024

Welcome 🇪🇺

The Covid19 pandemic showed us painfully that detection and protection from biological threats is still in its infancy. This is where AirSeq comes in to play. What is that, you might ask? Well you are about to find out!

Detecting infectious agents that are of airborne nature is a challenge. AirSeq uses DNA sequencing to provide early warning of airborne pathogens. This can lead to better biosecurity measures to prevent, detect, and respond to biological threats as early as possible should they emerge.

Our guest authors Simon Kim, Dr Matthew Clark and Dr Richard Leggett explain how the technology can be used for dual-use purposes in commercial applications such as environmental monitoring, veterinary and crop pest management, as well as governmental use cases like biosecurity and pandemic control.

Yours,
Uwe, Jack and Jannic

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AirSeq, rapid DNA air sequencing for biological threat detection and monitoring

In 2013 Professor Matt Clark of the Natural History Museum and Dr Richard Leggett of the Earlham Institute started researching a common pain point in the agricultural industry. This was the prevalence of airborne fungal pathogens that attacked major crops such as wheat, rice, maize and potato. Given the challenge of detecting infectious agents that are of airborne nature, the scientists began working on a comprehensive solution to detect a range of pathogens in the air, to do it agnostically, and by capturing their genetics.

Their primary efforts in this pursuit involved a non-pathogen specific approach. This contrasts with how most researchers generate sequence for a just single gene fragment from environmental samples. Achieving this entailed the development of novel molecular biology methods and bespoke bioinformatics to sequence and accurately classify the DNA of organisms found in air samples. But why DNA? DNA (Deoxyribonucleic acid) is a microscopic molecule found within every cell of every living organism. It carries the unique identity or genetic blueprint specific to that organism and is therefore ideal for sequencing and identifying pathogenic cells that exist in our environment. The combination of technologies based on this concept was subsequently named ‘AirSeq’.

Over the following years, the team’s journey in developing this viable solution involved several proof-of-concept tests to validate the efficacy of the technology. One key trial involved a controlled wind tunnel experiment to measure the detection ability of the AirSeq pipeline. Increased amounts of Bacillus thuringiensis spores (very strong bacteria like anthrax from which it is difficult to acquire DNA) from 0-3 million were released into an enclosed wind tunnel structure 5 metres from the air collector over 10 minutes. The outcome of this saw a proportional increase in the numbers of spores detected, and very reproducible results by AirSeq – a success which greenlighted further testing in real-world contexts.

Figure A. AirSeq performance in a wind tunnel experiment while releasing B. thuringiensis spores

AirSeq workflow: air is filtered for a defined time period through a liquid collection buffer reservoir. After sampling the liquid collection buffer is concentrated, the eDNA extracted from the sample and a whole-genome shotgun library prepared using a low-input DNA compatible Illumina Nextera protocol. After library preparation the sample is ready for sequencing and data analysis [1].

2019 proved to be a turning point when significant leaps were made in the R&D progress. With an external corporate partner, the AirSeq team participated in the SIGMA+ Biosensors project, run by DARPA (Defence Advanced Research Projects Agency) in the US to monitor airborne human pathogens. DARPA seeks to create breakthrough technologies and capabilities to secure national security for the US and its allies [2]. With DARPA’s support and involvement, the team significantly boosted AirSeq's capabilities, allowing it to:

  • Achieve much higher DNA yields per volume of air

  • Reach a pathogen detection false positive rate of less than <1 in 10-7

  • Reduce the time to extract, amplify and sequence DNA to under 90 minutes

  • Require smaller samples to run tests with

  • Produce a pipeline suitable for automation

  • Develop an RNA pipeline able to detect and classify airborne viral sequences

With these advancements the AirSeq technology expanded its potential for national security defence applications such as biosecurity and pandemic readiness.

With 1 in 8 deaths worldwide being linked to bacterial infections alone in 2019 [3], it became apparent that a comprehensive biological threat defence strategy was needed. But it was the COVID-19 global pandemic and a rapidly changing geopolitical landscape that heightened the awareness of biothreats and stressed the importance of developing advanced near real-time biosurveillance capabilities. A “biothreat” can be any biological agent or organism that causes harm to human, animal, or plant health [4]. The indirect costs of biothreats, as seen with COVID-19, can be expensive, including disruption of economic output and strain on healthcare infrastructures. As of 2024, the World Health Organisation estimates the global death toll from COVID-19 to be over 7 million [5], whereas the IMF forecasts a US$ 12.5 trillion loss to the global economy[6].

Stark data like this has prompted major Western nations to launch preventative biosecurity initiatives to prepare against biological threats. In 2022, the US Government launched the National Biodefense Strategy for Countering Biological Threats and Enhancing Pandemic Preparedness. And in 2023, the UK Government launched the Biological Security Strategy (BSS) to monitor threats and risks. Also in 2023, NATO set up an RTG (Research Task Group) for Sequencing for Environmental Aerosol Background Monitoring. Prof Clark and Dr Leggett have been appointed as UK panel members to the now 14 member states strong group.

With the UK government’s new Biological Security Strategy, the goal now is to prevent, detect, and respond to biological threats as early as possible should they emerge to threaten the UK and its interests [7]. This strategy includes the launch of a real-time biological threat radar of which the establishment of a National Biosurveillance Network (NBN) is key. However, the current biosurveillance landscape contains gaps. For example, surveillance is often captured in a non-real-time manner which limits a proactive response [8]. Current technologies can only identify a limited number of pathogens, restricting its capacity to detect both known and emerging threats. Other gaps include current surveillance capabilities at UK borders and the inability to detect deliberate or accidental release of pathogens [8]. The AirSeq technology is well positioned to address these gaps.

Today AirSeq is at the end of its current technology development phase. Projects such as DARPA SIGMA+ have involved the use of innovative methods for tracking variance in air microbiomes across different geographical ecosystems. Hundreds of AirSeq samplings across urban and rural sites have been conducted as part of this process as well. With the core technology (patented novel molecular biology methods and bioinformatics platform) prototyped, tried and tested, AirSeq is now being offered as a service in the UK. The service includes air collection, lab-based DNA extraction and sequencing, as well as bioinformatics analysis and web-based visualisation of results. Upon receipt of the air samples, the sequencing results can be made available in under 90 minutes.

The next technology development phase envisages the integration of air collection and DNA sequencing into a portable, automated device that delivers results via a secure cloud interface. The product development is a multi-year project scheduled to start this year.

Going forward there are plans to spin out the AirSeq technology into a dual-use venture with both national security and civil applications. The venture will use AirSeq for biosecurity and pandemic readiness applications on the one hand but will also develop use cases such as environmental monitoring, veterinary and crop pest management, and indoor air quality monitoring on the other.

In light of the ever-changing landscape of biological challenges that range from emerging infectious diseases to bioterrorism threats, the demand for preparedness in the form of robust biosecurity measures is being realised rapidly and on an international scale. The AirSeq technology represents a new disruptive technology in the fields of biosurveillance and biosecurity, with its capacity to transform the identification and surveillance of biological threats. It offers tremendous potential in safeguarding the wellbeing of our environment and its diverse inhabitants, while also strengthening global security measures.

Simon Kim, Entrepreneur in Residence, Natural History Museum [email protected]

Dr Matthew Clark, Genomics Research Leader, Natural History Museum [email protected]

Dr Richard Leggett, Group Leader, Earlham Institute [email protected]

References:

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European Resilience Tech Newsletter Team

Uwe Horstmann co-founded Project A Ventures in 2012 as General Partner and has built Project A to be a leading European early stage investor with over $1bn USD under management and having backed 100+ founders. In addition to Project A, Uwe serves as Reserve Officer in the German armed forces and advises the German Ministry of Defence in digital transformation issues.

Jack Wang is a software engineer turned product driven tech investor and joined Project A in 2021 to lead the firm’s deep tech investing, which have grown to include DefenceTech. Prior to joining Project A, Jack worked in a variety of organisations such as Amazon and Macquarie Group across Australia, US and UK / Europe. Jack holds a MBA from London Business School and Bachelors of Engineering (Bioinformatics, 1st) from UNSW, Australia.

Jannic Meyer joined Project A initially contributing to what is now known as the Project A Studio, partnering with founders at the pre-idea stage, where he covered a variety of topics ranging from energy infrastructure to dual-use robotics and led our investment in ARX Robotics. He is now part of the investment team at Project A covering all things resilience.

Project A Ventures is one of the leading early-stage tech investors in Europe with offices in Berlin and London. In addition to 1 billion USD assets under management, Project A supports its 100+ portfolio companies with a platform team over 140 functional experts in key areas such as software and product development, business intelligence, brand, design, marketing, sales and recruiting. Project A have backed founders of Trade Republic, WorldRemit, Sennder, KRY, Spryker, Catawiki, Unmind and Voi as well as founders building in European Resilience: