The new world of RNA diagnostics and therapeutics

Abstract

The 5th Workshop IRE on Translational Oncology was held in Rome (Italy) on 27–28 March at the IRCCS Regina Elena National Cancer Institute. This meeting entitled “The New World of RNA diagnostics and therapeutics” highlightes the significant progress in the RNA field made over the last years. Research moved from pure discovery towards the development of diagnostic biomarkers or RNA-base targeted therapies seeking validation in several clinical trials. Non-coding RNAs in particular have been the focus of this workshop due to their unique properties that make them attractive tools for the diagnosis and therapy of cancer.This report collected the presentations of many scientists from different institutions that discussed recent oncology research providing an excellent overview and representative examples for each possible application of RNA as biomarker, for therapy or to increase the number of patients that can benefit from precision oncology treatment.In particular, the meeting specifically emphasized two key features of RNA applications: RNA diagnostic (Blandino, Palcau, Sestito, Díaz Méndez, Cappelletto, Pulito, Monteonofrio, Calin, Sozzi, Cheong) and RNA therapeutics (Dinami, Marcia, Anastasiadou, Ryan, Fattore, Regazzo, Loria, Aharonov).

Epstein-Barr virus–encoded EBNA2 downregulates ICOSL by inducing miR-24 in B-cell lymphoma

“…A proposed model underscoring the use of PD-L1, targeting miR-34a mimics as suggested by our previous data 38 in combination with anti–miR-24 molecules to reconstitute ICOSL as an RNA-based immunotherapeutic approach (created with BioRender.com ). Panel E is reproduced from Blandino et al, 56 licensed under a Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ ). …”

Microfluidic Device-Based Virus Detection and Quantification in Future Diagnostic Research: Lessons from the COVID-19 Pandemic

“…One such example of successful commercialization is found in the RNA-based early-cancer diagnostic field, namely GASTROClear DX [80]. GASTROClear DX is a miRNA-based assay that serves as the world's first molecular blood test for early detection of gastric cancer (GC) within susceptible populations [80,81]. The release of GASTROClear DX in 2020 allowed for the risk assessment of GC in seemingly healthy asymptomatic people while simultaneously provided a notable accuracy of 87% higher than any other conventionally quantified blood biomarker for GC such as serum pepsinogen, CEA, and CA19-9 tumor markers [80,81].…”

“…GASTROClear DX is a miRNA-based assay that serves as the world's first molecular blood test for early detection of gastric cancer (GC) within susceptible populations [80,81]. The release of GASTROClear DX in 2020 allowed for the risk assessment of GC in seemingly healthy asymptomatic people while simultaneously provided a notable accuracy of 87% higher than any other conventionally quantified blood biomarker for GC such as serum pepsinogen, CEA, and CA19-9 tumor markers [80,81]. This test is now CE-marked and Singapore Health Science Authority-approved Class C in vitro diagnostics (IVD) permitting commercial availability in Singapore and the ASEAN region along with registration trials in China and Japan [81].…”

“…The release of GASTROClear DX in 2020 allowed for the risk assessment of GC in seemingly healthy asymptomatic people while simultaneously provided a notable accuracy of 87% higher than any other conventionally quantified blood biomarker for GC such as serum pepsinogen, CEA, and CA19-9 tumor markers [80,81]. This test is now CE-marked and Singapore Health Science Authority-approved Class C in vitro diagnostics (IVD) permitting commercial availability in Singapore and the ASEAN region along with registration trials in China and Japan [81]. The development of GASTROClear DX and other novel cancer diagnostic methods such as RNA disruption assays not only highlight the necessity of novel diagnostic means but also the potential of RNA-based systems when they are manufactured at a commercial level.…”

“…Most of the current RNA-based detection methods, shown in the recent literature, demonstrate the numerous benefits of this technology, such as the higher modularity, increased limit of detection, and test turnaround times [73][74][75][76][77]. However, these advancements were not achieved without overcoming some inherent limitations to RNA-based detection, such as the instability and innate reactiveness of exposed RNA in solution [40,42,81,83]. The 2 hydroxyl group found in RNA increases the likeliness of this type of genetic material to be more prone to dehydration and degradation, therefore, making it a historically poor target for genetic probing in vivo, as many DNA and RNA nucleases exist in commonly used diagnostic sample mediums such as blood, saliva, and nasopharyngeal liquid [22][23][24][25].…”