mRNA production has fewer dependencies than protein production. To me, it feels reasonably intuitive that this might be a bit faster to assemble, especially at scale and in the face of QC. However, I have a lot of uncertainty around this.
About this next thing, I am more sure. What is more challenging about mRNA, and a good part of why it hadn’t been a major method before, is delivery* into cells, and maybe targeting that delivery (if needed). If they’ve got a great lipid coating already configured for this, at that point it’s easier to treat this like a modifiable platform and not just a single product. And that could help turnaround time a lot.
Being able to treat this as more of a modifiable-platform than a tailored product is where I suspect the big gains of this method lie.
*Delivery method being a major challenge is generally true of all large-molecule drugs and therapeutics (ex: protein-based), and probably even some of the small-molecule ones. Although I’ve seen more and more biotech companies specializing into this kind of thing, so humanity is probably getting better at it.
There’s something almost comical or ironic about immune response probably foiling most attempts to develop something whose eventual goal is to trigger an immune response, but later. But that’s probably a good part of the story of why this was so hard.
P.S. I was about to recommend you make a high-level post about this. I’m glad to see that you already did! I’m probably going to continue a bit of that conversation here, as this seems like a better place for it.
There are many application where targeting the delievery seems important. With vaccines the immune system should pick up the proteins regardles of which cell produces them. There still seems to be some complexity to it as far as the CureVac press briefing indicates. They argued that this is a time where they need to have the founder of the company lead it instead of a rather newish CEO because of the complexity.
Protein origin shouldn’t matter, but mRNAs are not yet proteins. So for mRNA vaccines, they still need a lipid coating for delivery that evades the immune system but will still fuse with cell membranes.
(Normal cell-to-bubble-to-cell delivery involves mostly protein-based tagging and anchoring, and viruses often imitate parts of this process (this is much of what coronavirus spike-proteins are doing, for instance). But if you are using variants of tags that appear unfamiliar to the immune system, you can easily get an immune reaction against them. I’m not precisely sure how these companies have solved this problem, whether it’s by using protein-tagging some entirely-lipid-based solution, or what.)
They might not need to be targeting particular cell-types very heavily, it’s true. But they still need to be targeting for delivery to cells-in-general.
To me the successful CureVac phase I trial for Rabies suggests that they do have a solution for the general targeting.
Given that Moderna is already doing their human trials this month and Biontic next month it seems they also have the problem of delievery to cells-in-general solved.
mRNA production has fewer dependencies than protein production. To me, it feels reasonably intuitive that this might be a bit faster to assemble, especially at scale and in the face of QC. However, I have a lot of uncertainty around this.
About this next thing, I am more sure. What is more challenging about mRNA, and a good part of why it hadn’t been a major method before, is delivery* into cells, and maybe targeting that delivery (if needed). If they’ve got a great lipid coating already configured for this, at that point it’s easier to treat this like a modifiable platform and not just a single product. And that could help turnaround time a lot.
Being able to treat this as more of a modifiable-platform than a tailored product is where I suspect the big gains of this method lie.
*Delivery method being a major challenge is generally true of all large-molecule drugs and therapeutics (ex: protein-based), and probably even some of the small-molecule ones. Although I’ve seen more and more biotech companies specializing into this kind of thing, so humanity is probably getting better at it.
There’s something almost comical or ironic about immune response probably foiling most attempts to develop something whose eventual goal is to trigger an immune response, but later. But that’s probably a good part of the story of why this was so hard.
P.S. I was about to recommend you make a high-level post about this. I’m glad to see that you already did! I’m probably going to continue a bit of that conversation here, as this seems like a better place for it.
There are many application where targeting the delievery seems important. With vaccines the immune system should pick up the proteins regardles of which cell produces them. There still seems to be some complexity to it as far as the CureVac press briefing indicates. They argued that this is a time where they need to have the founder of the company lead it instead of a rather newish CEO because of the complexity.
Protein origin shouldn’t matter, but mRNAs are not yet proteins. So for mRNA vaccines, they still need a lipid coating for delivery that evades the immune system but will still fuse with cell membranes.
(Normal cell-to-bubble-to-cell delivery involves mostly protein-based tagging and anchoring, and viruses often imitate parts of this process (this is much of what coronavirus spike-proteins are doing, for instance). But if you are using variants of tags that appear unfamiliar to the immune system, you can easily get an immune reaction against them. I’m not precisely sure how these companies have solved this problem, whether it’s by using protein-tagging some entirely-lipid-based solution, or what.)
They might not need to be targeting particular cell-types very heavily, it’s true. But they still need to be targeting for delivery to cells-in-general.
To me the successful CureVac phase I trial for Rabies suggests that they do have a solution for the general targeting.
Given that Moderna is already doing their human trials this month and Biontic next month it seems they also have the problem of delievery to cells-in-general solved.