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Gene Expression Profiling Company BioSpyder Enters Spatial Sequencing Market

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SAN FRANCISCO (GenomeWeb) – BioSpyder, a Carlsbad, California-based company that has focused on providing gene expression profiling services, primarily in the toxicology space, has moved into the nascent but growing spatial RNA sequencing market.

The company was founded in 2011 with the goal of developing sample prep technologies for next-generation sequencing that would reduce cost and increase efficiency. Joel McComb, founder and CEO at BioSpyder, said that the firm has specifically targeted high-throughput customers, which is how it came to focus on the toxicology space. BioSpyder's flagship product is TempoSeq, a targeted RNA sequencing technology that it launched as both a kit and service last year.

The technology involves barcoding and sequencing short fragments of each transcript in order to pool thousands of samples in one sequencing run. The firm has developed a set of detector oligos that all have the same primer landing site but target a different transcript region. These oligos, which are 25 bases in length, are ligated directly onto the mRNA molecule, with two detector oligos per gene. The molecules are then PCR amplified with barcodes and sequencing adapters, followed by pooling and sequencing. TempoSeq acts essentially as a counting technology, determining the relative expression levels of the targeted genes.

There are two main advantages of the method, McComb said. It does not rely on converting RNA to cDNA and it can be very high throughput because it targets just a small region of any given gene. Upwards of 5,000 samples can be pooled and sequenced in one run. The method is quantitative, counting the number of transcripts to determine expression levels, but since it only sequences 50 bases of an mRNA, it is not suited for studies that require full-length transcript sequencing.

The TempoSeq assay can be run on a cell culture lysate, said Harper VanSteenhouse, BioSpyder's director of technology integration. "The assay goes straight into [the lysate], you don't have to purify nucleic acids," he said, which makes it appealing for toxicologists who want to run a 384-well plate "straight from cell culture that's been dosed with a compound," he said.

BioSpyder then expanded the technology to enable it to run on a fixed sample, which involves scraping a bit of the tissue sample from the slide and running it in a tube. Company researchers have described the TempoSeq technology from cell culture lysate and fixed tissues in publications in PLOS One.

When the company sought to expand on the technology, the researchers' goal was to make it amenable to pathologists who "want to look at a slide and pull off transcriptomic information that is tied to a spatial position," VanSteenhouse said.

In its move into the spatial transcriptomics space, the BioSpyder team adapted its TempoSeq technology to work in situ on fixed tissue. Similar to other spatial sequencing technologies, BioSpyder's CellSensus technology starts with a pathology slide and performs the TempoSeq chemistry directly on the slide. A slide is infused with the TempoSeq probes and fluorescently stained. It is then digitally imaged and users select their region of interest. hey then remove the probes, which also include dual indices encoding spatial information, from that specific region, followed by amplification, pooling, and sequencing. CellSensus has a spatial resolution down to 20 microns.

Company researchers presented the technology in a poster at the American Association for Cancer Research annual meeting last week.

VanSteenhouse said the company is now offering its CellSensus technology as a service and is targeting pharmaceutical companies as initial customers. In addition, he said, the firm is developing instrumentation for customers to run the CellSensus assay in their own labs. The instrument would be an add-on to a researcher's existing microscope that would enable aspiration and dispensing of the probes, he explained.

McComb declined to disclose pricing information for the technology, noting that it is project-driven and so varies for each customer, but he said that the company's goal is to be cost competitive.

While the market for spatial 'omics technologies is still nascent, it is growing rapidly. Established companies such as NanoString Technologies and 10x Genomics are developing products for the space and other startups have developed their own solutions. McComb said one advantage of BioSpyder's technology is that even when the firm does launch a CellSensus kit, there will not be expensive instrumentation associated with it, just a device that is added to existing pathology lab microscopes, so it should integrate well with standard workflows.

Going forward, McComb said that BioSpyder would consider spinning off its spatial gene expression company. Already, it has spun off another company, BioClavis, that is focused on molecular diagnostics. "The goal is to have [BioSpyder] be an incubator and spin off companies to focus on specific market segments," he said. "If we get to a point where there are [spatial profiling] applications that really deserve a focused, concerted effort, we would spin it off," he said. 

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