New CRE for Nucleic Acid Sensing boosts RNA therapeutics

30 August 2024

By Rob Clancy, staff writer. Reviewed by Professor Carl Walkley

Dr Natalia Sampaio, Professor Carl Walkley, Dr Sophia Davidson, Professor Seth Masters, Associate Professor Michael Gantier head up the Nucleic Acid Sensing CRE — L-R: L-R: Dr Natalia Sampaio, Professor Carl Walkley, Dr Sophia Davidson, Professor Seth Masters, Associate Professor Michael Gantier

The frontline of defences against viruses and other pathogens will be fortified by the creation of a new Centre of Research Excellence for Nucleic Acid Sensing.

Located in Melbourne at Hudson Institute of Medical Research, the new Centre of Research Excellence (CRE) aims to make the first important steps toward new treatment strategies for a range of auto-inflammatory diseases.

Lead researcher, Professor Carl Walkley, explained that the new CRE will bring together the nation’s foremost Nucleic Acid Sensing experts, spanning fundamental research, preclinical modelling and therapeutics, patient derived cell models and clinician researchers.

Knowledge of RNA sensing pathways

Nucleic acid sensing pathways are the cells’ frontline defence against infection from a range of DNA and RNA containing pathogens, particularly viruses.

When activated, the body responds to fight the infection. Knowledge of this response, particularly RNA sensing pathways, is central to the efficacy and rapid development of new treatments such as RNA therapeutics.

Accelerating knowledge of nucleic acid sensing

Prof Walkley believes that research in this area has reached the point where sharing resources, building knowledge through exchanges and engaging clinical and patient input can synergise to accelerate the research to preclinical testing and ultimately improved patient outcomes.

“To date our ability to do this has been limited by working in different arenas with sporadic overlap. Over the last few years, we have actively become more co-ordinated, interconnected and focussed on leveraging our expertise to rapidly accelerate research in this area“.

Prof Walkley said: “We hope to greatly accelerate knowledge gain in an area that will be foundational for future therapeutics and treatments for both common inflammatory disorders and rare, presently intractable, diseases.”

Prof Walkley’s RNA Biology and Innate Immune Sensing Research Group is located in Hudson Institute’s Centre for Innate Immunity and Infectious Diseases (CiiiD).

Nucleic acid sensing explained

“Our cells have sensors that scan the cell for foreign nucleic acid (DNA/RNA) and react when they encounter it. This is key to protecting us from virus infections. Mutations can cause the sensors to react to the cell’s own DNA and RNA, causing inflammatory disease. In this Centre, we will study how and what the sensors are detecting, if this can be modified, how the sensors co-ordinate a response and apply this knowledge to provide treatment strategies for a range of auto-inflammatory diseases.” Prof Carl Walkley.

Facts

Antiviral Defence Mechanism: Nucleic acid sensing plays a crucial role in detecting pathogen-associated nucleic acids during viral infections. Membrane-bound and intracellular receptors, known as pattern recognition receptors (PRRs), recognise these nucleic acids and trigger innate immune responses to eliminate infections.
Tumour Immunotherapy and Gene Therapies: Nucleic acid sensing is essential for tumour immunotherapy and gene therapies. It supports genetically engineered immune cells or therapeutic nucleic acids in targeting cancer and infectious diseases. Immune cells rely on nucleic acid sensing to prime desirable immune responses during tumour treatment.
Regulation of Gene Therapy: Recent studies have shown that nucleic acid sensing affects the efficiency of gene therapy by inhibiting translation. Understanding these mechanisms is crucial for optimising therapeutic efficacy.
Therapeutic Strategies: Suppression of innate immunity induced by nucleic acid sensing can be achieved through small-molecule inhibitors, virus-derived proteins, and chemical modifications. These strategies offer potential therapeutic approaches for various diseases.
Application in Therapy: Nucleic acid sensing provides insights for developing therapeutic interventions. Researchers explore its impact on immune responses, gene therapies and antiviral defence mechanisms, making it a promising area for medical research.

Collaborators | John Curtin School of Medical Research, Australian National University, University of Melbourne, Murdoch Children’s Research Institute, Royal Children’s Hospital

This research was supported by | National Health and Medical Research Council (NHMRC)