Lipid-based nanoparticle

Anna Blakeney is an Assistant Professor in the School of Biomedical Engineering and Michael Smith Laboratories at UBC and Canada Research Chair in Nucleic Acid Bioengineering.

Welcome Peter and Anna! we're seeing the rise of RNA therapeutics that rely on LNPs, a drug delivery technology pioneered by Peter.

In this episode, we'll explore why Canada's RNA innovation matters globally, what our country needs to build sovereignty and sustain leadership in this exciting space, and how these advances could transform patient care.

So we are experiencing a true paradigm shift with RNA LNP therapeutics, Peter, could you tell us how far this technology could go?

You see, massive competitors like Pfizer and Alnalam, they love lifelong chronic treatments, right? Daily pills or monthly injections that essentially guarantee them subscription revenue for the rest of a patient's life.

But Intelia? Their absolute moat is their proprietary lipid nanoparticle, or LNP, delivery system.

Think of an LNP like a microscopic, highly targeted delivery truck.

It allows Intelia to deliver a permanent one and done genetic edit directly inside the patient's liver.

And here's the kicker.

And one of the thing which I try to address in my current role is also, I will say that one of the key challenges is that particle size.

So when you are delivering any of the LNP particles or any nanoparticle, it has to travel within the body, and that travel depends on the diffusion rate.

And the diffusion also depends on the size of the particle.

So if you can make a smaller particle, it's going to be much more faster.

It interact with the cell membranes, allow our particles to fuse.

A particle itself becomes a part of the cell membrane, and the cargo directly go to the cytosol, which is different from the LNPs where it mostly end up endosomes, and then you have a endosomal escape, which is not the case in our part of delivery.

[upbeat music] Gene therapy only works if the cargo reaches the right cells intact.

AAV and lipid nanoparticles have carried the field this far.

To get us started, let's start with this perhaps a bit controversial question.

Share something that you believe about bioprocess development that most people disagree with.

In my opinion, bioprocess development is basically coming with the new technologies where like LNPs and AAV are.

It's very complex, and it involves a lot of structural biology informations as well, which is a background about the development of these technology.

To achieve a massive immune response, you have to deliver a massive payload of mRNA, which requires a large dose of lipid nanoparticles.

And those LNPs are inherently reactogenic.

Highly.

They cause systemic inflammation.

When you inject lipid nanoparticles intravenously- They are rapidly opsonized by serum proteins

Specifically apolipoprotein E, according to the research

Yes, which directs the vast majority of the LNPs straight to the liver for clearance

Now, if you are trying to treat liver cancer, that natural tropism is great