NEW YORK – Biotech startup Mutagentech is betting on making headway in the somatic variant analysis market with error-reducing library preparation technologies that it promises to be accurate, scalable, and cost-effective.
The New York City-based company, which is a subsidiary of human longevity-focused startup Matter Bio, has licensed methods from the Albert Einstein College of Medicine for profiling mutations in normal cells and tissues and is currently offering these assays to researchers and industry customers as a service.
To receive Mutagentech's service, customers supply samples to the company, which will perform library preparation, sequencing, and analysis for them.
According to Mutagentech Cofounder and CEO Chris Bradley, the company's service is compatible with almost all sample types that have an existing reference database, except for fixed tissues, as their chemical treatment may introduce additional mutations, making it challenging to determine the original mutational profile.
One of the core technologies underpinning Mutagentech's offerings is the so-called single-molecule mutation sequencing (SMM-seq) assay developed by the company's academic cofounders, Alexander Maslov and Jan Vijg, who are also Albert Einstein professors.
A two-step library preparation protocol, SMM-seq, which was delineated in a Science Advances paper last year, is a variation of duplex sequencing that employs rolling circle amplification to generate independent copies of each strand of the DNA to help detect and quantify ultrarare point mutations in normal cells and tissues.
After SMM-seq library prep, samples are dispatched to Mutagentech's third-party contractors for sequencing, which is primarily done using the Illumina NovaSeq X Plus platform, Bradley noted. While the company has optimized its workflows based on short-read sequencing, they are fundamentally platform-agnostic and can be carried out by long-read sequencers, as well, he added.
After sequencing, the data are analyzed by Mutagentech's in-house informatics team. Depending on the customers' needs, the company can generate a summary report of the results or return all analysis files and raw data to the clients, Bradley said.
In addition to SMM-seq, which is for somatic single-nucleotide variant analysis, Mutagentech has also licensed Single-Molecule Mutation Sequencing for Structural Variants (SMM-SV-seq), a more recent method developed by Maslov, Vijg, and their collaborators for somatic structural variant profiling.
Described in a BioRxiv preprint published last month, SMM-SV-seq builds on SMM-seq DNA but employs Tn5-mediated DNA fragmentation and tagmentation to generate more stringent ligation conditions, minimizing sequencing artifacts that may be indistinguishable from true somatic structural variants.
"For single-molecule sequencing, you have to put adapters, but there's always a very tiny fraction of the DNA fragments that ligate to each other," creating artifacts that resemble true structural variants, said Vijg. "Because somatic structural mutation frequency is very low, that can be a major problem for us."
Given that it has been previously challenging to study somatic structural variants, Bradley said the company is "very excited" for SMM-SV-seq to be published in peer-reviewed journals down the road and further validated. "It is early [days] for this particular assay, but it fills a niche that people have not had access to," he said.
With the somatic analysis technologies, Bradley said the target customers for the company are basic and translational academic researchers as well as people from the genetic toxicology space. "You can give us a set of cells that have been exposed to a compound, and we can then tell you [if] the mutation rate goes up or [if] the signature of mutation changes," he noted.
To that end, Bradley said the company's technology not only can provide a more quantifiable readout than the traditional bacteria culture-based Ames assay but also is cheaper than the animal-based in vivo mutagenicity and toxicity screening methods.
Bradley said the company has made its service "very affordable" to help drive volume. "I want us to do well because we have massive volume," he said. "Our profit comes from volume."
He declined to disclose an exact price point, however, other than noting that the company charges a flat price for its assays in the "single-digit thousands," inclusive of all costs from sample to report.
As for the turnaround time, Bradley said currently the company can return results to customers from raw samples within four to five weeks.
Besides being offered to external customers, Bradley said Mutagentech's technologies are also enabling the scientific explorations of its parent company Matter Bio for studying mutations implicated in aging, cancer, and other human diseases. That said, while Mutagentech's services are currently for research use only, there is a potential for the methods to be further validated and applied for clinical use.
Mutagentech is not the only player eyeing the somatic variant analysis market. Seattle-based TwinStrand Biosciences, for instance, has commercialized an error-correcting duplex sequencing technology for detecting rare somatic variants in various applications, including genetic toxicology research.
Incorporated in late 2022, Mutagentech has mostly been funded through the revenues it has generated, and the company is currently cash-flow positive, Bradley said. So far, its parent company Matter Bio has raised $7 million in investments, including $5 million in dilutive funding and $2 million in grants, Bradley noted, adding that the funds are distributed among its subsidiaries.