Poster Presentation Australia and New Zealand Society for Extracellular Vesicles Conference 2023

A multivalent extracellular vesicle therapy for treating SARS-CoV-2 infection and long COVID (#76)

Paniz Shirmast 1 , Aroon Supramaniam 1 , Adi Idris 2 , Galina Shevchenko 3 , Roslyn Ray 4 , Yaman Tayyar 1 , Nigel McMillan 1 , Kevin Morris 1
  1. Menzies Health Institute Queensland, School of Pharmacy and Medical Science, Griffith University, Gold Coast Campus,, Southport, Queensland, Australia
  2. QUT, School of Biomedical Engineering, Brisbane , Queensland, Australia
  3. Wellcome MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK
  4. CSL Behring, Pasadena, CA, USA

Aims. The EXOtic EV packaging system allows the packaging of RNAs. Brain infection/inflammation due to Long COVID, has been observed in a subset of infected patients, and can potentially be treated using EVs from NSCs, which have been used to treat glioblastoma and inflammation in the brain. In this study, we designed and investigated the potential of asRNA packaged in cell-derived EVs to suppress SARS-COV-2 using EXOtic system.

 

Methods. Several asRNAs targeted to the SARS-CoV-2 viral RNA were screened. asRNA (RdRP CAT as800) found to reproducibly repress the virus. We designed as800 RNA to be packaged with the EXOtic system into EVs from NSCs and checked their anti-inflammatory properties. The CD63-VHH was incorporated with the asRNA and generated anti-SARS-COV-2 EVs-NSCs. The biodistribution of NSC EVs following intranasal and intravenous administration to evaluate the inhibition of SARS-COV-2 in vivo was assessed.

 

Results. We found that addition of CDL7ae binding domain to the end of as800 allows for the packaging in EVs. Also, as800 is capable of repressing SARS-CoV-2 expression. These multivalent EVs were found to significantly neutralize SARS-CoV-2. Also, Nluc-containing NSC EVs disseminate following intranasal administration to the head, stomach, and lung, while the IV-delivered EVs disseminate to liver, spleen, and lungs.

 

Conclusion. NSC-derived exosomes showed that can package asRdRp RNA (Cat 800) and suppress SARS-CoV-2 efficiently. Engineered EVs for SARS-COV-2 suppression can be produced in large quantities and can be engineered to specifically target infected cells, making them an attractive option for the development of clinically useful therapeutic approaches.