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Germany's Actome Embarks on New Project to Enable NGS-Based Protein Biomarker Detection


NEW YORK – The European Innovation Council recently awarded Actome €2.5 million ($2.7 million) to support the deployment of its protein interaction coupling (PICO) technology on next-generation sequencing instruments.

As part of the EIC-funded project, which commenced this month, the German biotechnology firm will invest about €1 million of its own, bringing the total budget for the effort, called PICO-NGS, to €3.5 million.

Founded in 2017 in Freiburg, a university city in southwest Germany, Actome has already commercialized its PICO platform, which relies on labeling antibodies with tailored DNA oligonucleotides, called PICO labels, and then analyzing the binding of at least two antibodies to proteins using digital PCR and its Amulator software.

The company maintains that the digital PCR format enables high sensitivity, absolute quantification, and multiplexing of up to four antibodies per assay. Last year, it announced an agreement with Qiagen to offer its protein analysis assays on that firm's QIAcuity digital PCR platform. Qiagen also made an investment of undisclosed size in Actome.

According to Peter Koltay, Actome's cofounder, the relationship with Qiagen is currently exclusive as far as digital PCR goes. But the firm would also like to enable the use of its PICO technology on DNA sequencing instruments, which is why it applied for and received the new EIC grant, which runs for two years.

The company's rationale for expanding PICO to sequencing is to boost its multiplexing capabilities, Koltay said. "In digital PCR, you have four or five fluorescent channels that you can sufficiently separate, which means you can measure four to five antibodies simultaneously on your sample and see what is going on, which proteins you have, and which ones are interacting," he said.

By moving to sequencing, Actome will be able to do the same, only at a greater scale. "We expect that we could be able to measure about 50 to 100 antibodies at the same time in a single cell," he said. "So you could project 100 antibodies into a single cell and see what they are doing, which is just not possible with digital PCR simultaneously."

According to Koltay, it's unclear which sequencing platform Actome will select for the new project. While the company would like to see its technology applied on different kinds of sequencers, given the challenges associated with such implementation, Actome will likely start with one platform.

Koltay, a German with Hungarian roots, joined Actome — initially founded by Csaba Jeney, a Hungarian scientist and senior lecturer at Semmelweis University Budapest, and his partner Attila Karsai — six years ago. At its earliest stages, Actome worked to demonstrate proof of principle for its PICO technology, and in 2019, Jeney and colleagues described the technology in a Nature paper related to bat influenza viruses. A second paper, on which Koltay was an author, was published in PLOS One in 2021, describing the use of the company's technology to characterize CRISPR-Cas9-engineered cells.

The company began to commercialize its technology around the same time, announcing a seed financing round of undisclosed size led by Qiagen and B.value, a Düsseldorf-based seed venture capital provider. Early customers have included both pharmaceutical companies and academic researchers. Koltay noted that Freiburg is just an hour's drive from Basel, Switzerland, where Roche, Abbott, Bayer, Lonza, and Novartis have operations, among others.

All of the firm's first adopters have been using digital PCR as their readout technology, Koltay noted. In Actome's PICO assay, antibodies are incubated with targets, forming complexes that the firm internally refers to as "couplexes." These consist of a target and two antibodies with attached DNA labels and are isolated into separate compartments, where they are amplified in a digital PCR reaction. Allowing every PCR reaction to start from a single molecule reduces background noise and competing reactions and improves data quality, Koltay said.

Actome has been selling its assays for use on the QIAcuity platform but also recently began offering the PICO technology as a service. "Many customers prefer to start with services," Koltay said, adding that it is likely Actome will also introduce PICO-NGS as a service.

"We could offer customers the ability to look at single cells for specific protein targets," he suggested. "They could provide the samples, and we would run the assays and provide the data back," he said. "That would be the first entry into the commercial field of this technology."

The company, which has 15 staffers and continues to hire, is also seeking additional funding, though Koltay declined to say how much.

Among Actome's potential competitors is Uppsala, Sweden-based Olink and its multiplex proximity extension assay technology. The company just launched its Explore HT platform, which can measure more than 5,300 proteins in as little as 2 µl of sample and offers a menu of products that use digital PCR or sequencing for readout. There is also SomaLogic, a Boulder, Colorado-based company that relies on aptamers to measure proteins in its multiplex SomaScan assays.

"These companies can screen a lot of targets simultaneously," Koltay said of both firms. However, Actome can separate molecules prior to amplification, as opposed to Olink's method, which amplifies molecules in bulk using rolling circle amplification, he noted. "Though we cannot offer such large panels of antibodies yet, we are convinced that we can provide higher quality data because we have less cross-talk in the amplification reaction," he said.

All companies are poised to benefit from increased interest in proteomics, Koltay said. "[A]s soon as people will be able to know anything they want to know about the nucleic acids, they will start looking more into proteins. Actually, this is happening already."

"Ultimately, you want to be able to look at proteins at the single-cell level," he added. "This would give the best understanding of what the cells are doing in a certain disease situation."