Since 2001’s discovery of microRNAs (miRNAs) in humans, progress in genomics and transcriptomics has increased our comprehension of gene expression regulation. miRNAs are small, noncoding RNA molecules showing huge promise as clinical biomarkers and diagnostic tools for illness and disease, as significant changes in their expression occur in response to pathological states. However, miRNA detection is still challenging nowadays, since costly, complex sample preparations and RNA amplifications are not yet reliable enough for clinical decision making. In this context, three innovative EU companies, Optoi Microelectronics - with microelectronic knowhow and manufacturing skills - DestiNA Genomics - with ‘error free’ chemical technology for microRNAs recognition – and GeneXplain – with bioinformatic capabilities - joined forces with four key academic research groups from the Universities of Trento (Italy), Granada (Spain), Hannover Medical School (Germany) and Santa Catarina (Brazil). All the parties combined their knowledge with respect to miRNA biomarkers with a particular focus on lung cancer, to develop a novel and reliable miRNA detection system for this disease. To this end, research collaborations will address the analysis of miRNAs specifically over-expressed in lung cancer, continuing experimental work already started in the past years, but with greater integration and focus. Existing close partnerships with healthcare institutions will be strengthened, ensuring multi-site and multi-ethnic sampling. In parallel, optimization and validation of a miRNA detection kit based on Optoi semiconductor optical detector will continue. The DestiNA patented technology for specific nucleic acid recognition will be refined to reach the integration and result reliability required for use in clinical point of care testing. The strong network created between the companies and the academic institutions will thus provide a unique scientific and technological environment to turn the research outputs into an innovative product for healthcare advance and progress.

This visionary project addresses the key needs of patients, clinicians and the World Health Organisations stated deliverables of affordable, reliable and point-of-care molecular TB diagnostics, with the vision of removing the need for centralised facilities and offering remote primary care diagnosis coupled with telemetry for “cloud based” notification to ensure public health and surveillance interventions. The core technology deliverables will include: Rapid screening of TB infection (within 30 mins): We will develop low-cost portable optical devices and chemical molecular probes for accurate and rapid ‘triage tests’ to allow ‘no-wash’ detection of Mycobacteria ‘in-field’ in sputum at costs comparable with or lower than existing microscopy-based methods. This technology has the aim of replacing current sputum-based microscopy methods. Rapid molecular identification of drug resistance (within 2 hours): We will develop novel low-cost assays based on molecular methods that will allow accurate and rapid screening for the Mycobacterium tuberculosis complex in sputum and drug-resistant tuberculosis, thus providing rapid screening of at risk groups for TB as well as identification of drug resistance profiles. Biomarkers for early diagnosis and assessing treatment response: A higher risk element is the development of point-of-care diagnostics for quantification of microRNAs (that are known to be modulated during progression from latent to active TB and during treatment progression), directly from small blood samples. We will ensure that the technologies are economically viable in the context of resource poor settings – indeed the whole project will be driven by practical need and local resourcing constraints – NOT imposition. Thus it will require negligible initial costs for implementation, minimal training and expertise, with the running costs less than 1/10 th of current detection technologies, thereby addressing a key objective of the work program.

Circulating cell-free ribonucleic acids (ccfRNAs) represent an emerging and important class of molecules, able to provide significant clinical relevance as novel screening, prognostic and therapy monitoring biomarkers in cancer. Through analysing specific ccfRNAs, different cancers can be accurately correlated for type and stage. Sadly, despite extensive academic and clinical research identifying and validating in limited clinical trials, ccfRNAs have not yet entered the field of clinical diagnostics. This is amongst others because the current analytical methods remain less than satisfactory, and until now ccfRNA detection remains therefore challenging, costly, and requires elaborate multi-step sample preparations. Prompted by these current analytical limitations, two innovative EU companies, DESTINA Genomica SL (Spain) and OPTOELETTRONICA ITALIA SRL (Italy) have developed the “ODG Platform” for direct quantitative measurement of circulating RNA molecules. The diaRNAgnosis project objective is to complete development of the ODG platform, delivering reliable and robust detection of novel ccfRNA signatures that could be linked to specific cancer types. To ensure timely delivery and success of the diaRNAgnosis project, DESTINA and OPTOI have considered and invited partners who they believe will add real value to the consortium. These are the Spanish company NanoGetic SL (specializing in nanotechnologies); three key academic research groups from the Universities of Trento and Catania (Italy), Granada (Spain); as well as the Princess Máxima Center (The Netherlands). This new pan-European, multidisciplinary and intersectoral team will develop a reliable and innovative method and platform to identify cancer biomarkers in liquid biopsies. The research collaboration will address the need to perform high sensitivity/high specificity analysis of ccfRNAs that are specifically and overexpressed in testicular germ cell tumour (TGCT) and prostate cancer (PCa) respectively.