Excellence in research and development of non-coding RNA DIAGnostics in ONcology

Informations projet

RNADIAGON

N° de convention de subvention: 824036

DOI

10.3030/824036

Projet clôturé

Date de signature de la CE 18 Septembre 2018

Date de début 1 Février 2019

Date de fin 31 Juillet 2024

Financé au titre de

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Coût total

€ 662 400,00

Contribution de l’UE

€ 662 400,00

Coordonné par

Masarykova univerzita
Czechia

Periodic Reporting for period 2 - RNADIAGON (Excellence in research and development of non-coding RNA DIAGnostics in ONcology)

Période du rapport: 2022-08-01 au 2024-07-31

Résumé du contexte et des objectifs généraux du projet

Cancer occurs in more than 2 million individuals every year in Europe alone. It is widely recognized that early diagnosis and monitoring of the disease - during therapy and post-treatment follow-up- is a key step for successful patient management: it helps to offer on-time curative intervention and selecting the most appropriate therapy, improves the quality of life, while contributing to reduce the economic and social burden for both patients and society. Project RNADIAGON aimed at development of personal skills and knowledge of early-stage and experienced researchers working in the field of small non-coding RNA diagnostics from five European research institutions through their long-term stays at one of the world-leading ncRNAs research centers in United States and traineeships at the education center and manufacturing facilities of industrial partner developing small ncRNAs-based certified diagnostics. This research and innovation staff exchange was expected to increase the scientific excellence and quality of related research in the EU research institutions.

The expected impacts of RNADIAGON project on career prospects were fully accomplished. As planned, during the secondments of Early-Stage Researchers (ESR) and Experienced Researchers (ERs) at UNITEX, the secondees were trained at (i) advanced techniques and protocols on collection, processing and storage of clinical specimens and circulating extracellular vesicles as key and specific carriers of cellular components including small ncRNAs, (ii) cutting-edge technologies used in research of small ncRNAs as biomarkers in human cancers, and also (iii) basic research of biology and function of ncRNA in human cells including their impact in tumorigenesis. Both ESR and ERs improved their skills and utilized them at their original labs after their return, thus increasing the excellence and competitiveness of project partner institutions.
On the other hand, BIOVENDOR, a biotechnology company, led and trained the partners (i) in novel detection approaches for small ncRNAs, but mainly (ii) assay development and validation and CE-IVD certification for new diagnostic products and (iii) better understanding of business-driven research environment and translational perspective and mindset.

Travail effectué depuis le début du projet jusqu’à la fin de la période considérée dans le rapport et principaux résultats atteints jusqu’à présent

Under the framework of WP1, we have achieved a significant milestone by successfully standardizing processes related to detecting small ncRNAs in clinical samples. The approved SOP has been disseminated among the partners and served as a recommended guideline in WPs 3-5, which focused on discovering small ncRNAs as biomarkers in CRC, HCC, and RCC, respectively.
As part of WP2, UMF CLUJ has successfully completed all tasks, including the delivery of D2.1 Exosomal small ncRNA profile from blood plasma/serum samples. Partners from UMF CLUJ evaluated levels of CRC-related miRNAs in the exosomes and confirmed that they are significantly elevated in CRC patients compared to healthy controls. UMF CLUJ also finalized all planned secondments related to WP2, demonstrating successful collaboration within the RNADIAGON consortium.
The scientific progress and results of WP3 were summarized in D3.1: Circulating small ncRNA-based diagnostic signature in CRC patients. As part of WP3, MU collaborated with BioVendor (WP6) on the validation phase of small ncRNA as CRC diagnostics to enable the development of the intended product. A postdoc secondee from MU underwent her secondment focused on analyzing circulating miRNAs in CRC at MDACC and further facilitated works on WP3.
UNIFE accomplished all WP4 tasks, with results summarized in D4.1 and focused publication output. They identified and independently validated serum miRNAs capable of predicting the response to therapy in patients with advanced HCC. The two secondments to MDACC from UNFE facilitated the work on WP4.
MUG has successfully implemented the SOP (WP1) and performed global profiling and validation of circulating miRNA and piRNA levels and identification of specific miRNA and piRNA signatures specific for RCC and each RCC histological subtypes, which is declared in approved D5.1. MUG collaborated with BioVendor to perform independent cross-laboratory validation, whereas one secondment from BioVendor to MUG further facilitated this step.
To fulfil the main objective of WP6, BioVendor has successfully implemented technology for detecting small ncRNA and assembled the prototype diagnostic kit based on detecting two circulating small ncRNAs. Detailed product information is described in the appendix as technical documentation and Instructions for Use for CRC sncRNA diagnostic kit (D6.1).
As a part of W7, training focused on the demonstration of the process of development, production, and certification of diagnostic tests, ensuring continuity leading to a successful transfer, was included in the internships between BioVendor and MUG, UNIFE, UKE, and CLUJ.
To fulfil the aims of the WP8 and to disseminate project results, social media platforms were used to spread knowledge about internships and the possibilities the RISE program could offer. Also, we conducted workshops and project meetings, and interviews with RNADIAGON researchers appeared in print media, online articles, TV, and radio. In total, 24 scientific publications were dedicated to RNADIAGON, many of which were the result of collaborative efforts between partners during secondments. These publications have played a significant role in advancing research in the field.

Progrès au-delà de l’état des connaissances et impact potentiel prévu (y compris l’impact socio-économique et les conséquences sociétales plus larges du projet jusqu’à présent)

The results obtained so far push the boundaries of knowledge in the use of non-coding RNAs as diagnostic markers, especially in cancer, but many of the findings are also applicable in the field of non-cancer diagnostics. A significant contribution to the general application of small non-coding RNAs in clinical practice was especially the standardization of their preanalytical processing and subsequent quantification, which undoubtedly increased the robustness and repeatability of the results obtained. The possibility of wide application of non-coding RNAs in diagnostics is also significantly increased by the results obtained in their detection using ELISA platforms, which is a commonly available technology even in small diagnostic workplaces. Current problems are also the diagnosis from limited amounts of biological material, which cannot be increased without high risk to the patient, and the well-known heterogeneity of cancer, which often leads to underestimation of the diagnosis. In this area, the introduction of experimental workflows allowing combined analysis of microRNA, mRNA, and protein at the single cell level has significantly contributed to the current state of the art.

The significance of this project's impact was that it represented a model project usable for training and translation of other promising results with the potential to be used as diagnostic biomarkers in cancers. Also, from this perspective, the project succeeded, and the prototype of small ncRNA-based CRC diagnostics was successfully developed at BioVendor based on the collaboration of RNADIAGON partners. This aspect of the project can enhance innovation capacity, create new market opportunities, and strengthen the competitiveness and growth of the project’s industrial partner. As colorectal cancer is an important cancer with a high incidence, our project has also contributed to solving a significant societal problem by developing new diagnostics.

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