Research collaboration has resulted in new ‘liquid biopsy’ research workflow using nanopore sequencing to detect molecules that are associated with cancer, circulating in blood
Oxford Nanopore Technologies and Dutch start-up Cyclomics today announced the ‘developer access’ of a new research workflow: the world’s first nanopore sequencing-based solution for ultra-sensitive detection of circulating tumour DNA (ctDNA).
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The method works by detecting and analysing cell-free DNA (cfDNA) in the blood stream. In the context of cancer, tumours release DNA as their cells die; if specific mutations are present in the DNA of those tumour cells, those mutations can be found in the ctDNA. The detection of ctDNA has historically been challenging as a very low percentage of the cfDNA in the blood typically originates from the tumour.
To address this challenge, Cyclomics developed CyclomicsSeq, a novel ctDNA and cfDNA detection and analysis method that leverages nanopore technology to deliver fast and low-cost sequencing with the potential to be deployed at the point of care. CyclomicsSeq ensures that individual ctDNA molecules present in blood can be sequenced - with near 100% accuracy for TP53 as shown in a clinical study - allowing for indirect detection of a specific tumour from a blood draw. CyclomicsSeq uses nanopore technology’s ability to sequence any-length fragment of DNA, to target the ctDNA and cfDNA in the 200base pair range. CyclomicsSeq can also be used on any Oxford Nanopore device, therefore no new equipment is necessary to perform highly accurate analyses.
In this proof-of-concept study published in NPJ Genomic Medicine, the team demonstrated that a specific CyclomicsSeq assay for TP53, a tumour-suppressor gene with a mutational profile that may serve as an indicator for tumour presence, could be used to successfully monitor tumour burden during treatment for head-and-neck cancer patients. They were able to facilitate the detection of mutations at frequencies down to 0.02% and the entire workflow took around 3 days — significantly less than current approaches to detect mutations in ctDNA.
Building on this early success, Oxford Nanopore and Cyclomics entered a multi-year research collaboration and licensing agreement to fine-tune the method with the goal of enabling robust detection of rare mutations that are present at below 0.5% in cfDNA. Further optimisations, including the detection of methylation – which provides critical information on cancer and can be elucidated in real time using nanopore sequencing - are now underway.
A first universal version of the CyclomicsSeq workflow, which includes library prep and analysis, is now being trialled with select users in a developer access programme. An open early access programme will follow in the coming months.
Cyclomics and Oxford Nanopore are also initiating multiple clinical research studies, including with Erasmus Medical Center in The Netherlands and other institutions to assess the clinical utility of their sequencing solution, including the clinical benefit of quick turnaround gained by not having to wait to batch samples.
Cyclomics is a spin-off from University Medical Center Utrecht, founded in 2018. They have obtained initial funding through the Oncode Bridge Fund and announced the completion of a seed funding round this month.
Gordon Sanghera, CEO, Oxford Nanopore Technologies, commented:
“We are excited to partner with Cyclomics to increase access to accurate and fast detection of cancer using nanopore sequencing. Monitoring recurring cancer today involves time-consuming, invasive scans and tests – many of which are expensive and stressful. We are proud to introduce a new method that could signal a paradigm shift in cancer detection and management by enabling healthcare providers to detect recurring cancer, with nearly 100% accuracy in the case of TP53 in the Cyclomics study, through only a blood draw. Although we’re still in the research stage of deploying this technology, we’re optimistic about what this could mean for the future of cancer and patient care.”
Jeroen de Ridder, Co-founder, Cyclomics, commented:
“Ever since we started using nanopore sequencing for genomics research at our academic labs, we were thrilled by the real-time nature and accessibility of the technology. We soon realised the potential of nanopore sequencing for developing novel assays for detection of disease mutations, particularly in the context of cancer. The CyclomicsSeq technology enables highly accurate sequencing of single cancer DNA molecules in the blood stream of any cancer patient. In the last year we have worked hard to integrate CyclomicsSeq with nanopore sequencing workflows as part of our partnership with Oxford Nanopore Technologies. In the coming years, together with the Oxford Nanopore team, we will further expand the CyclomicsSeq platform and broaden its applicability to other cancers.”
Bianca Mostert, Oncologist at Erasmus Medical Center, commented:
“Accurate low frequency variant calling from cfDNA has the potential to improve on current clinical response evaluation after neoadjuvant chemoradiation in oesophageal cancer. CyclomicsSeq offers a very promising solution for this purpose and we are looking forward to evaluating it”.
About Oxford Nanopore Technologies
Oxford Nanopore Technologies’ goal is to bring the widest benefits to society through enabling the analysis of anything, by anyone, anywhere. The company has developed a new generation of nanopore-based sensing technology for real-time, high-performance, accessible and scalable analysis of DNA and RNA. The technology is used in more than 120 countries to understand the biology of humans and diseases such as cancer, plants, animals, bacteria, viruses and whole environments. Oxford Nanopore Technologies products are intended for molecular biology applications and are not intended for diagnostic purposes. www.nanoporetech.com
Forward-looking statements
This announcement contains certain forward-looking statements. Phrases such as "potential", “expect”, "intend", “believe we can”, “working to”, "anticipate", "when validated", and similar expressions of a future or forward-looking nature should also be considered forward-looking statements. Forward-looking statements address our expected future business, and by definition address matters that are, to different degrees, uncertain and may involve factors beyond our control.
About Cyclomics
Cyclomics is a Dutch startup company founded as a spin-off from the University Medical Center Utrecht. Its ambition is to transform cancer care by enabling faster and more reliable diagnoses, particularly in the context of cancer recurrence and treatment monitoring, leveraging its proprietary circulating tumor DNA (ctDNA) detection technology CyclomicsSeq. The technology is the first ctDNA detection approach that builds on single-molecule real-time nanopore sequencing. CyclomicsSeq is currently being evaluated in clinical studies for head and neck cancer and esophageal cancer.
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