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Karolinska Spinout Xpress Genomics Fine-Tunes RNA-seq Services as Partner MGI Preps Products

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NEW YORK – A Swedish single-cell RNA-sequencing startup called Xpress Genomics has attracted enough interest that it intends to add new applications to its menu and bring in more personnel to handle both R&D ventures and manage demand for its services.

The Stockholm-based company spun out of the Karolinska Institute in 2022 to provide more efficient next-generation sequencing services with an initial focus on automated RNA-seq assays.

The company has developed an automation-friendly, full-length single-cell RNA-seq method called Xpress-seq. This technology is the basis of a collaboration with MGI of Shenzhen, China, which could launch products based on the method this year.

CEO Christoph Ziegenhain, also an assistant professor at Karolinska, founded the company with Rickard Sandberg, a professor at Karolinska who leads a laboratory focused on single-cell genomics, and Michael Hagemann-Jensen, a postdoc in Sandberg's lab.

According to Ziegenhain, Xpress Genomics opened a facility near Karolinska's campus in north Stockholm last summer and has been receiving orders from customers, mainly academic researchers, ever since. The company started out small and was able to commence operations without investors through sales of its services.

"We are just growing organically through the activities we do," said Ziegenhain. "It's a different approach."

It was demand for the founders' expertise and technology that caused them to set up Xpress Genomics in the first place. The Sandberg Lab was responsible in part for the creation of Smart-seq, a method first published in 2012 that enabled the sequencing of RNA from single cells, providing richer information on alternative transcript isoforms, SNPs, and supporting single-cell transcriptomics. The lab improved upon the original Smart-seq, describing Smart-seq2 in a 2013 publication, and Smart-seq3 in a Nature Biotechnology paper in 2020.

A newer, 384-well plate-based method called Smart-seq3xpress was described by Ziegenhain, Sandberg, and Hagemann-Jensen in Nature Biotechnology in 2022. The method miniaturizes and streamlines the group's Smart-seq3 protocol, reducing reagent use and increasing cellular throughput, and enabling full-transcript coverage, according to the paper.

These publications were all the marketing the group needed to get started. "We have been developing methods for years on the academic side, but we decided we couldn't support everyone who contacted us by teaching them the methods or collaborating," said Ziegenhain.

Xpress Genomics was thus born to implement more efficient and miniaturized RNA sequencing in robotic workflows. The company has yet to publish details on these newer iterations but expects papers to be published soon that include data generated by its customers.

The company currently has three full-time employees, and most customers are academics at the Karolinska Institute or elsewhere. The company does not publish its prices, but Ziegenhain said that its customers typically pay three or four times more to have the same data generated at government-subsidized core facilities.

"Our approach is much more cost-effective since we do large batches of data production," he said, further noting that pricing is dependent on scale.

MGI partnership

In 2023 the company announced its collaboration with MGI (also known as MGI Tech), an independent affiliate of BGI Group that provides a suite of sequencing instruments branded as DNBSeq.

According to Ziegenhain, he has been a user of MGI sequencers for four years and was among the first users in Scandinavia. Specifically, Ziegenhain and Xpress have used the DNBSeq-G99, G400, and T7 platforms. He described these "as providing high-quality data" and being "quite cost-effective," which is passed on to Xpress Genomics' customers.

As part of their agreement, MGI licensed know-how from Xpress Genomics related to single-cell RNA-seq library prep and automation techniques for full-length transcript analysis. Now, Ziegenhain said, MGI is "working to make a product they can sell based on the technology we use in our service."

"We felt like we were never going to go into making kits or providing laboratory equipment," Ziegenhain added. "That is much better suited to a company like MGI that has a full portfolio, including automation equipment, kits, sequencing, and informatics. It was something we could not implement ourselves in a reasonable time frame."

An MGI spokesperson this week confirmed that the company continues the previously announced development work and said more details around the project would be available at the end of the year. The spokesperson said that the company was drawn to the fact that Xpress Genomics' technology for scalable single-cell RNA sequencing "does not sacrifice quality or coverage."

The spokesperson added that these products would be sold worldwide.

MGI also does business in the US through Complete Genomics, and both have been under pressure recently because of a proposed bill in the US called the Biosecure Act, which aims to ban federally funded medical providers from using products or services from what it deems to be "foreign adversary biotech companies of concern" on account of data security.

Ziegenhain said that Xpress is aware of the proposed bill in the US and stressed that it takes data privacy and security seriously. "With regards to MGI's sequencing equipment, it is quite clear that there is no risk of any unauthorized data sharing, and all of our customers' data is only stored and processed using in-house servers at Xpress Genomics premises," Ziegenhain said.

Meanwhile, Xpress Genomics continues to improve its services. Ziegenhain said that offering spatial transcriptomics on its platform is something that will "surely meet a need" in the market, calling it "very complementary" to the company's single-cell genomics data.

"Many researchers want the combination of spatial and deep single-cell profiling," he said. The company is also interested in hiring to support its R&D and services.

In terms of competition, Ziegenhain said that Xpress Genomics' offering will "not replace everything in the single-cell space," but said the data it generates is an order of magnitude greater than what was previously attainable, offering access to alternative splicing data or genetic variation transcripts, making it "super relevant" for cancer studies.

"It opens up so many questions that have not been answerable with what we did with Smart-seq before," he said.