RNA Technologies and Therapeutics for Neuroscience

May 30-June 6, 2026

Director: Timothy Bredy

University of Queensland, Australia

Faculty:

Gene Yeo, University of California, San Diego, USA

Eric Wang, University of Florida, Gainsville, USA

Piero Carninci, Human Technopole, Milan, Italy

John Mattick, University of New South Wales, Australia

André Fischer, University Medical Center, Göttingen, Germany

Kelly Clemens, University of New South Wales, Sydney, Australia

Timothy Bredy, University of Queensland, Australia

In this Advanced Course, world-leading experts in RNA in neuroscience will discuss emerging RNA technologies for use in foundational research that will establish the basis for understanding RNA in the brain and harness the power of RNA as new medicines for neurological disorders.

RNA is a highly versatile molecule that sits at the epicentre of genetic information. Although it is chemically and structurally similar to DNA, RNA is far more dynamic and capable of many organisational and catalytic activities beyond its role as an intermediate for protein synthesis. For example, in recent years, RNA has been shown to act as a cellular scaffold, to serve as a transporter of cellular cargoes, to guide epigenetic processes, and to regulate gene expression. Notably, many of these processes have now been shown to be critically important for brain function.

Furthermore, with respect to therapeutic potential, because RNA is very small and can be highly stable, and due to its sequence specificity, RNA can be programmed with relative ease. These features endow RNA with the potential to be harnessed as a novel therapeutic ‘device’. Indeed, we are witnessing a virtual explosion in the use of RNA molecules to control many aspects of biology. For example, RNA-guided surveillance complexes have been developed to edit the genome and used to control protein expression and mRNA stability.

The translational value of this approach has been validated by the development of several critical RNA-based medicines, driven by rapid advances in CRISPR-based RNA targeting systems and the creation of synthetic RNAs coupled with lipid-based nanoparticle delivery. Excitingly, RNA-based therapeutics have begun to enter preclinical trials for the treatment of neurological diseases, and the field is rapidly progressing toward the development of new diagnostic tools for brain disorders. By 2030, the estimated market value of RNA technologies and RNA therapeutics is expected to exceed $107 billion (USD).

Andre Fischer

The non-coding RNAome in neurodegenerative diseases: expanding the space for drug discovery and translation

Translational research over the past decades has primarily focused on the protein-coding portion of the genome; hence , genes that are translated into proteins serve specific functions and may become dysregulated in neurodegenerative and neuropsychiatric diseases. However, only about 1.5% of the human genome encodes proteins, while more than 70% is transcribed into non-coding RNAs (ncRNAs), which were long dismissed as “junk.” Today, ncRNAs are increasingly recognized as key regulators of diverse cellular processes.
Over the last decade, our understanding of ncRNA function has been revolutionized, and the field of RNA-based therapeutics is rapidly expanding, with remarkable progress in translating basic findings into clinical applications.
During the lectures, I will provide an overview of current efforts in the field of neurodegenerative and neuropsychiatric diseases to explore ncRNAs as complementary liquid biomarkers. I will also discuss recent projects aimed at targeting ncRNAs as novel therapeutic candidates to intervene in distinct phases of disease progression. The topics will span RNAome analysis in epidemiological and clinical studies as well as molecular biology approaches to understand the role of disease-associated ncRNAs and their molecular functions.

John Mattick

Long noncoding RNAs associated with cognitive traits and disorders

The role of RNA in cell, developmental and neurobiology has been misunderstood for decades, because of the assumption that most genetic information is transacted by proteins. However, it is now apparent that there are hundreds of thousands of other genes that specific small and large regulatory RNAs, the latter known as long noncoding RNAs (lncRNAs). Most, but not all, lncRNAs are the products of genetic loci called enhancers, are highly alternatively spliced, and act as modular scaffolds and guides for the formation of phase-separated nuclear and cytoplasmic domains that mediate the epigenetic regulation of gene expression during differentiation and development, as well as learning in conjunction with RNA modifications that superimpose plasticity on these regulatory networks. LncRNAs show specific cellular expression and subcellular localization patterns in the brain, including at synapses, and many are expressed from genomic regions linked to complex traits and disorders by genome-wide-association studies (GWAS), which generally lack protein-coding sequences. Most neural expressed lncRNAs with validated functions in rodents map to syntenic human loci exhibiting commensurate human cognitive and neuropsychiatric GWAS traits, which are prime candidates for the molecular etiology of these traits. Phenotypic analysis of the developmental effects of lncRNAs can be undertaken by using CRISPR-Cas13 or ASO-mediated knockdown in brain organoid cultures. Mapping rodent orthologs of lncRNAs expressed from regions associated with intelligence, mood disorders and addiction, and their expression patterns (such as in habenula glutamatergic neurons), permits their analysis by proxy with imaging and cognitive and behavioral phenotyping.

Timothy Bredy

RNA technologies for experience-dependent plasticity, learning, and memory

Following the recent rise of RNA as a therapeutic tool and the rapid development of new RNA technologies, it is becoming increasingly clear that the 21st century is the era of RNA. Neuroscience, as a discipline, has a long history of embracing new technologies to advance the understanding of brain function, particularly in relation to learning and memory. I will discuss emerging RNA technologies related to imaging, isolation, identification, and manipulation of RNA in the brain, and discuss their potential to advance the fundamental understanding of how RNA influences experience-dependent plasticity, learning, and memory. Additionally, I focus on how we have applied these technologies to understand how different classes of regulatory RNAs control memory, and how they might be harnessed to treat neurological diseases characterised by cognitive impairment.

Piero Carninci

Genome regulation by non-coding transcription

Less than 2% of the mammalian genome encodes proteins, yet most of it is extensively transcribed into long non-coding RNAs (lncRNAs), enhancer RNAs, and retrotransposon-derived transcripts. How this vast layer of non-coding transcription contributes to genome regulation remains poorly understood. Through the FANTOM6 consortium, we combined cap-trapper full-length RNA sequencing (CFC-seq), RADICL-seq, CAGE, and Hi-C to develop comprehensive RNA–chromatin interaction maps across 16 mammalian cell types and states. These datasets reveal that RNAs form an extensive and structured layer of chromatin organisation, exhibiting both local and long-range interactions that change dynamically during differentiation and activation. We identify lncRNAs, enhancer RNAs, and intronic RNAs that associate with chromatin in cell-specific patterns, many of which may modulate epigenetic states and gene expression. Perturbing selected lncRNAs produces measurable phenotypic effects, emphasising RNA as a fundamental structural and regulatory component of chromatin. Collectively, these findings redefine the non-coding transcriptome as a central determinant of chromatin architecture and cellular identity.

Gene Yeo

RNA-binding proteins in aging and neurodegeneration

Post-transcriptional gene regulation by RNA-binding proteins controls every step of the life cycle of non-coding and coding RNAs, from splicing to translation and mRNA decay. During the lectures, I will present our efforts to understand RNA-binding proteins and their roles in neuronal aging and degeneration. We posit a model in which defects in RNA-binding proteins during aging create vulnerabilities to neurodegenerative diseases such as ALS. I will also present technologies that enable us to study RNA-binding proteins at scale and at single-cell resolution in mammalian brains.

Eric Wang

Repeat expansion diseases cause RNA toxicity in the nucleus and cytoplasm

DNA repeat expansions cause over 60 neurological and neuromuscular diseases, and a key mechanism is gain of toxic RNA function. I will use myotonic dystrophies, a specific class of diseases, to describe how repetitive RNAs sequester RNA-binding proteins, resulting in global changes in alternative splicing and RNA localisation. I will illustrate how a mathematical framework that links RNA-binding protein levels to splicing outcomes is used to measure disease severity and responses to therapeutics currently in clinical trials, such as antisense oligonucleotides. I will further extend this framework into the temporal dimension by describing ethynyl-uridine labelling methods to capture nascent RNAs in vivo, thereby providing predictions of the speed of molecular and phenotypic rescue, depending on the transcripts and pathways in question. Finally, I will discuss how RNA-binding proteins often play dual roles in the nucleus and the cytoplasm, with the latter involving interactions with kinesin motors to transport ribonucleoprotein granules to their final destinations, such as membranes and synapses. Techniques discussed will include proximity labelling approaches, fluorescent in situ hybridisation, massively parallel reporter assays, and mathematical modelling.

Kelly Clemens

Non-coding RNAs for mental disorders

RNA presents a promising therapeutic avenue for cognitive and mental health disorders that remain difficult to treat due to tolerance, poor adherence, or adverse side effects. I will explore how targeting non-coding RNAs (ncRNAs) may offer a more precise approach, particularly in conditions such as addiction, where dysfunction arises within neural circuits that are otherwise essential for normal brain function. In these contexts, subtle modulation of neuronal activity—rather than broad inhibition or excitation—is required. I will also address the key challenges of delivering RNA-based therapeutics to the brain and highlight recent advances that may help overcome these barriers.