SAN FRANCISCO (GenomeWeb) – Molecular diagnostics startup Miroculus is going all in on microRNAs as the ideal blood-based biomarker for diagnosing and monitoring a number of diseases and even tracking an individual's general physiological well-being at the point of care and in resource-poor areas of the world, the company's chief technology officer said this week.
In a keynote presentation at Cambridge Healthtech Institute's Molecular Medicine Tri-Conference held here this week, CTO Jorge Soto unveiled the company's new open database of miRNA associations and interactions, and the latest iteration of an inexpensive desktop instrument for detecting and analyzing the biomarkers.
Based in San Francisco's Mission Bay area, Miroculus aims to tap into the growing evidence that miRNAs — small non-coding RNA molecules whose primary role is to regulate gene expression — can serve as powerful biomarkers for a number of conditions including various cancers and infectious diseases.
Soto noted in his presentation that miRNAs satisfy a large number of criteria for a useful biomarker, including the fact that they are highly stable and can be found in a variety of bodily fluids, including blood serum, plasma, saliva, and urine, meaning they can be detected relatively easily and noninvasively on a repeat basis over time.
Miroculus is clearly not alone in this idea: the company noted that between 2000 and mid-2015, there were more than 35,000 microRNA-related publications, and that number is growing at an almost exponential pace.
The company set out to create an open database of these publications and their findings, including miRNA associations with diseases and with other biomolecules, but "trawling through all this literature became impossible for a small company or even a larger company," Soto said. As such, Miroculus employed a Hadoop framework to process the data from all of these publications and create its Loom database, the first version of which is now live, displaying more than 600 miRNAS associated with nearly 1,200 conditions and regulating almost 3,400 genes.
This version, Soto noted, is currently being used by Miroculus' early partners, but it is open to everyone. And it is an ongoing process, as the company plans to update it later this month with many more features, miRNAs, and associations, Miroculus CEO Alejandro Tocigl told GenomeWeb in an interview following Soto's presentation.
But this is only one half of Miroculus' offering, as the firm has also developed Miriam, an instrument platform for detecting and analyzing miRNA biomarkers from patient samples. The company's workflow for this analysis is relatively straightforward: extract total RNA from a patient's biofluid sample; add specific probes and reagents for performing loop-mediated isothermal amplification; and amplify and detect the target molecules with a luminescent readout.
The first version of Miriam was essentially a well-plate reader with a port for smartphone-enabled scanning and detection. But at Tri-Con, Soto provided a glimpse of the new version of Miriam, which is an open-source isothermal amplification instrument based on the Arduino platform. The system can run LAMP or ELISA assays through a local computer, connecting via USB or WiFi.
Soto said that the platform's current limit of detection is about 1 attomolar, a figure the company believes it can still improve on. Early experiments have also shown that it is specific enough to distinguish between different miRNA isomiRs.
Miriam's open-source master program and platform design can be downloaded for free on GitHub, and the cost of materials for the current iteration of Miriam is only about $80. This is important, as Miroculus is especially interested in applying its technology in developing areas of the world.
So what can Miriam and Loom be used for? Soto conceded at Tri-Con that there are so many potential applications that the company has had some difficulty homing in on the killer apps, and so it is currently fostering collaborations with a number of partners in a variety of fields to help narrow this down.
For instance, Miroculus is working with researchers at the University of Edinburgh as part of a larger consortium funded by the Bill and Melinda Gates Foundation to combat river blindness, a parasite-caused disease that is the leading cause of blindness in the developing world.
In addition, Soto noted, the company is working with Johns Hopkins University, the University of California, San Francisco, and Universidad Peruana Cayetano Heredia in Lima, Peru, to create assays for early chagasic cardiomyopathy, a condition caused by infection with the Chagas-disease-causing parasite Trypanosoma cruzi and often resulting in heart failure. Soto presented early data showing that the collaborators were able to use a blood-based miRNA assay to distinguish Chagas from non-Chagas infection in 10 patients presenting with cardiomyopathy symptoms.
The company also has an ongoing collaboration with an unnamed partner in the area of early detection of gastric cancer, which disproportionately affects individuals in resource-poor areas of the world. This work, which involves developing a panel of miRNAs for early disease detection, is currently being expanded to include multiple partners and to examine larger cohorts, and the company hopes to share some early data in a few weeks, Soto said.
Finally, Soto showed some data demonstrating the use of Miroculus' platform to detect miRNAS as a surrogate marker of a person's general physiological condition. Specifically, company researchers tracked the level of various miRNAs in Soto's blood over five weeks. For two weeks he maintained his normal work, sleep, and exercise patterns, but in the third week he attended a CrossFit class with a friend and immediately saw a change in the levels of two specific miRNAs associated with muscle injury.
"Some would argue this application is insignificant in a world full of serious disease," Soto said. "But, it's proof of principle that these biomarkers can be so ubiquitous and inexpensively monitored to use in the developing world as accurate biomarker tests for a variety of health issues."
CEO Tocigl told GenomeWeb that Miroculus early last year set out to raise $3.6 million in angel and seed funding from private investors, and actually oversubscribed the round to $4.25 million. He said that the firm will soon look to raise additional funds but will wait until it releases some early study data, hopefully in the next month or two.