Therapeutic RNAs including microRNAs (miRNA, small, non-coding, regulatory but unstable nucleosides) and messenger RNAs (mRNAs) are part of the therapeutic arsenal for tissue regeneration. CARN proposes the development of bio-drugs using EVs and synthetic lipid vesicles as RNAs delivery systems for skeleton regeneration. EVs isolated from mesenchymal stromal cells (MSC) reproduce the therapeutic effect of their parental cells and are of real therapeutic interest in regenerative medicine. They contain proteins, lipids and also nucleic acids, in particular miRNAs which are responsible for their biological effect. EVs are also being developed as targeted delivery systems due to their abilities to deliver therapeutic cargo specifically into tissues and their exceptional endosomal escape and intracytosolic delivery of RNA. 

In the CARN project, microRNAs targeting various pathological processes (inflammation, apoptosis, senescence) and mRNAs encoding factors (transcription factors, growth factors, anti-geronic factors) involved in bone and joint regeneration and in the immunosuppressive effects of MSCs will be formulated and encapsulated in these innovative hybrid functionalized vesicles. By proposing functionalized hybrid EVs decorated with recognition elements and containing disease-modifying therapeutic RNAs, CARN will allow hybrid EVs to open new therapeutic windows in the treatment of skeletal diseases.

Extracellular vesicles (EVs) are nanometric lipid bilayer vesicles released by cells. They play a central role in cell-to-cell communication via ligand signalling and shuttling of cargo between cells; they transfer information in the form of proteins, lipids and acid nucleic between the cells. Among those vesicles, exosomes are considered as highly promising biomarkers, notably for cancer, as they reflect the biologic signature of their parent cells in the form of a diverse biological content. Moreover, they can be directly collected by liquid biopsy, without the need for heavy and dangerous operations, at high concentrations. As systems are developed to acquire a better understanding of the role in the organism, researchers have to face numerous challenges: nanometric particles are difficult to handle and visualize, their concentration in blood is close to picomoles and they present a high heterogeneity in size and content. As scientists acquire a better understanding of EVs, it appears that this heterogeneity carries essential information that could help us identify markers of interest. One of the main challenges when working with EVs as biomarkers is the diversity results obtained. 

The objective of the IMPED project is to build a platform to study extracellular vesicles (EVs) in their globality, coupling protein and nucleic acid detection. The platform would allow to process and analyse patient samples on a same device, assembling extraction and purification of EVs from the sample, analysis of the biomarkers either on the external membrane or encapsulated inside the vesicle.

In the realm of cancer research, exosomes—tiny droplets secreted by cells—hold vital information, acting as messengers between cells and playing a crucial role in diseases like cancer. However, current technologies lack the sensitivity to analyze individual exosomes, requiring bulk processing that leads to the loss of crucial information. McGill University's David Juncker introduced Digital Omics of Single Exosomes (DOSE), a groundbreaking technology funded by Genome Canada's Innovation Breakthrough in Genomics competition. DOSE allows the simultaneous analysis of millions of exosomes, offering the potential to decode their content and distinguish between healthy and diseased cells. The technology's development holds promise for advancing cancer diagnostics, clinical trials, and overall cancer management, with a potential impact on the $40 billion cancer diagnostics market.

CATCH-U-DNA project aims to replace the labor-intensive, occasionally biased and costly PCR method with a simple non-PCR DNA quantification method by exploiting, for the first time, hydrodynamic properties of DNA chains. It is a novel sensing concept that uses acoustic wave sensors.

CATCH-U-DNA will apply an integrated acoustic platform in the detection of common mutations occurring in colorectal and lung cancers, i.e. KRAS, EGFR and BRAF in serum. The results will be compared to the findings using NGS and real-time PCR based on tumor tissue and serum samples obtained from patients.

The aim of Project INDEX is to isolate and characterize nanoparticles available in bodily fluids through development and integration of novel technological breakthroughs. The technology will enable the analysis of clinically valuable nanoparticles called exosomes towards new generation diagnostics. Exosomes are known to mediate communication between cells and their effective utilization holds a great promise of revolutionizing the standard of clinical care. However, their detection and molecular profiling is technically challenging. The proposed technology will isolate exosomes that are as small as 30nm in diameter from human plasma with high purity, and provide in-depth, multi-parameter characterization of the particles through digital counting, size determination, and biological phenotyping.

Preeclampsia is a hypertensive disorder of pregnancy associated with significant maternal and perinatal mortality and morbidity. Currently, there is no curative treatment for preeclampsia, and delivery and placental delivery are the only means of recovery. Developing therapeutic strategies for preeclampsia is a major priority in perinatal medicine. During preeclampsia, large quantities of sFlt-1, a soluble form of vascular endothelial growth factor receptor 1, are released by the placenta, inhibiting the pro-angiogenic effects of VEGF and PlGF on maternal endothelium. These angiogenic factors are crucial for endothelial survival, explaining endothelial dysfunction in preeclampsia. Studies suggest that extracorporeal apheresis can reduce circulating sFlt-1 and prolong pregnancy, but potential adverse effects are associated with non-specific systems. The APHERESE project proposes a specific and competitive apheresis approach, validated with a dynamic microfluidic filter. Experiments with VEGF-coated magnetic beads demonstrated effective capture of sFlt-1 and release of PlGF, thus opening new perspectives for preeclampsia treatment.