6 ms·

Does anyone know how safe such a thing could be? What keeps the virus from mutating and being dangerous?

toiletfuneral 4y ago
there's a decent history of hijacking viruses for targeted delivery: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4243974/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4243974/
TulliusCicero 4y ago
That's probably why they tend to start these trials with people who are already in medically dire straits. If someone is currently pretty much guaranteed to die -- which is what the eligibility criteria sound like to me, someone correct me if I'm wrong here -- then there's less concern compared to accidentally killing someone who was doing fine before. And those initial trials will let you check for things like virus mutations. They did the same thing with the pig heart transplant recently, did the operation on a guy who desperately needed a new heart but was ineligible for a regular transplant.
- throwaway290 4y ago
  I think jvalencia meant what if the virus transmits between humans for example, and escapes into the wild.
  - sizzle 4y ago
    oh crap, didn't even consider this as a possible 'side effect' I hope someone on HN who has the right scientific background can explain why this is highly unlikely or an impossible outcome..
    - throwaway290 4y ago
      I would presume because flu vaccines etc. require infecting a human with a virus in some form or another, there was plenty of time to ensure engineered viruses do not transmit.
      - rdlw 4y ago
        Is that an accurate comparison? I don't know much about biology so I'm open to be corrected, but I thought that flu vaccines are attenuated or dead versions of the virus, which aren't strong enough to transmit, and RNA vaccines don't include the full virus at all.
        throwaway290 4y ago
        I stand corrected (but FWIW I don't think there's a strong reason for worry unless one is a specialist in this field and has concrete grounds for concern).
      - tragictrash 4y ago
        Flu vaccine does not infect you with the flu. It feeds something that looks like carcasses of the flu virus to your immune system to train it.
        throwaway290 4y ago
        Not quite. 1) There are live adenovirus vaccines currently in use (e.g., https://linkinghub.elsevier.com/retrieve/pii/S0264410X16306168 https://linkinghub.elsevier.com/retrieve/pii/S0264410X163061...). 2) People report being sick from inactivated vaccines so those carcasses you mention evidently still trigger symptoms, and according to Wikipedia "most" viral vectors are designed to be incapable of replication so presumably some could transmit. Additionally, at least with Sputnik botched inactivation had been reported (by Brazil, https://www.dw.com/en/brazil-was-there-sloppiness-with-the-sputnik-v-covid-vaccine/a-57425121 https://www.dw.com/en/brazil-was-there-sloppiness-with-the-s...). Frankly if I get symptoms and am contagious then I will consider myself infected for all intents and purposes. In the end, though, we can engineer non-transmittable viruses if warranted, and with proper care we successfully do so. I don't know the approach taken with the cancer-fighting virus in question but I bet proper care had been taken.
        tragictrash 4y ago
        Great job cherry picking tangentially related info off the internet. Those kind aren't in widespread use for the flu. Technically you aren't incorrect but presenting the information like that is disingenuous.
    - redler 4y ago
      This is almost exactly the premise of “I Am Legend” — the film, at least.
      - riffraff 4y ago
        I think the book deals with a bacteria-based pandemic of unspecified origin. It does have a much, much better plot than the movie tho.
        telesilla 4y ago
        The alternative, book-correct ending apparently failed with test audiences who failed to identify the doctor as the bad guy. https://youtu.be/Bju1srxOYxo https://youtu.be/Bju1srxOYxo
        riffraff 4y ago
        oh, I didn't know that ending existed, thanks! It's been a while since I read the book, but it makes sense to me people failed to identify with the doctor as the bad guy at the end of the movie. In the book, we're shown what amounts to a small love story between him and a vampire, and the living-vampires brutalizing the dead-vampires, and finally the doctor. There's a ton of build up to the reversal that the alt ending does not seem to have.
      - NegativeLatency 4y ago
        “Life always finds a way”
  - kadoban 4y ago
    We're swimming in a sea of viruses. Not sure why we'd expect this one to be any more effective than another.
    - takeda 4y ago
      We have one that we tried to get rid of for 2 years now and we ended up giving up on that.
      - zaarn 4y ago
        We have however developed effective treatment for the infected at this point as well as have a very effective vaccine. If whatever escapes turns out to be worse, I think our response will be much better. Plus remember that we eradicated smallpox entirely.
echelon 4y ago
It's an Orthopoxvirus [1] [2] and is easy to target and kill. We've already eliminated one of the viruses in the family: Smallpox-causing Variola. Also notable, it's a doubly stranded DNA virus, so it will mutate less frequently than other virus families, such as ssDNA and RNA viruses. Patients will undoubtably be monitored closely. That said, we do need to be extremely careful. Wherever it may have originated, Covid should have hopefully instilled caution and respect for safety protocols. [1] https://journals.lww.com/journalacs/Abstract/2020/04000/Novel_Chimeric_Immuno_Oncolytic_Virus.68.aspx https://journals.lww.com/journalacs/Abstract/2020/04000/Nove... [2] https://en.wikipedia.org/wiki/Orthopoxvirus https://en.wikipedia.org/wiki/Orthopoxvirus
- im3w1l 4y ago
  It wouldn't happen to be a monkeypox virus, would it?
  - Brybry 4y ago
    No. CF33 appears to be a chimera of nine viruses: six strains of VACV, cowpox, rabbitpox, and raccoonpox created in monkey cells[1]. Seems to be mostly vaccinia (VACV)[2][3]. [1] https://pubmed.ncbi.nlm.nih.gov/29988502/ https://pubmed.ncbi.nlm.nih.gov/29988502/ page 18 [2] https://www.cell.com/molecular-therapy-family/methods/fulltext/S2329-0501(21)00188-1#tbl1 https://www.cell.com/molecular-therapy-family/methods/fullte... [3] https://www.nature.com/articles/s41417-019-0114-x https://www.nature.com/articles/s41417-019-0114-x
  - echelon 4y ago
    Nice zombie reference. But for those curious, > CF33, and its genetically modified variants (CF33-hNIS-ΔF14.5L and CF33-hNIS-antiPDL1). The creation of CF33 and its sequenced genome has been previously described (11). Briefly, recombination among 9 different species/strains of orthopoxviruses [Cowpox (Brighton), raccoonpox (Herman), rabbitpox (Utrecht), vaccinia virus (Western Reserve), International Health Department, Elstree, and VACV strains Ankara (AS)] resulted in a chimeric orthopoxvirus, CF33, which did not previously exist in nature. This virus has been found to be highly specific for infection, replication within, and killing of breast cancer and pancreatic cancer (11, 12). From https://www.sciencedirect.com/science/article/am/pii/S1072751520301150 https://www.sciencedirect.com/science/article/am/pii/S107275...
flobosg 4y ago
Viral vectors can be genetically engineered to prevent or impair replication.
colechristensen 4y ago
> What keeps the virus from mutating and being dangerous? The large difference between these genetically engineered viruses and ones actively spreading in the wild. They pick and modify them to not spread and get cleared by the immune system and sometimes to include vulnerabilities to treatments.
stubish 4y ago
It is an interesting risk assessment worrying about engineered viruses, when we are literally surrounded by them and any of them could mutate and become dangerous. I have always assumed that an engineered virus specifically engineered to not transcend its limits would be less likely to become a problem than all the other viruses whose ability to mutate around our immune systems is required for them to survive more than a few years. Or is there a factor I'm unaware of, such as the the most useful sources to work from are also the most virulent with nasty behavior just one mutation away from being switched on?
- throw93232 4y ago
  You are assuming good faith from medical industry. Many people do not share that opinion!
sizzle 4y ago
You can ask the creator of vaccinia oncolytic viruses doing an AMA on Reddit here: https://www.reddit.com/r/worldnews/comments/uvplpj/comment/i9n7nbg/ https://www.reddit.com/r/worldnews/comments/uvplpj/comment/i... Let us know if they respond!
JumpCrisscross 4y ago
> What keeps the virus from mutating and being dangerous? Entropy, mostly. We're taking wild type viruses and burdening them with, from their genes' perspective, useless overhead. One would expect them to, on average, tend back towards the wild type. There is always the risk that we stumble them onto a path they wouldn't have found naturally, bump them out of a local optimum, but that's currently hypothetical.
mcswell 4y ago
I don't suppose anything prevents it from doing that, but consider this: Covid19 has infected billions of people. How many times has it mutated? A few hundred, I suppose, with only a few of those mutations having given rise to more infectious variants. That's a few out of billions of cases.
- tragictrash 4y ago
  It's mutated trillions if not quadrillions of times. Most of those died or were inferior and didn't propagate.

there's a decent history of hijacking viruses for targeted delivery: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4243974/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4243974/

TulliusCicero 4y ago

That's probably why they tend to start these trials with people who are already in medically dire straits. If someone is currently pretty much guaranteed to die -- which is what the eligibility criteria sound like to me, someone correct me if I'm wrong here -- then there's less concern compared to accidentally killing someone who was doing fine before. And those initial trials will let you check for things like virus mutations. They did the same thing with the pig heart transplant recently, did the operation on a guy who desperately needed a new heart but was ineligible for a regular transplant.

throwaway290 4y ago
I think jvalencia meant what if the virus transmits between humans for example, and escapes into the wild.
- sizzle 4y ago
  oh crap, didn't even consider this as a possible 'side effect' I hope someone on HN who has the right scientific background can explain why this is highly unlikely or an impossible outcome..
  - throwaway290 4y ago
    I would presume because flu vaccines etc. require infecting a human with a virus in some form or another, there was plenty of time to ensure engineered viruses do not transmit.
    - rdlw 4y ago
      Is that an accurate comparison? I don't know much about biology so I'm open to be corrected, but I thought that flu vaccines are attenuated or dead versions of the virus, which aren't strong enough to transmit, and RNA vaccines don't include the full virus at all.
      - throwaway290 4y ago
        I stand corrected (but FWIW I don't think there's a strong reason for worry unless one is a specialist in this field and has concrete grounds for concern).
    - tragictrash 4y ago
      Flu vaccine does not infect you with the flu. It feeds something that looks like carcasses of the flu virus to your immune system to train it.
      - throwaway290 4y ago
        Not quite. 1) There are live adenovirus vaccines currently in use (e.g., https://linkinghub.elsevier.com/retrieve/pii/S0264410X16306168 https://linkinghub.elsevier.com/retrieve/pii/S0264410X163061...). 2) People report being sick from inactivated vaccines so those carcasses you mention evidently still trigger symptoms, and according to Wikipedia "most" viral vectors are designed to be incapable of replication so presumably some could transmit. Additionally, at least with Sputnik botched inactivation had been reported (by Brazil, https://www.dw.com/en/brazil-was-there-sloppiness-with-the-sputnik-v-covid-vaccine/a-57425121 https://www.dw.com/en/brazil-was-there-sloppiness-with-the-s...). Frankly if I get symptoms and am contagious then I will consider myself infected for all intents and purposes. In the end, though, we can engineer non-transmittable viruses if warranted, and with proper care we successfully do so. I don't know the approach taken with the cancer-fighting virus in question but I bet proper care had been taken.
        tragictrash 4y ago
        Great job cherry picking tangentially related info off the internet. Those kind aren't in widespread use for the flu. Technically you aren't incorrect but presenting the information like that is disingenuous.
  - redler 4y ago
    This is almost exactly the premise of “I Am Legend” — the film, at least.
    - riffraff 4y ago
      I think the book deals with a bacteria-based pandemic of unspecified origin. It does have a much, much better plot than the movie tho.
      - telesilla 4y ago
        The alternative, book-correct ending apparently failed with test audiences who failed to identify the doctor as the bad guy. https://youtu.be/Bju1srxOYxo https://youtu.be/Bju1srxOYxo
        riffraff 4y ago
        oh, I didn't know that ending existed, thanks! It's been a while since I read the book, but it makes sense to me people failed to identify with the doctor as the bad guy at the end of the movie. In the book, we're shown what amounts to a small love story between him and a vampire, and the living-vampires brutalizing the dead-vampires, and finally the doctor. There's a ton of build up to the reversal that the alt ending does not seem to have.
    - NegativeLatency 4y ago
      “Life always finds a way”
- kadoban 4y ago
  We're swimming in a sea of viruses. Not sure why we'd expect this one to be any more effective than another.
  - takeda 4y ago
    We have one that we tried to get rid of for 2 years now and we ended up giving up on that.
    - zaarn 4y ago
      We have however developed effective treatment for the infected at this point as well as have a very effective vaccine. If whatever escapes turns out to be worse, I think our response will be much better. Plus remember that we eradicated smallpox entirely.

echelon 4y ago

It's an Orthopoxvirus [1] [2] and is easy to target and kill. We've already eliminated one of the viruses in the family: Smallpox-causing Variola. Also notable, it's a doubly stranded DNA virus, so it will mutate less frequently than other virus families, such as ssDNA and RNA viruses. Patients will undoubtably be monitored closely. That said, we do need to be extremely careful. Wherever it may have originated, Covid should have hopefully instilled caution and respect for safety protocols. [1] https://journals.lww.com/journalacs/Abstract/2020/04000/Novel_Chimeric_Immuno_Oncolytic_Virus.68.aspx https://journals.lww.com/journalacs/Abstract/2020/04000/Nove... [2] https://en.wikipedia.org/wiki/Orthopoxvirus https://en.wikipedia.org/wiki/Orthopoxvirus

im3w1l 4y ago
It wouldn't happen to be a monkeypox virus, would it?
- Brybry 4y ago
  No. CF33 appears to be a chimera of nine viruses: six strains of VACV, cowpox, rabbitpox, and raccoonpox created in monkey cells[1]. Seems to be mostly vaccinia (VACV)[2][3]. [1] https://pubmed.ncbi.nlm.nih.gov/29988502/ https://pubmed.ncbi.nlm.nih.gov/29988502/ page 18 [2] https://www.cell.com/molecular-therapy-family/methods/fulltext/S2329-0501(21)00188-1#tbl1 https://www.cell.com/molecular-therapy-family/methods/fullte... [3] https://www.nature.com/articles/s41417-019-0114-x https://www.nature.com/articles/s41417-019-0114-x
- echelon 4y ago
  Nice zombie reference. But for those curious, > CF33, and its genetically modified variants (CF33-hNIS-ΔF14.5L and CF33-hNIS-antiPDL1). The creation of CF33 and its sequenced genome has been previously described (11). Briefly, recombination among 9 different species/strains of orthopoxviruses [Cowpox (Brighton), raccoonpox (Herman), rabbitpox (Utrecht), vaccinia virus (Western Reserve), International Health Department, Elstree, and VACV strains Ankara (AS)] resulted in a chimeric orthopoxvirus, CF33, which did not previously exist in nature. This virus has been found to be highly specific for infection, replication within, and killing of breast cancer and pancreatic cancer (11, 12). From https://www.sciencedirect.com/science/article/am/pii/S1072751520301150 https://www.sciencedirect.com/science/article/am/pii/S107275...

flobosg 4y ago

Viral vectors can be genetically engineered to prevent or impair replication.

colechristensen 4y ago

> What keeps the virus from mutating and being dangerous? The large difference between these genetically engineered viruses and ones actively spreading in the wild. They pick and modify them to not spread and get cleared by the immune system and sometimes to include vulnerabilities to treatments.

stubish 4y ago

It is an interesting risk assessment worrying about engineered viruses, when we are literally surrounded by them and any of them could mutate and become dangerous. I have always assumed that an engineered virus specifically engineered to not transcend its limits would be less likely to become a problem than all the other viruses whose ability to mutate around our immune systems is required for them to survive more than a few years. Or is there a factor I'm unaware of, such as the the most useful sources to work from are also the most virulent with nasty behavior just one mutation away from being switched on?

throw93232 4y ago
You are assuming good faith from medical industry. Many people do not share that opinion!

sizzle 4y ago

You can ask the creator of vaccinia oncolytic viruses doing an AMA on Reddit here: https://www.reddit.com/r/worldnews/comments/uvplpj/comment/i9n7nbg/ https://www.reddit.com/r/worldnews/comments/uvplpj/comment/i... Let us know if they respond!

JumpCrisscross 4y ago

> What keeps the virus from mutating and being dangerous? Entropy, mostly. We're taking wild type viruses and burdening them with, from their genes' perspective, useless overhead. One would expect them to, on average, tend back towards the wild type. There is always the risk that we stumble them onto a path they wouldn't have found naturally, bump them out of a local optimum, but that's currently hypothetical.

mcswell 4y ago

I don't suppose anything prevents it from doing that, but consider this: Covid19 has infected billions of people. How many times has it mutated? A few hundred, I suppose, with only a few of those mutations having given rise to more infectious variants. That's a few out of billions of cases.

tragictrash 4y ago
It's mutated trillions if not quadrillions of times. Most of those died or were inferior and didn't propagate.