CLN - Feature
Linus Bosaeus, CEO of Rarity Bioscience, had just exited the stage at ADLM 2025 after presenting about his company’s superRCA assay and was catching up with colleagues when he got the good news: The audience vote had come in, naming his product as the fan favorite of this year’s ADLM Disruptive Technology Award competition. The official judges' vote came in shortly after, echoing the audiences' choice and confirming Rarity Bioscience as the winner of the award.
“I was surprised because it was so quick,” Bosaeus said, “but I guess that was good. I didn’t have to stand there and be nervous.”
SuperRCA is an ultrasensitive multiplex assay that detects very small amounts of DNA sequence variants, such as mutations, in tissue and blood samples. In fact, it can detect one single nucleotide out of 100,000 wild-type DNA molecules. As explained by Bosaeus, it converts DNA into fluorescent particles and enables detection of mutations using conventional flow cytometry, and it can be performed in most laboratories using existing equipment. Currently, the technology is targeting detection of minimal residual disease (MRD) in cancers during or after treatment.
“In the follow-up setting, you no longer have a tumor to biopsy, so you’re relying on a liquid biopsy — a blood sample,” Bosaeus said. “For that, you need a very sensitive test, because your mutation levels are supposedly zero. You’re measuring from the ground up. You also need something inexpensive that you can do frequently.
“In an acute leukemia, your relapse can happen in weeks or months, so it’s really quick,” he added. “You need to have a test that is available close to patients and that gives you a result, ideally, the same day. If a patient receives a bone marrow transplant or undergoes some specialized treatment, getting that measurement is critical.”
SuperRCA is such a test. It returns results in 5 hours and 40 minutes, he said, and 96 samples can be run in one go.
The superRCA technology combines rolling circle amplification (RCA) and padlock probes in a novel way for highly specific nucleic acid sequences detection. This method generates a relatively large, self-contained structure that can be analyzed using microscopy or automated flow cytometry. RCA is an isothermal amplification method that uses a circular DNA template to produce large amounts of DNA from a small initial sample. Padlock probes are short DNA oligonucleotides with segments at the 3’ and 5’ ends that are complementary to a target region.
Here’s a more detailed explanation of how superRCA works from Rarity Bioscience’s website (raritybioscience.com): DNA is extracted from a sample of whole blood, bone marrow, or tissue. Then, DNA sequences of interest that are known to be mutated in malignant cells are enriched by a limited pre-PCR (~10 cycle) amplification. The enriched sample then undergoes a ligase-mediated circularization of one strand. Next, the circularized strands containing the target region are amplified by the first RCA step. This is followed by a genotyping padlock probe ligation and a highly specific, second RCA step in which the second RCA encircles the first RCA product to form large superRCA structures that can be analyzed by flow cytometry. Finally, the superRCA products can be enumerated as mutant- or wildtype-specific using fluorophore-labeled hybridization probes and recorded as individual, fluorescent objects in a standard flow cytometer. For multiplex assays, analysis is done similarly using multiple fluorophores and wavelengths.
“What we are doing differently is that we are applying padlocks on an already preamplified target,” Bosaeus said. “We use an RCA in the first step, and then apply the padlock and do a second RCA. So we call the technology superRCA because we do it twice. This allows us to make extremely large particles and get a very high fluorescent intensity.
“The initial idea was just to increase fluorescent intensity, to reduce signal to noise for any type of assay,” he added. “Serendipitously, it was discovered that by doing it this way, we actually get a very good allele distinction, basically getting increased specificity over, for example, PCR-based technologies.”
Because the assay can be run on standard flow cytometry equipment, the company has earned a lot of attention from more resource-limited countries in southern Europe, South America, and elsewhere that may not have digital PCR or other advanced technologies, Bosaeus said. “That’s an interesting observation that we didn’t really expect or foresee.”
The product builds on technology developed at Sweden’s Uppsala University by Ulf Landegren, MD, PhD, a professor of immunology, genetics, and pathology. Landegren had commercialized RCA and padlocks for other applications and spun out several different companies, including Olink Proteomics, Bosaeus said. When Lei Chen, PhD, Rarity’s co-founder and chief technology officer, was a doctorate student working under Landegren, the techniques were largely applied to proteins. But Chen had the idea to try to apply the technology to nucleic acids using the double RCA approach.
“[As] with all the great inventions, this was not supposed to work,” Bosaeus said. Landegren told Chen it had been tested before and couldn’t be done. “But Dr. Chen didn’t take no for an answer and got data to prove that it can actually work.” Chen has worked on these techniques for the past 10 years.
Rarity Biosciences was established 4 years ago and began offering the assays for research collaborations about 2.5 years ago, Bosaeus said. While they considered different readout platforms, they ultimately went with flow cytometry because it is the most readily available instrument in hematology and pathology, he said. The company now has ongoing research collaborations for about 10 cancer types, including leukemia, lymphoma, glioblastoma, melanoma, and lung and colorectal cancers. “We [also] just launched our first off-the-shelf kits at the end of last year, enabling decentralized use,” he said.
The company has been part of several impactful peer-reviewed studies that Bosaeus presented at the meeting. One showed how superRCA could help monitor leukemia patients through detection of sequence variants and early disease recurrence (Nat Commun 2022; doi: 10.1038/s41467-022-31397-y). One demonstrated that superRCA could be used to monitor colorectal cancer patients by analyzing hotspot mutations in cell-free DNA and identifying changes in mutant allele frequency in patients with clinical relapse (Cancers 2024; doi.org/10.3390/cancers16030549). A third used superRCA to measure IDH1/2 mutations as biomarkers for detection of MRD in patients with acute myeloid leukemias (Blood Adv 2025; doi.org/10.1182/bloodadvances.2025016726).
Another study of over 330 patients that’s still in press used superRCA to improve diagnostic screening and classification of clonal mast cell disease.
“Even though we are sort of early-stage, we have run thousands of retrospective biobank samples,” Bosaeus said. “Anything that is mutation-driven, we can analyze.”
Overall, published papers demonstrate superRCA’s sensitivity to be 10−100 times that of digital PCR, Bosaeus said. The tool can be helpful in monitoring cancer patients, he said, such as when you need to determine if a patient experiencing residual mutations after a third round of chemotherapy should go on for a fourth, or receive a complementary treatment. Following bone marrow transplant — a treatment for many leukemias — the test could detect early so-called relapsing mutations (i.e., those that return) so that clinicians can gain time to adjust treatment accordingly. The technology also can be helpful in early detection of drug resistance, he said, allowing clinicians to switch treatments. “You enable precision medicine by having more frequent, accurate diagnostics,” he said.
The other award finalists were Chemeleon, for its BINDS-AMI assay, and MagIC Lifescience, for its MagChipR platform.
The proprietary binding-induced nanostructure dynamic surface (BINDS) assay is an instrument-free diagnostic platform that enables rapid, high-sensitivity biomarker detection, delivering results in under 2 minutes. Chemeleon’s lead product targets acute myocardial infarction (AMI) by detecting and quantifying cardiac troponins with 99.2% sensitivity and 90.5% specificity.
The MagChipR platform is an ultra-fast PCR system with high multiplexing capability that delivers lab-quality pathogen and antimicrobial susceptibility results in under 20 minutes. The technology enables same-visit diagnosis and treatment. MagChipR’s first commercial application targets the rising epidemic of sexually transmitted infections, offering a single-test panel for Chlamydia trachomatis, Neisseria gonorrhoeae (NG), Trichomonas vaginalis, and Mycoplasma genitalium (MG). If NG or MG are detected, the platform performs antimicrobial susceptibility testing using high-resolution melt analysis.
Karen Blum is a freelance medical and science writer in Owings Mills, Maryland. +Email: [email protected]