Events
21 October 2025
RNA symposium - detailed agenda
October 21st
Progetto Manifattura, Rovereto
Opening Session
17:30 – 18:00
Registration
18:00 – 18:30
Welcome and Introduction to program
Massimiliano Clamer CEO & founder, Immagina Biotechnology | IT
18:30 – 19:15
Keynote: Translating science into Survival
Christoph Huber Co-founder and Deputy Chairman Supervisory Board, BioNTech | DE
19:15 – 19:45
Trentino Sviluppo introduction
Monica Carotta Manager, Trentino Sviluppo | IT
Alessandro Quattrone Professor, University of Trento | IT
19:45 – Late
Social Dinner
October 22nd
Palazzo Benvenuti, Trento
Session 1: The Future of tRNA in Precision Medicine
Chair: Enrico Koenig
08:30 – 09:00
Registration
09:00 – 09:20
Decoding the epitranscriptome at single molecule resolution: towards clinical applications
Eva Maria Novoa Center for Genomic Regulation (CRG) | ES
Abstract +
Transfer RNAs (tRNAs) are the most abundant RNA molecule type in cell types and tissues.
While both tRNA modifications and abundances have been reported to be dysregulated in diverse types of cancer, they remain largely unexplored as potential biomarkers. This is mainly due to the lack of a simple, fast and cost-effective approach to quantify them. In this context, direct RNA nanopore sequencing (DRS) has emerged as a promising technology that can overcome these limitations, as it is in principle capable of mapping all RNA modifications simultaneously, in a quantitative manner, and in full-length native RNA molecules. Our laboratory has recently developed a wet-lab method and accompanying bioinformatic toolkit to sequence native tRNAs using nanopore sequencing (‘Nano-tRNAseq’), which captures both tRNA abundances and modifications with high accuracy, while improving the proportion of recovered tRNA reads compared to using the default nanopore sequencing settings.
Here I will present our latest work on how we can use Nano-tRNAseq for early cancer diagnosis purposes, and thus predict whether a sample is “normal”, “cancerous” or “metastatic” based on its tRNA profiles. Our preliminary results suggest that we can predict whether 96 patient samples are from “normal” or “ cancer” tissues, by just sequencing ~10,000 tRNA molecules per sample, in less than 1hour from starting the sequencing run, with an accuracy greater than 95%, and at a cost of 50€/sample.
09:20 – 09:40
tRNAslation control of eukaryotic gene expression
Sebastian Glatt University of Veterinary Medicine | AT
Abstract +
My research group investigates various mechanisms of translational control that regulate the production of specific protein sets through chemical modifications of tRNA molecules. In cells, all proteins are synthesized by the ribosome, which relies on transfer RNA (tRNA) to decode the genetic information in mRNA and assemble polypeptide chains accordingly. Our lab focuses on uncovering the molecular mechanisms that drive specific base modifications within the anticodon regions of tRNAs. These modifications significantly impact the efficiency and fidelity of codon-anticodon pairing, thereby influencing translational rates and the dynamics of protein folding. Recent studies have revealed that disruptions in these modification pathways are closely linked to the development of certain neurodegenerative diseases and cancers. To investigate these processes, we primarily employ X-ray crystallography (MX) and cryogenic electron microscopy (cryo-EM) to capture high-resolution snapshots of the macromolecular complexes involved and to visualize reaction intermediates at the atomic level. We complement these structural approaches with a variety of in vitro and in vivo methods to validate and interrogate our findings. In addition to our core focus, we have begun exploring other (t)RNA modification pathways and are now using cryo-EM to directly resolve the structures of folded RNA molecules. We also aim to elucidate how post-transcriptional modifications influence ribosomal decoding and translation elongation by directly imaging translating ribosomes at atomic resolution. Finally, we are developing new structural, biochemical, and biophysical techniques to study structured RNA domains. In summary, our research advances the fundamental understanding of eukaryotic gene expression and its intricate regulatory mechanisms.
09:40 – 10:00
Extracellular nicked tRNAs: a new biomarker type for the liquid biopsy era
Juan Pablo Tosar B4-RNA | UY
Abstract +
Circulating nucleic acids, including cell-free DNA (cfDNA) and RNA (cfRNA), are promising minimally invasive biomarkers for early cancer detection. Detecting circulating tumor DNA (ctDNA) in plasma or serum is feasible but requires deep sequencing, since tumor DNA closely resembles DNA from healthy cells. cfDNA methylation and fragmentation patterns provide additional information but show limited sensitivity at early cancer stages. RNA, in contrast, offers amplification and quantitative advantages, as each gene can be expressed in thousands of copies per cell, and RNA profiles are often cell type–specific. However, RNA is prone to degradation by extracellular RNases, which are highly active in blood. It is commonly assumed that cfRNA is protected within extracellular vesicles (EVs), but most cfRNAs are actually found outside EVs, raising questions about their stability. Our group has shown that these stable nonvesicular cfRNAs are primarily “nicked tRNAs” (i.e., tRNAs released into the extracellular space and processed by RNases into structurally discontinuous yet stable molecules). These nicked tRNAs are abundant, diverse, and readily detectable by next-generation sequencing (NGS) even at low depth. Their sequence diversity enables powerful AI-based classification approaches, and their dysregulation in cancer provides a strong biological rationale for studying them in blood. To address their fragmented nature, we developed REJOIN-seq, a sequencing method that repairs nicked tRNAs before sequencing. REJOIN-seq achieves sub-isodecoder resolution and detects RNA modifications, offering a robust platform for RNA-based liquid biopsies in cancer screening and monitoring.
10:00 – 10:15
At-line IVT reaction monitoring and purification improves yield and purity of tRNA
Rok Sekirnik Sartorius BIA Separations | SI
Abstract +
Abstract forthcoming.
10:15 – 10:25
The tRNA-modifying enzyme QTGAL maintains translational fidelity to support breast cancer cell proliferation and migration
Adriano Setti University of Rome “La Sapienza” | IT
Abstract +
Modifications at the wobble position of tRNAs are critical for accurate codon recognition during translation elongation and play a central role in preserving proteome integrity. Queuosine-tRNA galactosyltransferase (QTGAL), an enzyme that catalyzes the galactosylation of queuosine (Q) at wobble position of tRNA-Tyr, is frequently upregulated in breast cancer. Here, we demonstrate that QTGAL downregulation in triple-negative breast cancer (TNBC) cell lines significantly impairs both cell proliferation and motility. Ribosome profiling and dual-luciferase reporter assays reveal that loss of QTGAL function leads to increased translational readthrough and amino acid misincorporation. These defects in decoding fidelity result in aberrant C-terminal protein extensions and widespread amino acid substitutions across the proteome. Our findings uncover a previously unrecognized role for QTGAL in maintaining translational accuracy and highlight how its loss induces proteotoxic stress with cytotoxic effects in TNBC cells.
10:25 – 11:00
Coffee Break ☕
Session 2: Targeted Therapies, Translation and Clinical Impact
Chair: Lutz Kirchrath
11:00 – 11:20
Rapid isolation of ribosomes and translational machinery for structural, functional, and clinical applications
Jessey Erath Brown University | US
Abstract +
Ribosomes are RNA-protein complexes essential for protein synthesis and quality control. Traditional methods for ribosome isolation are labor-intensive, expensive, and require a substantial amount of starting biological material. In contrast, our method, RNA affinity purification using poly-lysine (RAPPL), provides a rapid, simple, and cost-effective alternative applicable to a wide variety of organisms and material types (cell lysates, whole cells, organs, or whole organisms). We have also demonstrated its compatibility with traditional isolation techniques, as well as downstream biochemical and structural applications. We also significantly improve upon an existing method with RAPPL-RiboSeq, producing a 30-50 fold increase of input RNA leading to improved read counts in even lowly expressed genes. By significantly reducing the amount of the starting biological material – as well as material recovery – and the time required for isolation, RAPPL has the potential to facilitate the study of ribosomal function, interactions, antibiotic resistance, and more thereby providing a versatile platform for academic, clinical, and industrial research.
11:20 – 11:40
Transforming Autoimmune Disease Treatment with First-in-Class Antigen-Drug Conjugates (AgDCs)
Kfir Oved Canopy Immuno-Therapeutics | IL
Abstract +
Antigen-drug conjugates (AgDCs), developed by Canopy Immuno-Therapeutics, represent a next-generation strategy for precision treatment of antibody-mediated autoimmune diseases. Contrary to traditional immunosuppression that broadly dampen immune responses and risk infection or other complications, AgDCs exhibit exquisite antigen specificity, eliminating only the pathogenic immune components responsible for disease. By conjugating disease-specific antigens with an inhibitory Fc, and a targeted cytotoxic agent, these novel biologics achieve a highly selective clearance of the autoreactive B cells and the pathological antibodies, preserving the patient’s overall immune competence. This targeted approach is paving the way toward potentially curative, non-immunosuppressive therapies in a variety of autoimmune indications.
11:40 – 12:00
tRNA fragments as new biomarkers for early and non-invasive detection of skin cancer
Alessia Del Piano Immagina Biotechnology s.r.l. | IT
Abstract +
tRNA-derived fragments (tRFs) are generated by specific nuclease cleavage events, leaving characteristic post-transcriptional modifications at their 3′ ends. These biochemical signatures make tRFs highly stable and biologically distinct, offering strong potential as molecular biomarkers. In this study, we explored the clinical relevance of a subset of tRFs in cutaneous squamous cell carcinoma (cSCC), a common skin cancer where early detection and non-invasive biomarkers remain limited. To support this research, we developed DOORs, a platform that integrates NGS-based profiling, AI-driven bioinformatics, RNA-based design, and targeted 3′P-qPCR validation, enabling precise characterization of modified RNA fragments. Using DOORs, we identified a panel of tRFs consistently present in primary cSCC cell lines, tissues, and plasma and differentially detected in healthy versus the disease state, supporting their potential as minimally invasive liquid biopsy markers. Our findings reveal a connection among three dimensional aspects: tRNA fragmentation, full-length tRNA abundance and altered tRNA modifications, suggesting a dysregulated tRNA processing in cSCC biology. Together, our results identify a panel of clinically relevant biomarkers and introduce a unique platform for their future assessment.
12:00 – 12:45
Panel discussion: The future of personalized therapies
Moderator:
Neil Kubica General Inception | US
Panelists:
Paolo Ascierto Istituto Nazionale Tumori “G. Pascale” | IT
Juan Pablo Tosar B4-RNA | UY
Carlos Palma B4-RNA | UY
Kfir Oved Canopy Immuno-Therapeutics | IL
12:45 – 14:15
Networking lunch break 🍽️
14:15 – 14:25
Cancer diagnostics based on ribosome quality control vulnerability
Rastislav Horos Hummingbird Diagnostics GmbH | DE
Abstract +
Uncontrolled growth and proliferation of cancer cells puts a high demand on protein synthesis apparatus. To cope with it, cancer cells upregulate ribosome synthesis and tune the translation in favor for high output rates. High translation rates however can lead to effects such as ribosome slowing and stalling on mRNA (e.g. due to the limiting tRNA availability) and inevitably ribosome collisions. Ribosome stalling and collisions cause the activation of ribosome quality control (RQC) response that can lead to – for cancer cells – undesired outcomes such as ribotoxic death. Yet, cancer cells can upregulate or even exploit RQC, not only for the sake of protein synthesis demands, but also to cope with chemotherapy agents. As is being increasingly clear, chemotherapies, too, evoke strong ribotoxic stress response and upregulated RQC poses a problem for first-line therapies used for advanced and metastatic cancers. Previously, we reported the usage of 28S rRNA fragment (“miLung#1”) for lung cancer diagnostics using liquid biopsy. Since then, we uncovered the intimate connection of miLung#1 to RQC and show that ribotoxic stress response leads to miLung#1 production and secretion to extracellular environment. We identified molecular pre-requisites of miLung#1 production and further delineated its stability in extracellular environment and liquid biopsy devices. Finally, using data from late-stage lung cancer patients we show that miLung#1 biomarker has also prognostic value independent on tumor subtype or its mutational profile. Finally, we discuss the usage of miLung#1 to identify cancer patients with exposed RQC vulnerability for improved therapy response and precision medicine.
14:25 – 14:45
Regulation of the rate of protein synthesis at termination: a new therapeutic target?
Stefano Biffo INGM, Fondazione Romeo ed Enrica Invernizzi & University of Milan | IT
Abstract +
Translation is made of initiation, elongation and termination. The role of termination in relaying extracellular outputs to the translation machinery is unknown. We show that the controlled recycling of ribosomes post-termination is a major checkpoint that integrates mitogenic signals and antiviral responses. In detail, recycling of ribosomes at stop codons, maximal translation and cellular proliferation strictly depend on eIF6 phosphorylation, both in vitro and in vivo. Lack of eIF6 phosphorylation, as observed during viral infection or prolonged starving, causes accumulation of ribosomes at stop codons and a massive translational remodeling. The outcome is a cellular status that we named RESt, for Reversible Energetic Stop. RESt is marked by pro-survival and pro-inflammatory NF-kB signalling and a switch to respiration. Acute RESt is rescued by eIF6 phoshorylation, but chronic RESt in vivo leads to senescence. Thus, the recycling rate of ribosomes post-termination is a physiologically controlled event impacting initiation.
14:45 – 15:05
Translational Fidelity
Jody Puglisi Stanford University School of Medicine | US
Abstract +
Abstract forthcoming.
15:05 – 15:25
Simultaneous detection of eight modifications on single RNA molecules using nanopore direct RNA sequencing
Angelica Vittori Oxford Nanopore Technologies plc. | UK
Abstract +
Abstract forthcoming.
15:25 – 15:35
Subcellular spatial transcriptomics of motor neurons for the identification of local therapeutic targets for ALS linked to mutations in FUS
Diana Piol University of Padova | IT
Abstract +
Motor neurons are highly polarized cells in which local translation plays a fundamental role in the maintenance of their long axons. One of the earliest events occurring in amyotrophic lateral sclerosis (ALS) is the denervation of the neuromuscular junctions (NMJs), which suggests that local events may be valuable as therapeutic approach. We identified suppression in axonal translation as an early feature of ALS mice expressing the full-length human FUS gene harboring ALS-causing mutations, suggesting that disruption of local protein synthesis may underlie the early axonal/NMJ demise observed in ALS. In this project, we aimed to unravel the transcriptional signature of motor neuron cell bodies in the mouse spinal cord and their respective axons in the adult sciatic nerves in healthy and mutant FUS animals for the identification of early molecular players in the maintenance of mature axons and their dysregulation in ALS. Cutting-edge spatial transcriptomics approaches, including untargeted barcoded and targeted multiplexed single molecule fluorescence in situ hybridization technologies, were applied to 12-month-old mouse spinal cord and sciatic nerve sections. We discovered that FUS mutation disrupts the compartment-specific RNA signatures including components of the translation machinery. In particular, an eukaryotic initiation factor, critical for protein synthesis regulation, is found to be locally impaired in axons. Targeting its axonal activation, we show rescue of the axonal translation defects and an amelioration of the neuronal functional deficits provoked by ALS-causing FUS mutation. Our findings provide critical novel mechanistic insights into compartment-specific toxic pathways that may advance future therapeutic development to treat ALS.
Session 3: Value creation session — from the lab bench to the market
Chair: Davide Merulla
15:35 – 15:50
RNA Druggability Mapping With Multimodal AI
Dalya Gartzman Renasis Bio | IL
Abstract +
Small molecules hold great promise for modulating the RNA life cycle, yet only one has been approved to date. At Renasis Bio, we aim to expand this space by systematically identifying RNA pockets suitable for small molecule intervention. To do so, we are building an AI-driven platform that integrates multi-layered RNA biology data to uncover features of such druggable pockets. These predictions are tested in the lab and used to train models in a continuous feedback loop - transforming existing data into new biological insights. In this talk, I’ll share how multimodal data and AI, grounded in rigorous science and wet-lab validation, can uncover novel regulatory pockets in RNA - shaping a new path for small molecule discovery.
15:50 – 16:05
BrightMol Biotech: shining light on biotech innovation with LIPS technology
Ilaria Zeni BrightMol Biotech | IT
Abstract +
I will present the journey from academic proof of concept to a biotech platform ready to expand into multiple therapeutic areas. At BrightMol Biotech, we are tackling drug discovery through phenotypic screening using our proprietary LIPS (Light Identification of Protein Suppressors) technology, a high-content, imaging-based platform designed to accelerate the identification of small molecules and genetic modulators that influence protein expression. Originally developed and validated in the context of prion diseases, in which misfolded prion protein (PrP) drives fatal neurodegeneration, the LIPS platform enables the rapid, quantitative assessment of changes in protein levels in live-cell environments with high sensitivity and spatial resolution. Our initial studies using LIPS-PrPER, a version targeting the endoplasmic reticulum, have identified small molecules, such as cardiac glycosides, that suppress PrP expression. These findings are now being explored in ongoing translational studies. Notably, the activity of a recently developed PrP degrader from the biotech industry has also been validated using LIPS. The LIPS framework is highly adaptable: beyond PrP, it has already been extended to monitor other proteins implicated in neurodegenerative and systemic diseases, including α-synuclein and AKT. At BrightMol Biotech, our mission is to enhance and accelerate drug discovery by enabling the identification of therapeutically relevant modulators in a time- and cost-efficient manner
16:05 – 16:30
Coffee Break ☕
16:30 – 16:45
What if, we could redesign the innovation map in genome-editing technologies, accelerating access to life-saving therapies.
Letizia Goretti Alia Therapeutics | IT
Abstract +
Redefining the Future of Genome Editing Technologies in Europe, starting from Italy.
The CRISPR-based genome editing sector is rapidly evolving, with technologies like base editing and prime editing enhancing precision and effectiveness for human therapeutic applications. There is also growing interest in innovative systems for safe genomic integration, essential for advanced gene replacement or repair. Numerous CRISPR-based therapeutic approaches are progressing through clinical validation, mainly led by U.S. and Chinese companies. In response to this therapeutic potential, regulatory agencies are updating guidelines to support the development of genome editing therapies more efficiently, especially for rare genetic diseases. Despite the sector's dynamism, Europe is lagging behind U.S. and China in innovation, investment, and industrial leadership in genome editing technologies. Founded in 2018, Alia Tx is one of two EU-based companies advancing CRISPR genome editing discovery and development capabilities at industrial scale. The human microbiome is not only the source platform for the discovery of novel genome editing tools, but also a highly complex and largely unexplored commensal ecosystem. Increasing evidence links microbiome composition and microbial health to a wide range of diseases, including serious conditions such as microbial infections, cancer recurrence, and autoimmune disorders. The Dolomitic Discovery Alliance (DDA) is stemming from the strategic alliance between Alia Therapeutics, the first and only Italian company specialized in CRISPR-based genome editing, and Prebiomics, a leader in AI-supported metagenomic microbiome analysis. The DDA aims to revolutionize the discovery, development, and distribution of next-generation genome editing tools for selective and safe therapeutic applications and beyond.
16:45 – 17:00
The RNA Market Race: Winning with Differentiation Beyond the Science
Shweta Srivastava Biomartech | IN
Abstract +
Abstract forthcoming.
17:00 – 18:00
Panel discussion: Big Pharma & RNA Startups — Build, Buy or Co-create?
Moderator:
Gabriella Viero Institute of Biophysics | IT
Panelists:
Akcan Istif Scientifica Venture Capital | IT
Elita Montanari EVis Bioscience | CH
Neil Kubica General Inception | US
Letizia Goretti Alia Therapeutics | IT
Kfir Oved Canopy Immuno-Therapeutics | IL
Dalya Gartzman Renasis Bio | IL
Dor Arieli Renasis Bio | IL
18:00 – 18:45
Closing Keynote lecture: Technology at the cutting edge: realising new opportunities for nanopores
Hagan Bayley Professor of Chemical Biology, University of Oxford | UK
Abstract +
Abstract forthcoming.
18:45 – 19:00
Short closing remarks
19:00 – 20:30
Networking aperitif & Poster session