KariusThe startup Karius aims to help establish a world where infectious disease is no longer a major threat to human health.

“It’s an audacious vision,” said Dr. Brad Perkins, chief medical officer at Karius. “But I think it’s commensurate with the platform we’ve developed and continue to evolve.”

The Redwood City, California-based company has developed Karius Test, a liquid biopsy for infectious diseases that can detect more than one thousand pathogens from a single blood draw.

Bradley Perkins, MD, Chief Medical Officer, Karius

Dr. Bradley Perkins [Image courtesy of Karius]

The test works by detecting microbial cell-free DNA (mcfDNA) in the bloodstream from likely pathogens causing an infection.

“If we can accelerate and improve diagnosis while making it safer, the notion is that clinicians will ultimately be better able to treat infectious diseases,” Perkins said.

Karius says its technology could play a role in helping clinicians provide more targeted antimicrobial therapy. “Broad-spectrum antibiotic treatment is often used due to a lack of a precise diagnosis,” Perkins said.

“Improving infectious disease diagnostics can guide physicians to use antimicrobial agents more selectively, potentially enabling a world where infectious diseases are no longer a threat to humans,” Perkins said.

“Extending out from that, there are lots of opportunities to look at public health applications in pandemic preparedness,” Perkins said. “And that’s down the road for Karius. We are committed to that vision. And we think this is a realistic technology to move us toward that world.”

While scientists recognized cell-free DNA as an analyte in the 1940s in the context of oncology, it wasn’t until recently that researchers could tap its potential for various clinical uses, including non-invasive pregnancy testing and reducing the risk of organ transplant rejection.

Karius traces its origins back to research carried out in the lab of Stanford University professor Stephen Quake.

In 2014, the company’s two co-founders, Dr. Mickey Kertesz and Dr. Tim Blauwkamp were investigating the use of cell-free DNA to reduce the risk of organ rejection when they found a microbial signature in the patients’ blood samples.

“The challenge was that there is a range of concentrations of cell-free DNA across various uses,” Perkins said.

Fetal DNA in expectant mothers is the highest concentration of cell-free DNA researchers have identified. “Almost 10% of cell-free DNA circulating in mom’s blood is fetal in origin,” Perkins said.

The quantity of microbial cell-free DNA in the blood is about five orders of magnitude (10% fetal, 0.001% mcfdna) less than fetal cell-free DNA. “So the first challenge that we had to overcome to commercialize this test was to find ways to enhance that microbial signal and suppress the background human DNA,” Perkins said.

The company also has focused on removing contaminants from the process, including microbial contaminants and contaminants introduced in the process of obtaining specimens and sending them to the lab.

Karius used AI to sift through more than one million publicly available databases of whole-genome sequences of microbial agents. “Only a very small fraction of those [databases] are of suitable quality to use as references to align our microbial cell-free DNA,” Perkins said.

Karius ended up with approximately 20,000 reference genomes for bacterial, viral, parasitic and fungal pathogens. The company then integrated those genomes with proprietary data to identify target pathogens and quantify the amount of pathogen-specific microbial cell-free DNA in plasma.

Perkins said that the broader life sciences industry needs new tools to fight infectious diseases because microbial pathogens are not genomically static. “They quickly acquire capabilities to resist our best efforts to treat them with various antimicrobial agents,” Perkins said.

The widespread use of antimicrobial agents for human health and agricultural applications exacerbates the problem. “And we now have a global public health crisis because we don’t do a good job diagnosing many infections, and the pipeline for creating new antimicrobial agents is dwindling rapidly,” Perkins added.

The World Health Organization says bacteria with AMR could kill 10 million people annually by 2050.