Skip to main content
Premium Trial:

Request an Annual Quote

Enzymatics' Archer Targeted Sequencing Tech Enables Cancer Gene Fusion Analysis, Custom Assays

Premium

Reagent provider Enzymatics has commercialized a new targeted sequencing technology that allows customers to detect cancer-relevant gene fusions from RNA, and has plans to offer additional catalog and custom assays to study fusion transcripts as well as DNA variants.

The technology, which is based on anchored multiplex PCR (AMP), was originally developed by ArcherDx, a startup that Enzymatics acquired last summer for up to $50 million in cash, equity, and milestone payments. Enzymatics, based in Beverly, Mass., sells the new reagent kits to both research and clinical laboratories under the Archer brand.

The AMP method was invented by three clinical researchers − John Iafrate, Long Phi Le, and Zongli Zheng − at Massachusetts General Hospital. Their original goal was to develop an alternative to fluorescent in situ hybridization to study gene fusions in formalin-fixed paraffin-embedded lung cancer samples.

ArcherDx, which was founded early last year and was based in Boulder, Colo., obtained an exclusive license to the patent-pending technology from MGH, both for the production and sale of kits and for offering it as a service.

One of the AMP method's distinguishing features is the use of one target-specific primer and one common primer, which binds to an adapter that is ligated to one end of the DNA.

In a gene fusion assay, this allows researchers to find both known and novel fusion partners "in a very simplistic way," Jason Myers, Enzymatics' CSO, told In Sequence. Myers used to be ArcherDx's CEO and is one of the firm's co-founders.

The use of only one target-specific primer also makes the method very suitable for analyzing fragmented DNA and RNA, such as from FFPE samples, he said. Methods that require two target-specific primers, on the other hand, may run into trouble with such degraded samples.

The AMP workflow has seven steps and requires at least 1 nanogram of total nucleic acid for the gene fusion assay, extracted from FFPE samples, fresh-frozen tissue, or blood, though the company recommends 20 nanograms to increase library diversity. For RNA analysis, it starts with the conversion of RNA into cDNA. For both RNA and DNA analysis, next steps are the ligation of barcoded adapters and two rounds of PCR, resulting in a sequencing-ready library that is compatible with either Illumina or Ion Torrent platforms.

The process takes about seven hours for RNA, with less than two hours of total hands-on time. For DNA, it requires about four hours, with less than one hour of hands-on time.

Enzymatics provides the reagents for each step in lyophilized form, rather than in solution, which simplifies the workflow by reducing the number of pipetting steps. Myers said this minimizes mixing errors, reduces the potential for contamination, and saves time. In addition, lyophilized reagents can better tolerate temperature changes during shipment.

Along with the reagents, the company offers a web-based analysis pipeline where customers can analyze their sequence data for mutations in the target.

A description of the method is expected to be published in a scientific journal within the next several months, Myers said.

Last month, Enzymatics launched its first Archer product, a kit to detect gene fusion transcripts involving the ALK, RET, or ROS1 genes, which are of particular interest in lung cancer. "Pharmaceutical companies are very interested in those genes," Myers said. "As a small introductory panel, that was ideal."

Enzymatics sells the Archer ALK/RET/ROS1 fusion detection kit in two versions – for use with the Illumina MiSeq or for Ion Torrent sequencing. Each kit has a list price of $1,595 and provides reagents for up to eight samples.

This spring, Enzymatics plans to launch three more gene fusion panels for sarcomas, hematological cancers, and carcinomas. In addition, cancer researchers will be able to order custom gene fusion assays starting later this month, using primer design software provided by Enzymatics.

The company also plans to offer custom assays for the targeted analysis of DNA this spring, including copy number variants, single nucleotide variants, and insertions and deletions, as well as an assay for RNA abundance analysis. According to Myers, the method can currently handle up to 600 different targets in a single tube, but internal experiments suggest that number could increase to several thousand targets.

By the end of the year, Enzymatics also wants to launch Archer assays that can handle both RNA and DNA simultaneously, he added.

Longer term, the firm is interested in developing a US Food and Drug Administration-approved kit for diagnostic use of the technology. "We do have great interest in that and have been talking to potential strategic partners about that, but we don't have any detailed plans yet," Myers said.

He said the AMP technology provides advantages over other targeted sequencing methods. It requires less input DNA than Illumina's TruSeq, for example, and a lot less than hybridization-based capture methods. Also, it can amplify more targets in the same tube than most AmpliSeq custom assays, he added.

Enzymatics is targeting cancer research centers, pharmaceutical companies, contract research organizations, and academic research labs with the Archer assays. So far, it has had several collaborators and beta customers, including the Broad Institute, MGH, and the MD Anderson Cancer Center.

While the company sells its gene fusion kit for research use only, "we see people on the path to develop it themselves into a lab-developed test" as an alternative to FISH, Myers said. The inventors of the AMP method, for example, launched a clinical assay for fusion transcript detection at MGH's Center for Integrated Diagnostics last summer, following an internal validation.

The Broad Institute has tested the technology in a pilot project to rapidly characterize fusion transcripts in leukemia samples. "We are interested in further evaluation of the Archer technology, not just for RNA fusion detection but also possibly for DNA targeting of small numbers of genes or exons," Niall Lennon, director of technology development for the Broad's genomics platform, told IS. "The ability of the method to multiplex designs and to come to the lab as a lyophilized reagent with minimal hands-on steps is of particular interest and should be a great benefit should we decide to move one of these assays to our clinical lab."

The Scan

WHO Seeks Booster Pause

According to CNN, the World Health Organization is calling for a moratorium on administering SARS-CoV-2 vaccine boosters until more of the world has received initial doses.

For Those Long Legs

With its genome sequence and subsequent RNAi analyses, researchers have examined the genes that give long legs to daddy longlegs, New Scientist says.

September Plans

The New York Times reports that the US Food and Drug Administration is aiming for early September for full approval of the Pfizer-BioNTech SARS-CoV-2 vaccine.

Nucleic Acids Research Papers on Targeting DNA Damage Response, TSMiner, VarSAn

In Nucleic Acids Research this week: genetic changes affecting DNA damage response inhibitor response, "time-series miner" approach, and more.