Impact case study database

Pathway to impact: from research to commercialisation

Hagan Bayley’s research in Oxford Chemistry gave rise to a key patent on the crucial original lipid bilayer (WO2008012552A1, Formation of bilayers of amphipathic molecules) that enabled the formation and furtherance of a very successful company, Oxford Nanopore Technologies (ONT), which he spun out from the University in 2005 with support from IP Group (intellectual property commercialisation company).

ONT has attracted GBP507,800,000 in investments during the REF period (GBP613,550,000 since formation) [ E1] and in December 2020 employed 600 people (headcount: 600), 4 times as many as in 1 August 2013 [ E11]. In January 2020 ONT was valued at around GBP1,700,000,000 [ E2]. It is a truly international company with headquarters at the Oxford Science Park and offices or facilities in Cambridge (UK), Shanghai, Tokyo, Singapore, San Francisco, Boston and New York. Revenues are growing rapidly (2015: GBP700,000; 2016: GBP4,500,000; 2017: GBP13,800,000; 2018: GBP32,500,00; 2019: GBP52,100,000) [ E5].

Pioneering DNA, RNA and epigenetic sequencing technology

ONT’s pioneering technology is revolutionising DNA sequencing and the emerging fields of RNA sequencing and epigenetic sequencing. The latter two in particular are crucial for our understanding of gene expression and its relationship to development, ageing and disease. The global market for next generation sequencing was valued at USD7,800,000,000 in 2019 (source: Research and Markets) and is expanding rapidly. Oxford Nanopore’s sequencing technology is opening up a range of new opportunities owing to the novel and unique properties of this wide-ranging single-molecule detection platform (rapid, low cost sequencing; direct read-out of sequence information; sequencing of ultra-long DNA strands; portable, diagnostic applications at point of care; applicability to other biomolecules).

Figure 2: Portable MinION DNA sequencer

ONT has developed a range of DNA sequencing devices for various throughput levels in different environments (e.g. core laboratories, individual research laboratories, in the field) [ E3]. The MinION sequencer, available for free alongside a USD1,000 purchase of consumables, typifies ONT’s innovative power. This portable device is the size of a mobile phone and can sequence 500 individual DNA strands asynchronously in parallel (Figure 2) with a best-in-field yield of 42Gb. It is capable of sequencing fragments of DNA of over 1 Megabase in length and tricky repetitive DNA elements and RNA molecules. The GridION can run five MinION flow cells (chips), and PromethION enables entire human genome sequencing.

A 3,200m² UK manufacturing facility at Harwell, the MinION Building, produces flow cells for ONT’s sequencing devices. The facility, opened in 2019, houses supersize clean rooms and its capacity exceeds 1,000,000 flow cells per year [ E4].

ONT's nanopore sequencing technology has impacted in many fields from zoology and microbiology, to human genetics and cancer research. The portability of the MinION has enabled it to be used for real-time sequencing of polar ocean microbes in the Arctic, and the first ever DNA sequencing in microgravity on board the International Space Station. One of the areas where it has had the most impact is in sequencing viruses to aid global public health emergencies.

Sequencing of viruses in public health emergencies

ONT’s technology has been used for the sequencing of viruses including yellow fever and swine flu. The portability of the MinION enables surveillance in the field, for example:

• Ebola virus in West Africa (2015-16): a team led by Public Health England used the MinION to establish a field laboratory in Guinea for real-time genomic surveillance of the ongoing epidemic. The data, reported to the World Health Organization (WHO), identified two lineages and showed transmission between Sierra Leonne and Guinea. After a resurgence in 2016, MinION sequencing showed that survivors could reactivate the outbreak, which led to a WHO programme of vaccination of contacts of survivors in Guinea. [ E8]

• Zika virus in Brazil (2017): the ZIBRA project, a UK-Brazil collaboration, used MinION to sequence Zika virus genomes in north-east Brazil. Results demonstrated the region was a focal point of the epidemic and played a key role in its spread within Brazil, before spreading across the Americas. [ E9]

• Nigerian Lassa fever (2018): an upsurge in cases led the Nigeria Centre for Disease Control and WHO to urgently request sequencing information. A team led by the German Center for Infection Research used MinIONs to conduct in-country, mid-outbreak viral genome sequencing. Results showed zoonotic transmission, rather than an emergent strain or extensive human-to-human transmission, was the main source. [ E10]

Sequencing of SARS-CoV-2 and development of LamPORE testing

At the onset of the coronavirus pandemic ONT sent hundreds of MinION devices to China’s Centre of Disease Control and Prevention, which allowed the first RNA sequences of SARS-CoV-2 to be recorded. This was key to identifying the strain of the coronavirus when it first appeared and important for vaccine development and understanding viral transmission and evolution [ E6]. The MinION device was used in work published as early as January 2020 which indicated person-to-person transmission of the virus through air travel [ E6]. The conclusions of the study – including to isolate patients, and trace and quarantine contacts as early as possible – helped to inform the global response to the pandemic. Surveillance of the mutating SARS-CoV-2 RNA sequence has helped to provide information about its mode and speed of evolution, geographical spread and adaptation to human hosts. Recent examples include how COVID-19 can transmit from mink to humans and back again, and how the 439K variant evades antibody-mediated immunity [ E13].

ONT acted with remarkable speed to develop COVID-19 diagnostics including LamPORE, a parallel viral RNA amplification and barcoding diagnostic protocol, which utilises rapid MinION or GridION sequencing. This 90-minute test can be carried out on-site (e.g. in hospitals). The UK government ordered 450,000 LAMP swab tests from ONT in August 2020 [ E7]. The Department of Health and Social Care (DHSC) conducted a validation study of LamPORE on 1,200 asymptomatic NHS staff and symptomatic patients who had undergone previous respiratory pathogen testing. A total of 3,966 swab and 18,435 saliva samples were tested across 4 NHS hospital sites. Results published in December 2020 show the technical performance of the LamPORE assay demonstrated a sensitivity of 99.57% and specificity of 99.40%. When the technology was evaluated in the setting of saliva samples using RNA extraction, the sensitivity is 98.94% and specificity 99.39% across all samples tested [ E14].

The DHSC report concludes that 'the key advantage of LamPORE, as part of a testing regime for both saliva and swabs, is its capability to offer high throughput testing of SARS-CoV-2 for both asymptomatic or symptomatic testing... The LamPORE assay in the RNA mode has been successfully applied in this use case to populations of healthcare workers with the aim of curtailing transmission between staff and to patients within healthcare settings. The NHS asymptomatic staff saliva testing pilot successfully facilitated daily on-site testing as an additional test to support SARS-CoV-2 detection' [ E14].

The DHSC Minister for Innovation said of the report: ‘With one in three people not displaying symptoms of Covid-19, broadening asymptomatic testing is critical to protect those at highest risk. Oxford Nanopore’s LamPORE test is another example of British innovation leading the way, and is an incredibly useful addition to our Covid-19 testing toolkit – delivering accurate results to people with and without symptoms’ [ E12]. The LamPORE assay is being expanded to encompass other respiratory infections such as Influenza and Respiratory Syncytial Virus (RSV), crucial in the winter months.

Nanopore sequencing has been of paramount importance in the global response to the COVID-19 pandemic and ONT continues to develop yet more technological advances backed by the company’s intense R&D programme and large IP portfolio, including 7 patents arising from Bayley’s work at Oxford during the REF period. Developments include the SmidgION (a smartphone attachment), the smallest sequencing device ever developed, and the Plongle, which offers high-throughput, real-time sequencing in a 96-well plate format, compatible with automation.