Development of antiviral RNA therapeutics targeting SARS-CoV-2 infection

Project Member(s): Johansen, M., Hansbro, P.

Funding or Partner Organisation: Medical Research Future Fund (MRFF Coronovirus Scheme)
Medical Research Future Fund (MRFF Coronovirus Scheme)

Start year: 2022

Summary: The COVID-19 pandemic remains a significant global health threat. Vaccines have provided some protection, however this relies on robust immune responses and SARS-CoV-2 is evolving vaccine resistance. Direct antiviral treatments, that do not require immune responses, are urgently needed to treat vaccine resistant variants and to protect ~20% of the global population with impaired immunity. Further, recent data suggest antiviral treatments need to be delivered early and therefore must be simple to give. Our innovative approach addresses these problems with antiviral RNA therapeutics that specifically target invariant regions of human coronaviruses delivered by nanoparticle inhalation directly to the respiratory tract. We have identified a suite of antiviral siRNAs that effectively suppress all SARS-CoV-2 variants and other human coronaviruses in vitro. We have an established team of experts in virology, antiviral RNA design, nanotechnology, RNA-nanoparticle production (NSW-RPRN), respiratory delivery devices and COVID-19 mouse models to allow preclinical testing of these potential therapies. Following optimisation of RNA-nanoparticle formulations, we will perform standardised biodistribution studies following their administration to the respiratory tree. Finally, we will perform proof of concept studies using an ACE2 transgenic mouse model of COVID-19 infection to generate in vivo preclinical safety and efficacy data required for translation to human proof of concept clinical trials. Optimisation of RNA-nanoparticle platforms will provide a safe and effective delivery system for antiviral RNA for COVID-19 disease. This delivery system will be adaptable for antiviral RNAs targeting other respiratory infections. The project outcome will be accelerated development of antiviral RNA therapeutics to prevent progressive SARS-CoV-2 infection, which will reduce COVID-19 disease burden, benefiting Australian and global populations and enabling preparedness for emerging viruses.

FOR Codes: Biochemistry and cell biology not elsewhere classified , Infectious agents, Prevention of human diseases and conditions, Treatment of human diseases and conditions

Acknowledgement of Country

UTS acknowledges the Gadigal people of the Eora Nation, the Boorooberongal people of the Dharug Nation, the Bidiagal people and the Gamaygal people, upon whose ancestral lands our university stands. We would also like to pay respect to the Elders both past and present, acknowledging them as the traditional custodians of knowledge for these lands.