Airway Epithelial Cell-Targeting Nanoparticles to Harness RNA Interference Therapeutics for Respiratory Virus Induced Diseases
Closing Date: 01 July 2021Apply Now
We have developed novel polymer hybrid nanoparticles that specifically target airway epithelial cells. These will delivery respiratory virus RNA targeting siRNAs to specifically degrade viral RNA, halt replication and, in vivo, prevent respiratory virus-induced diseases.
Overarching aim: To determine if NP-mediated, epithelial targeted delivery of small interfering RNA (siRNA) targeting rhinovirus and human coronavirus RNA to:
i) differentiated human bronchial epithelium (in vitro) and
ii) respiratory mucosa (in vivo) inhibits virus replication and virus-induced inflammation and associated respiratory disease.
Airway epithelial cell targeting nanoparticles that harness RNA interference to prevent rhinovirus induced diseases Respiratory viruses such as rhinovirus (RV), coronaviruses and influenza cause a spectrum of clinically significant respiratory diseases ranging from the common cold to exacerbations of chronic respiratory diseases, bronchiolitis and pneumonia. Over 160 RV subtypes have been identified – this represents huge antigenic diversity and an immense challenge (yet to be overcome) for vaccine design.
Novel, pandemic coronaviruses represent an ongoing cause of severe respiratory illness. Endemic coronaviruses are also clinically important and are second behind rhinovirus in causing cold/flu-like illnesses. This number and diversity of respiratory viruses are why we remain susceptible to infections throughout life. Those with a suppressed immune system (eg the very young, old, chronic disease, transplant recipients etc) are particularly at risk of serious illness and death caused by RV infections. An effective treatment for rhinovirus and coronavirus infections would have huge impact on human health globally - despite years of intensive research there is still no anti-viral drug to combat this virus.
RNA interference as an anti-viral approach for respiratory virus infections RNA interference (RNAi) is a potent strategy to induce therapeutic effects in a highly precise manner, which has the potential to change the landscape of medicine and represents a new approach to drug discovery and development.
The prospect of RNAi therapy is extremely exciting following the approval of first RNAi therapeutic Onpattro in 2018. Since then, a handful of RNAi therapeutics have successfully been approved for use in the clinic, with many more in varying stages of the drug development pipeline. In this context, small interfering RNA (siRNA) has become a highly attractive class of anti-viral modalities with demonstrated efficacy against viruses such as respiratory syncytial virus, Hep B and Hep C viruses. We have identified a promising siRNA that targets a conserved region of the RV genome and knocks out >99% viral infectivity in a cell line. We have also identified siRNA sequences targeting coronavirus.
The challenge now is to optimise delivery of this siRNA to the target tissue/site of viral replication, airway epithelial cells in the respiratory mucosa. Targeted nanoparticles (NP) carrying siRNA molecules are a novel strategy for treating rhinovirus induced diseases We have recently developed novel polymer hybrid nanoparticles able to carry various therapeutic payloads, and these nanoparticles could navigate through the mucus barrier and specifically target the underlying differentiated human airway epithelial cells. We envisage that these nanoparticles will enable efficient delivery of virus RNA targeting siRNAs to the cytoplasm of human airway epithelial cells where the siRNA can engage with the RNA-induced silencing complex (RISC) to specifically degrade viral RNA, halt replication and, in vivo, prevent RV and coronavirus-induced diseases.
PhD Scholarship details
Funding: A generous stipend rate of $40,000 per annum for 4 years. The scholarship will be offered to the successful candidate subject to the grant/funding being fully established
Supervisor: A/Prof Nathan Bartlett
Available to: Domestic students
NSW Health requirements:
(i) is an Australian citizen, permanent resident, or hold an appropriate visa of that provides residency status and right to remain and work in Australia until the later of 30 August 2023 or the projected conclusion of the PhD candidate’s studies; supporting evidence (that is, passport, birth certificate or Australian Citizen Certificate) to be held by Your Organisation and provided to the Agency if requested;
(ii) has an undergraduate degree with at least a credit average or equivalent, and has research experience through an honours program (first class or second class, division one) or Master’s degree by research in a relevant subject and supporting evidence (that is, academic transcripts) to be held by Your Organisation and provided to the Agency if requested.
The applicant will need to meet the minimum University of Newcastle eligibility criteria for admission.
Interested applicants should send an email expressing their interest along with scanned copies of their academic transcripts, CV, a brief statement of their research interests and a proposal that specifically links them to the research project.
Please send the email expressing interest to Nathan.Bartlett@newcastle.edu.au by 5pm on 01 July 2021.
Applications Close 01 July 2021 Apply Now
|Contact||A/Prof Nathan Bartlett|
|Phone||+61 2 4042 0171|
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