Researchers at the Kirby Institute at UNSW Sydney are developing a new antiviral approach that could help protect against COVID-19 and potentially other respiratory viruses. The work, led by A/Prof Chantelle Ahlenstiel, explores the use of short interfering RNA (siRNA) therapeutics delivered through an intranasal spray.

Unlike vaccines that train the immune system to recognise a virus, siRNA therapeutics work by directly targeting viral genetic material. These short RNA sequences are designed to match specific regions of a virus and trigger the degradation of its messenger RNA, preventing the virus from producing the proteins it needs to replicate.

The team has developed a formulation that combines three key components: a carefully designed siRNA sequence, a lipid nanoparticle (LNP) that protects and delivers the RNA, and an intranasal spray device that enables simple self-administration. Delivered directly through the nasal passages, the therapy aims to reduce viral activity in the respiratory tract, the primary entry point for many respiratory viruses.

Early pre-clinical studies in mouse models have shown promising results, with the treatment reducing viral RNA levels and improving clinical outcomes. The researchers are now exploring how the platform could be adapted for a broader range of respiratory viruses, including influenza and RSV.

A platform for pandemic preparedness

A key feature of the project is the design of highly conserved siRNA sequences that target viral regions shared across multiple coronavirus strains. By focusing on stable parts of the virus genome, the approach may remain effective even as viruses evolve.

This strategy offers potential advantages for pandemic preparedness, allowing researchers to rapidly adapt the platform to emerging viral threats.

The work is the result of a large multidisciplinary collaboration involving universities, research institutes and international industry partners. Together, the team has developed a platform technology, combining RNA design, nanoparticle delivery and intranasal administration, that could be applied to multiple respiratory pathogens.

Enabling research through open access infrastructure

Open access research infrastructure has played an important role in advancing this work. The UNSW RNA Institute provides specialised capabilities for RNA therapeutic development, including synthesis and quality control of RNA molecules.

The institute is expanding Australia’s capabilities in RNA therapeutics manufacturing and pre-clinical development. The facility also acts as a key entry point into the NSW RNA ecosystem, supporting researchers and industry partners working in RNA-based therapeutics.

Through this work, the institute synthesised the siRNA molecules used in the project using a quality-assured, scalable process. Access to this capability has helped enable the progression of the research toward potential clinical translation.

As highlighted in this case study, open access research infrastructure plays an important role in supporting the development of new antiviral therapeutics and strengthening Australia’s preparedness for future health challenges.