RNA-based genetic medicines have enormous potential to transform disease prevention and treatment. However, RNA molecules are very unstable, and the analytical methods available to assess them can’t accurately predict how effective a new genetic medicine will be. A lot of time and money is therefore spent on testing each RNA in labour-intensive functional experiments, slowing drug optimization efforts.
This project titled A Pathogen-ready Arsenal of Next-generation lipid nanoparticle (LNP) messenger RNA (mRNA) therapeutics (PAN-RNA) funded by Genome BC Immunoengineering Strategic Initiative aims to develop two new genetic medicines (for autoimmune disorders and cystic fibrosis), and a comprehensive analytical platform designed to accelerate their development and optimization. We will screen viral genomes to identify sequences that increase RNA stability and expression in specific target cell types, such as lung cells for the cystic fibrosis drug. We will then experimentally assess the functional performance of therapeutic RNAs that incorporate these viral elements. In parallel, we will use advanced imaging-based measurement techniques to comprehensively characterize genetic medicines containing different RNAs. Correlating the resulting data with our functional data on the same RNAs will allow us to develop sophisticated mathematical models that can predict the effectiveness of RNAs using our analytics methods alone, vastly reducing the amount of time and money spent on functional testing.
The immediate outcomes of the project will be two new candidate genetic medicines for further development, a validated analytics platform, and mathematical models to predict genetic medicine performance. However, our work will also serve as proof-of-concept that can be rapidly applied to the development of numerous other genetic medicines. These outcomes will help the biotechnology and pharmaceutical sectors accelerate their genetic medicine development pipelines, ultimately creating new medicines to fight pandemics and help Canadians living with autoimmune disorders, cystic fibrosis, cancer, and other diseases. Our work will also help create new Canadian biotechnology and pharmaceutical industry jobs, companies, and revenue streams, providing additional economic benefits.
The BC-based PAN-RNA project is led by UBC co-directors Eric Jan (Life Sciences Institute, Department of Biochemistry and Molecular Biology) and Sabrina Leslie (Michael Smith Laboratories, Department of Physics). PAN-RNA has assembled a team of expert leaders including Pieter Cullis, a world leader in LNP delivery technology and Laura Evgin, an ECR-expert in CAR-T therapies, Leonard Foster, a proteomics/mass spectrometry expert with extensive experience running a core platform, and collaborators Selena Sagan (molecular virologist), Sarah Hedtrich (lung epithelial gene therapy), Marco Marra (world leader in genomics), and Robin Coope (high-throughput instrumentation). The PAN-RNA project is co-funded by CIHR and NSERC.