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Next-generation RNA vaccines

Published on August 31, 2025   33 min

Other Talks in the Series: Periodic Reports: Advances in Clinical Interventions and Research Platforms

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0:00
I'm Anna Blakney. I'm an assistant professor at the University of British Columbia in the Michael Smith Laboratories and the School of Biomedical Engineering. Today, I'll be talking to you about next generation RNA vaccines.
0:14
To give you an outline of what I'll talk about today, first, I'll start with state of the field of RNA vaccines and therapies. For those of you who have never heard of self-amplifying RNA, I'll go through an intro to this technology. I'll then talk about my lab's development of novel saRNA vectors and finish off by talking about some of our work on minimizing immunogenicity of lipid nanoparticles.
0:38
One of the priority areas in the field of RNA vaccines and therapies is minimizing the dose of RNA to reduce side effects. Within the past five years, there's been so much progress that has been made for RNA vaccines. We now know from all of the clinical trials and real-world data that's been generated for the safety and efficacy of this platform that the dose of RNA is directly correlated to the frequency and severity of side effects. Thus, minimizing the dose of RNA is required for use of mRNA vaccines in non-pandemic contexts, such as a seasonal influenza vaccine and potentially even more importantly for therapeutic applications.
1:17
How is self-amplifying RNA different from mRNA? One of the ways that we're able to reduce the dose of RNA is by using this saRNA technology. Here I have a typical structure of an mRNA and an saRNA. Starting with the mRNA, you can see that there's a 5' cap and a 3' poly-A tail. There's an untranslated region at either end, at 5' and 3' ends, as well as a gene of interest or antigen in the middle. saRNA has many of the similar structural components, so a 5' cap, a 3' poly-A tail, an untranslated region at either end, and our gene of interest. The main difference you'll notice is these four nsPs are nonstructural proteins. These nonstructural proteins encode a replicase enzyme which enables replication of the RNA once it gets into a patient's cell. I have a very simplified schematic of this process, so you'll notice on the right or the MRNA, once it gets into a cell, it engages with the ribosome and you get translation of your antigen. On off side, saRNA starts out very similarly. Once a copy of saRNA gets into a cell, it engages with the ribosome. You do get some initial translation of the antigen, but more importantly, you get translation of the replicase enzyme. That replicase enzyme then goes back up and re-engages with ribosome and makes exact copies of the saRNA. I have three picture here, but it's actually thousands of copies of the saRNA in a single cell. Because of this, you get much more translation of your antigen. Because of this, we're able to use about 100 times lower dose of saRNA compared to mRNA.

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