Project Details
Description
NSW-RRTN Project
MQ led project where UNSW is the admin org and is also collaborating on the project.
Influenza continues to pose a significant global health burden, with seasonal epidemics leading to hundreds of thousands of deaths annually and periodic pandemics causing substantial socioeconomic disruption. Although vaccines remain the cornerstone of influenza prevention, their effectiveness varies by season and strain, and uptake is often limited. Moreover, antiviral drugs are only partially effective and must be administered early in the infection cycle. To address this, our project proposes a transformative approach to influenza therapy using RNA interference (RNAi) via small interfering RNA (siRNA) therapeutics. This project builds upon the substantial progress made under the NSW Respiratory Pandemic Response Network (NSW-RPRN, 2021–2025), which developed an intranasally administered lipid nanoparticle (LNP)-encapsulated siRNA therapy for SARS-CoV-2.
Our new initiative will adapt and expand this design pipeline to target influenza A and B viruses. Using advanced bioinformatic tools and cross-strain sequence alignment, we will identify highly conserved genetic regions across multiple influenza strains to design a library of antiviral siRNAs. These siRNAs will be encapsulated in optimized LNPs, engineered for stability, mucosal penetration, and minimal cytotoxicity. LNPs provide protection from nuclease degradation and facilitate endosomal escape, thereby improving the pharmacokinetics and intracellular delivery of siRNAs.
To ensure effective delivery and clinical scalability, we will employ a Soft Mist Inhaler (SMI) platform to administer the siRNA-LNP formulation intranasally. SMIs are user-friendly, commercially available, and deliver medication as a slow-moving aerosol, making them ideal for targeting the upper respiratory tract. This delivery method also engages the nasal-associated lymphoid tissue (NALT), which plays a key role in both mucosal and systemic immune responses, potentially enhancing the therapeutic efficacy of the siRNA product.
The project will proceed in two stages. The first 12 months will focus on in silico design and in vitro screening of antiviral siRNAs and characterization of their encapsulated LNPs in human airway epithelial cell lines. In the second year, lead candidates will undergo preclinical evaluation in a mouse model of influenza infection. Parallel studies will examine aerosol characteristics, deposition profiles, and bioavailability of the formulation using air-liquid interface (ALI) cell cultures and mechanical nasal and pulmonary models developed by our team.
This initiative brings together leading researchers from Macquarie University, the Woolcock Institute of Medical Research, UNSW, the Kirby Institute, and the Centenary Institute, ensuring multidisciplinary expertise in drug delivery, infectious disease, immunology, and respiratory science. The ultimate objective is to establish a safe, effective, and broadly applicable antiviral therapeutic that can be deployed rapidly in both seasonal and pandemic contexts.
MQ led project where UNSW is the admin org and is also collaborating on the project.
Influenza continues to pose a significant global health burden, with seasonal epidemics leading to hundreds of thousands of deaths annually and periodic pandemics causing substantial socioeconomic disruption. Although vaccines remain the cornerstone of influenza prevention, their effectiveness varies by season and strain, and uptake is often limited. Moreover, antiviral drugs are only partially effective and must be administered early in the infection cycle. To address this, our project proposes a transformative approach to influenza therapy using RNA interference (RNAi) via small interfering RNA (siRNA) therapeutics. This project builds upon the substantial progress made under the NSW Respiratory Pandemic Response Network (NSW-RPRN, 2021–2025), which developed an intranasally administered lipid nanoparticle (LNP)-encapsulated siRNA therapy for SARS-CoV-2.
Our new initiative will adapt and expand this design pipeline to target influenza A and B viruses. Using advanced bioinformatic tools and cross-strain sequence alignment, we will identify highly conserved genetic regions across multiple influenza strains to design a library of antiviral siRNAs. These siRNAs will be encapsulated in optimized LNPs, engineered for stability, mucosal penetration, and minimal cytotoxicity. LNPs provide protection from nuclease degradation and facilitate endosomal escape, thereby improving the pharmacokinetics and intracellular delivery of siRNAs.
To ensure effective delivery and clinical scalability, we will employ a Soft Mist Inhaler (SMI) platform to administer the siRNA-LNP formulation intranasally. SMIs are user-friendly, commercially available, and deliver medication as a slow-moving aerosol, making them ideal for targeting the upper respiratory tract. This delivery method also engages the nasal-associated lymphoid tissue (NALT), which plays a key role in both mucosal and systemic immune responses, potentially enhancing the therapeutic efficacy of the siRNA product.
The project will proceed in two stages. The first 12 months will focus on in silico design and in vitro screening of antiviral siRNAs and characterization of their encapsulated LNPs in human airway epithelial cell lines. In the second year, lead candidates will undergo preclinical evaluation in a mouse model of influenza infection. Parallel studies will examine aerosol characteristics, deposition profiles, and bioavailability of the formulation using air-liquid interface (ALI) cell cultures and mechanical nasal and pulmonary models developed by our team.
This initiative brings together leading researchers from Macquarie University, the Woolcock Institute of Medical Research, UNSW, the Kirby Institute, and the Centenary Institute, ensuring multidisciplinary expertise in drug delivery, infectious disease, immunology, and respiratory science. The ultimate objective is to establish a safe, effective, and broadly applicable antiviral therapeutic that can be deployed rapidly in both seasonal and pandemic contexts.
| Status | Active |
|---|---|
| Effective start/end date | 1/07/25 → 15/02/28 |