Live data from Hacker News

What can mRNA treat next?

qz.com

81–90 of 197 posts

Re: What can mRNA treat next?

#81
post #7

It's an indictment of something that we've had this amazing new tool for vaccine production in existence for a decade but we never even tried to use it for that until COVID because "vaccines typically don’t make much money" and "vaccines just aren’t that exciting" scientifically: "it’s nice and easy," to quote Rossi from the article. If it really does turn out that effective mRNA vaccines can be created in a straight…

This is not new at all. They tried to use mRNA vaccines for other diseases as well, but were never approved. This still holds true to this date. edit: An example would be Dengvaxia.

It seems that Dengvaxia is a live attenuated vaccine, what is the relationship with mRNA vaccine?

Re: What can mRNA treat next?

#82
post #9

Many cancers exhibit immunosuppressive qualities that allow them to co-exist in a healthy immune system. It seems possible that mRNA-based therapies could be used to interfere with those mechanisms (eg binding to PD-L1, etc). The delivery mechanism for the mRNA appears to be the primary innovation and I wonder if it would be possible to target it at specific cells. In the cancer context if you could differentially ta…

I agree. It's easy to overstate things, but over the next several decades I could easily see a computational personalized approach to fighting cancer: read the unique immunosuppressive markers, sort out what's tractable and what's not, then deliver a mRNA payload for that particular cancer for that particular person. For the incredibly small amount that I know, it looks like a game changer. (Like everything else, tho…

Makes you wonder what it would take to get such a process (that produces a new medicine for every individual) approved...

Re: What can mRNA treat next?

#83
post #34

Earlier quoted context omitted.

Or focus on lowering costs. We learned in the pandemic how fundamentally broken the FDA is. There is no reason that things can't be faster that "operation warp speed" all the time. Or re-focus the monetary models around either markets or patient outcomes. Right now, medicine is not a market, it's a strange game. The most money that can be made is finding a treatment that may provide a modest increased benefit over wh…

> There is no reason that things can't be faster that "operation warp speed" all the time. Safety? I'm not wild about new vaccines requiring emergency use authorization and indemnity for the manufacturer. It worked out fine for COVID, but this is not a model I would _want_ to replicate.

The authorization is eua not because of safety concerns but unknown long term efficacy > 1 year. Does this change your assessment?

Re: What can mRNA treat next?

#84

Earlier quoted context omitted.

I agree. It's easy to overstate things, but over the next several decades I could easily see a computational personalized approach to fighting cancer: read the unique immunosuppressive markers, sort out what's tractable and what's not, then deliver a mRNA payload for that particular cancer for that particular person. For the incredibly small amount that I know, it looks like a game changer. (Like everything else, tho…

Makes you wonder what it would take to get such a process (that produces a new medicine for every individual) approved...

The FDA has recently issued draft guidance for such: https://endpts.com/for-tailored-single-person-antisense-olig...

Re: What can mRNA treat next?

#85
post #9

Many cancers exhibit immunosuppressive qualities that allow them to co-exist in a healthy immune system. It seems possible that mRNA-based therapies could be used to interfere with those mechanisms (eg binding to PD-L1, etc). The delivery mechanism for the mRNA appears to be the primary innovation and I wonder if it would be possible to target it at specific cells. In the cancer context if you could differentially ta…

I agree. It's easy to overstate things, but over the next several decades I could easily see a computational personalized approach to fighting cancer: read the unique immunosuppressive markers, sort out what's tractable and what's not, then deliver a mRNA payload for that particular cancer for that particular person. For the incredibly small amount that I know, it looks like a game changer. (Like everything else, tho…

I think this is precisely what BioNTech has been doing with melanoma. Not in a few decades, they already had living patients with personalized vaccination against their own melanomas in 2019:

https://www.nature.com/articles/d41586-019-03072-8

If this immunotherapy gets developed further, the next generations of humanity may look at cancer in the same way that we look upon bacterial diseases: unpleasant, the threat of treatment resistance is there, but not the fearsome serial killer that they used to be.

Re: What can mRNA treat next?

#86
post #7

It's an indictment of something that we've had this amazing new tool for vaccine production in existence for a decade but we never even tried to use it for that until COVID because "vaccines typically don’t make much money" and "vaccines just aren’t that exciting" scientifically: "it’s nice and easy," to quote Rossi from the article. If it really does turn out that effective mRNA vaccines can be created in a straight…

mRNA vaccines have been undergoing active research for decades, and in particular the lipid nanoparticle delivery mechanism used in both the Pfizer and Moderna vaccines was first used in 2018 in a (non-vaccine) drug called Onpattro[2]. Without this technology, Moderna in particular was having issues with excessive side effects as late as 2017[1].

As such, the Covid-19 vaccines from Pfizer/BioNTech and Moderna could not have been developed pre-2018, and - absent a deadly pandemic that requires taking extreme measures (such as using very large trial groups) to hasten the timeline - normally vaccines undergo development over a period of many years[3] to collect sufficient data to ensure effectiveness and to ensure that the long-term side effects are well understood. Moderna in particular was, prior to the Covid-19 pandemic, working on developing vaccines to target cancer using mRNA technology[4]. Had the pandemic not occurred, one would therefore not expect to have seen any approved therapies until the mid-to-late 2020s at the earliest (and probably later, given how often vaccines and other drugs fail in human trials).

In short, the issue was not that pharmaceutical companies were disregarding the technology, so much as simply the last remaining breakthrough needed to be made - and now that mRNA vaccines have proven themselves to be safe and effective, there'll be no shortage of effort to apply them to new diseases.

[1] - https://www.statnews.com/2017/01/10/moderna-trouble-mrna/ [2] - https://www.statnews.com/2020/12/01/how-nanotechnology-helps... [3] - https://www.historyofvaccines.org/content/articles/vaccine-d... [4] - https://www.statnews.com/2017/01/10/moderna-trouble-mrna/

Re: What can mRNA treat next?

#87

mRNA seems almost like a biological programming language; if you can determine how to build a protein that triggers the body's immune system to attack something you want to destroy it's just a matter of design and testing. I wonder if you could build a real language that you could use to design a sequence and automate the testing.

You could, but keep in mind mRNA occurs in 3D and thermodynamic and kinetic forces play a huge role in biochemistry, so it’s quite a bit more complicated than your average program.

Well, that is why it comes 50 years later than, say, Kernighan and Ritchie standard of C.

The know-how and hardware of today are just enough for the 1.0 of mRNA vaccines, so to say. How will the fourth or fifth generation look like, is probably beyond our imagination right now.

Re: What can mRNA treat next?

#88
post #76
post #53

Moderna has a public development pipeline. It shows they are working on, among other things, an HIV vaccine and vaccines/therapies for multiple types of cancer. https://www.modernatx.com/pipeline

HIV is a known virus for many decades. Now that mRNA was released in a rush, why would it suddenly cure HIV?

Now that mRNA is productionized (or at least on the path towards it), and has been used in hundreds of millions of people without apparent major negative short term effects, the barrier is lower for other targets which no longer have to prove the whole technology is safe, effective, and producable.

We have two examples of safe (so far), effective and mass produced mrna vaccines; so it's probably easier to get funding to research and test other targets. HIV is a popular target, although it's also very difficult.

Re: What can mRNA treat next?

#89
post #7

It's an indictment of something that we've had this amazing new tool for vaccine production in existence for a decade but we never even tried to use it for that until COVID because "vaccines typically don’t make much money" and "vaccines just aren’t that exciting" scientifically: "it’s nice and easy," to quote Rossi from the article. If it really does turn out that effective mRNA vaccines can be created in a straight…

We did not have this tool for a decade, it was still very much scientific work in progress, with a lot of practical problems to be solved. Those problems were only ironed out in 2017-2018.

You can absolutely kill or at least maim a new medical technology if you push it on the market too far and a wave of serious side effects hits you. As an example: death of Jesse Gelsinger [0] delayed genetic therapies by several years, possibly a decade or more. Scientists were afraid to touch the tools that killed a young man and produced a public backlash.

[0] https://en.wikipedia.org/wiki/Jesse_Gelsinger

Re: What can mRNA treat next?

#90

Greenlight Biosciences (one of our portfolio companies) is using RNA as a highly targeted-species-specific pesticide.

This honestly is highly concerning - if that can be done for species, the next step could be to target ethnicity. I feel like this is one of those Oppenheimeresque moments in human history.
Post reply on HN