NEW YORK – With its recently announced acquisition of San Diego-based DNA nanotechnology firm Palamedrix for up to $52.5 million, SomaLogic aims to develop more compact and accessible versions of its SomaScan proteomic platform.
Longer term, SomaLogic envisions Palamedrix's DNA-based biosensing technology, which consists of DNA origami structures functionalized with affinity reagents, as potentially enabling new assay formats and functionalities for its Somamer affinity reagents, which are likewise nucleic acid-based, said Jason Cleveland, the company's chief technology officer.
Cleveland said he expects SomaLogic to release products incorporating Palamedrix's technology within the next several years, such as smaller, targeted biomarker panels for use in areas like biopharma research and diagnostics.
Launched two years ago by Shane Bowen, formerly senior director of scientific research at Illumina; Paul Rothemund, research professor in bioengineering at the California Institute of Technology; and Ashwin Gopinath, assistant professor at the Massachusetts Institute of Technology, Palamedrix has largely kept a low profile. Upon its launch, the company raised around $6 million in seed funding and has since secured bridge funding of an undisclosed amount. It currently has around 15 employees, said Gopinath, who SomaLogic plans to retain, along with the firm’s existing offices and lab space.
Palamedrix was founded to commercialize DNA origami technology invented in Rothemund's lab, where Gopinath was previously a postdoc. DNA origami involves folding long nucleic acid strands to create three-dimensional nanoscale structures. Palamedrix is using the technology to produce single-molecule biosensors that are functionalized with affinity reagents, such as antibodies, and has devised an approach that lets it place millions of individual DNA origami-based sensors on semiconductor chips, allowing the creation of massive arrays of individual single-molecule sensors.
The company can functionalize each DNA origami sensor with pairs of antibodies to a particular protein target, producing millions of what are essentially sandwich ELISAs. When both antibodies in a pair bind to their target, it triggers the production of a DNA molecule that can be detected via methods like digital PCR. According to Gopinath, Palamedrix believes the approach will enable rapid, inexpensive, and highly multiplexed proteomic experiments.
He said that in internal work, the company has demonstrated that it can detect proteins at the single-molecule level using commercially available semiconductor chips and antibody pairs.
Gopinath said that Palamedrix's approach has a number of advantages compared to existing affinity-based proteomic platforms from companies like Olink, NanoMosaic, and SomaLogic. For example, it can measure proteins at the single-molecule level, and it eliminates affinity reagent cross-talk by confining each individual reaction to a discrete DNA origami sensor.
He suggested that this latter feature would help the company rapidly scale its assay library. While Palamedrix's multiplexing capabilities, like those of other affinity-based proteomic platforms, are constrained by the availability of quality reagents for detecting protein targets, the elimination of cross-talk means it could potentially have looser criteria for its antibody pairs.
"It makes antibody selection, or affinity binder selection, a whole lot easier," he said.
SomaLogic, of course, does not use antibodies for its protein assays, relying instead on its proprietary aptamers, or Somamers. Palamedrix's sensors can be functionalized with Somamers or other affinity reagents in much the same way as they can with antibodies, but Cleveland said the fact that both the Palamedrix sensors and Somamers are nucleic acid-based raises the possibility of more unique integrations down the road.
"You can think about [affinity] reagents where you design them with the origami in mind," he said. "For example, people have made [origamis] that look like flytraps that can spring open or spring closed based on the binding of a molecule. You might have a piece of DNA that is complementary to the origami and acts as a latch and another piece that acts as an affinity reagent to the protein."
"That sort of thing is further in the future, but that is one of the things that is exciting — it's just a super natural fit between Somamers as affinity reagents and DNA as the building blocks of these little [origami] machines," he said.
Nearer term, Cleveland said, SomaLogic envisions Palamedrix's technology as enabling smaller chip-based systems that could be used for running its assays. He noted that the existing SomaScan assay, which measures roughly 7,000 protein targets, requires large liquid handling systems that take up substantial amounts of bench space.
"I view the Palamedrix technology as enabling us to get into much smaller footprint boxes," he said. "If you can get proteomics down to a sort of benchtop-size device at an attractive price point, then there are a lot more places where you can go in the world. You can imagine, ultimately, devices sitting in hospitals, in [reference labs], places like that. I think that is the ultimate path for SomaScan."
In addition to a more compact and potentially less expensive assay, the Palamedrix platform would provide a sensitivity boost, enabling single-molecule measurements. According to Cleveland, the existing SomaScan system has sensitivity down to a few hundred molecules.
While SomaLogic's end goal is to put the full SomaScan assay in a next-generation format incorporating Palamedrix's technology, initial efforts will likely revolve around more targeted assay panels, he said.
He cited the company's SomaSignal diagnostic assays as an area where the Palamedrix technology could prove useful. SomaLogic currently offers around 20 SomaSignal assays, such as for predicting risk of cardiovascular events and identifying individuals with excess liver fat. The firm has said it aims to expand its offerings to around 30 tests by the end of the year and that it believes it currently has enough data to support development of 80 to 100 assays.
While the SomaSignal tests use just a subset of the total SomaScan panel, SomaLogic runs the full panel when making measurements for the tests. Cleveland said the company could use Palamedrix's platform for more targeted panels consisting of only the proteins composing the SomaSignal tests, a format that he suggested would be better suited to broader distribution, allowing clinicians to make measurements at their facilities as opposed to having to send samples to SomaLogic.
In terms of developing the technology for proteome-scale measurements, Palamedrix's Gopinath said the company has not yet tried to "push the limits" of its platform and has thus far maxed out its arrays at several hundred million sensors. Recent work from fellow proteomics firm Nautilus suggests, though, that a DNA origami-based approach could enable proteome-scale analyses.
Seattle-based Nautilus' approach to proteomics is fundamentally different from either SomaLogic's or Palamedrix's, but the company is using arrays of DNA origami structures to capture and secure individual proteins for analysis.
In a recent interview with GenomeWeb, Parag Mallick, Nautilus' cofounder and chief scientist, said the firm has demonstrated the ability to affix up to 10 billion individual proteins to its chips using biological samples including cell lysates. In theory, an array that size would allow it to analyze proteomes across a dynamic range as large as 109 to 1011.