Diagnostics
ONCOLOGY
The unique capacity of NBI to isolate intact and polydisperse vesicles enables the development of new approaches to detect early cancer or Minimal Residual Disease (MRD) biomarkers based on combinations of several markers.
Electron Microscopy image of particles isolated by NBI showing intact and polydisperse vesicles.
For example, the combination of 2 luminal markers of vesicles has the potential to distinguish vesicles produced in early gastrointestinal cancer patients from the background of vesicles produced by blood cells in healthy donors.
In addition, thanks to its easy setup, quick readout time, low cost-of-goods, and high reproducibility, NBI can also revolutionize other biomarker assays initially developed on exosomes isolated with ultracentrifugation or other technologies. EVbiome is currently transferring its know-how to a Swiss start-up to improve its screening asset.
NEURODEGENERATIVE DISEASES
A sub-family of neurodegenerative diseases include conditions where damages to neurons are directly or indirectly caused by the massive production of aberrant and/or misfolded proteins. As a mechanism of protection, body cells are attempting to get rid of these malignant proteins by excreting them through exosomes. This is well documented in Cerebrospinal Fluid (CSF) but screening in CSF requires lumbar punctures and is therefore not translatable in clinical practice. Here again EVbiome technology has the potential to detect in blood early biomarkers of neurodegenerative diseases such as Parkinson Disease, Alzheimer Disease, or prion diseases.
In a pilot project, α-Synuclein was detected in EVs derived from human plasma and CSF. Detected levels in plasma are 10x higher in EVs isolated with NBI as compared with ultracentrifugation (UC), thus offering opportunities to develop early diagnostics tools in Parkinson Disease.
EVbiome is currently collaborating with the University of Bologna (Italy) to adapt the RT-QuIC assay [Ref] on the detection of Parkinson Disease and Creutzfeldt-Jakob misfolded proteins on vesicles isolated with NBI.
INFECTIOUS DISEASES
NBI has the potential to support the diagnostics of infectious diseases caused by bacteria or viruses. In such diseases, the presence of the pathogen is usually detected either by circulating traces of nucleic acids, either by the consequences of the infection (e.g., antigens or symptoms), which does not permit distinguishing active ongoing infections from past infections or dead pathogens.
Bacteria are known to produce EV-like vesicles named Outer Membrane Vesicles (OMVs) [Ref]. For example, Borrelia burgdoferi, the bacteria responsible for the Lyme disease, produces OMVs that contain bacterial transcript. Molecular diagnosis of Lyme disease is known to be problematic. Digital droplet PCR (ddPCR) on plasma to detect Borrelia burgdoferi has been reported with 58.5% sensitivity vs 24.4% specificity with two-tiered serology at clinical diagnosis [Ref]. The detection of bacterial transcripts in OMVs after proper isolation might improve the assay by improving the sensitivity and focusing on the detection of biologically active pathogens.
Our platform has also the potential to detect “live viruses” within vesicles. For example, we have shotgun-sequenced RNA from isolated vesicles of 8 oncology patients and incidentally detected that, in one only out of the 8 subjects, a high proportion of non-human reads mapped to the GB virus C (hepatitis G virus, or Pegivirus C), an asymptomatic virus known to infect about 2% of the general population.
Fig. Legend: Mapping of 278 reads (out of 10’000 sampled non-human or unmapped reads) to the viral genome of GB virus C.