NEW YORK – Precision oncology firm AccuraGen is eyeing the minimal residual disease (MRD) testing market with a whole-genome sequencing (WGS) liquid biopsy assay, which promises to deliver high sensitivity, specificity, and a fast turnaround time.
The San Jose, California-based company recently published a peer-reviewed study demonstrating the feasibility and utility of its assay, which it developed in-house and hopes to offer as a clinical service in 2026.
Dubbed AccuScan, AccuraGen's MRD test is a tumor-informed WGS assay that analyzes a patient's circulating tumor DNA but does not require bespoke reagents, said Li Weng, AccuraGen's senior VP of R&D.
As part of the AccuScan workflow, cell-free DNA (cfDNA) is isolated from a patient's posttreatment plasma sample and is subsequently denatured and circularized through intramolecular ligation. After that, the circularized DNA molecules undergo rolling circle amplification, generating concatemers that contain tandem copies of the template molecules. The concatemers are then sequenced and aligned to the human reference genome.
Meanwhile, a patient's tumor tissue is also analyzed using WGS to inform patient-specific mutations. Together with the tumor sequences, the cfDNA mutational profile is processed by AccuScan's analysis pipeline to help determine a patient's MRD status.
According to Weng, there are a few advantages to the AccuScan assay. For one, she said the workflow's intramolecular ligation step is "very efficient," allowing the assay to accommodate samples with a low DNA input. Additionally, unlike conventional PCR, AccuScan's rolling circle amplification step does not propagate errors, she said. This allows the assay to achieve error suppression by only analyzing true mutations, which are present on all repeat elements of a concatemer.
Moreover, Weng noted that rolling circle-amplified WGS libraries can also be harnessed for targeted sequencing, allowing users to revisit the samples for therapy target selection or drug resistance testing after a patient is deemed MRD-positive by AccuScan.
Last month, AccuraGen researchers and their collaborators from the US and China published a study in EMBO Molecular Medicine to demonstrate AccuScan's performance. In the study, they applied the assay to a total of 117 plasma samples from 57 cancer patients, including 32 with colorectal cancer (CRC), 17 with esophageal squamous cell carcinoma (ESCC), and eight with melanoma. The CRC and ESCC samples were collected from hospitals in Shanghai, while the melanoma samples were obtained from the Yale School of Medicine.
Overall, the study noted that AccuScan has "a high success rate" in handling cfDNA samples across a wide range of input amounts, with the lowest sample input being less than 5 ng. Additionally, the study authors concluded that the test can achieve genome-wide error correction at a single read level, enabling an ultralow limit of detection down to the parts-per-million (PPM) range in analytical studies.
When applied to MRD detection, AccuScan achieved 90 percent sensitivity, 100 percent specificity, and 96.3 percent accuracy in plasma samples collected from CRC patients within six weeks after surgery. For ESCC patients, AccuScan achieved 67 percent sensitivity, 100 percent specificity, and 82.4 percent accuracy using plasma samples collected within one week after surgery.
The researchers also explored AccuScan's utility for immunotherapy monitoring using 22 plasma samples from eight melanoma patients with advanced melanoma. There, the study authors concluded that AccuScan's results showed "strong correlations" with clinical outcomes.
"To me, it was quite impressive [to see AccuScan's] sensitivity, specificity, and the low amount of starting material [required]," said Marcus Bosenberg, director of the Yale Center for Immuno-Oncology, a coauthor on the paper, and a collaborator of AccuraGen.
Because AccuScan does not involve building patient-specific regents, another advantage of the assay is the faster turnaround time, said Qin Yan, a professor of pathology at Yale and another collaborator of AccuraGen. According to Weng, the current turnaround time for AccuScan, from sample to report, is about two weeks.
With the proof of concept, Weng said AccuraGen is now working to commercialize AccuScan as a research-use-only service for basic and translational researchers beginning in the second half of 2025.
More importantly, the company plans to develop AccuScan into a laboratory-developed test, which it hopes to offer as a service to oncologists and pharmaceutical companies in the US in early 2026. To achieve that, Weng said AccuraGen is focusing on seeking strategic partners who are already operating clinical labs in hopes of bringing the technology to the market sooner, but the company could also build its own clinical lab.
Weng said the company is also interested in eventually developing AccuScan into kitted products, given that the technology can be more easily scalable and distributable without the need for personalized reagents.
To make the assay more economical, AccuScan is currently optimized for Complete Genomics' DNBSeq platform, which deems to have a per-GB lower cost than many other sequencing platforms, Weng said, though she did not disclose a specific price tag for the test. However, she noted that the AccuScan technology is fundamentally sequencer-agnostic, and the company has evaluated the assay on Illumina and Element Biosciences sequencers with "comparable" results.
Established about a decade ago, AccuraGen initially focused on developing targeted sequencing technologies for liquid biopsy treatment selection and cancer early detection products with an emphasis on the Chinese market, Weng said. Since 2022, the company has shifted its focus to developing the AccuScan technology, as part of its pivot to become a clinical service provider focusing on the US market, she noted.
The company has been financially supported by private investors including from Decheng Capital since 2016, and some non-dilutive funding, Weng said, adding that the company is seeking additional funding in the US to fuel the commercialization of AccuScan.