5 ms·

Researchers find a way to make the HIV virus visible within white blood cells

216 points by colinprince 1y ago

w10-1 1y ago
Here's the paper: https://www.nature.com/articles/s41467-025-60001-2 https://www.nature.com/articles/s41467-025-60001-2 To be clear: they deliver the HIV TAT protein which activates latent cells to transcribe HIV (ultimately possibly producing viable HIV virions). Activating-to-kill has been pursued with other agents, but none have proven effective at depleting the reservoir. (The latent reservoir requires HIV anti-retroviral therapy to be lifelong, making one of the top three most expensive diseases in the US). This may be more of a proof for the method, of encapsulating a fragile mRNA in a protective lipid layer, but one which will be incorporated into cells. I'd expect it to be used outside attempts to cure HIV (having consumed some HIV funding).
- sirspacey 1y ago
  thank you for this, very interesting
- _Microft 1y ago
  > This may be more of a proof for the method, of encapsulating a fragile mRNA in a protective lipid layer, but one which will be incorporated into cells. I'd expect it to be used outside attempts to cure HIV (having consumed some HIV funding). What does that mean? (mRNA encapsulated in a lipid nanoparticle entering cells is exactly how the COVID vaccines of BioNTech and Moderna work)
  - rusk 1y ago
    Trojan Horse
  - ampdepolymerase 1y ago
    The phospholipid micelles are non-trivial (trade secret) to make and it's the major reason why African nations and other countries have not been able to successfully create mRNA vaccines at scale. A cell is a bundle of proteins wrapped in a membrane that's sort of an oil drop (or as another comment said, a fat bubble). In biology it's called a phospholipid bilayer. Fun fact you can actually "merge" cells together with the help of certain viruses. Drug delivery usually involves moving molecules though this phospholipid bilayer which involves all sorts of tricks. There are pores and receptors on the membrane that can selectively bind to different biochemical molecules and proteins. A good chunk of research in bioinformatics, chemoinformatics, quantum computing is focusing on simulating protein binding dynamics and protein-protein interactions on various levels so we can design drugs that can bind to the receptors we want. (Alphafold made this a lot easier to figure out how to go from a sequence of genetic material to a specific protein shape) A RNA vaccine is kinda like a virus in that it has to be taken into a so the cellular machinery (ribosomes) can build the protein that it codes for. So having a micelle (or nanoparticle, whatever you want to call it) that can get absorbed and merged into the cell that you are targeting specifically is a Big Deal.
- bijection 1y ago
  The linked article covers this - the main innovation is neither the HIV activation treatment nor the general mRNA-wrapped-in-lipids (LNP) delivery mechanism. Instead, it's a new form of LNP which works on specific white blood cells that were hard to target before. It was “previously thought impossible” to deliver mRNA to the type of white blood cell that is home to HIV, said Dr Paula Cevaal, research fellow at the Doherty Institute and co-first author of the study, because those cells did not take up the fat bubbles, or lipid nanoparticles (LNPs), used to carry it. The team have developed a new type of LNP that those cells will accept, known as LNP X. She said: “Our hope is that this new nanoparticle design could be a new pathway to an HIV cure.”
- dyauspitr 1y ago
  If you can activate the latent cells all at once, in theory your immune system can do the rest.
  - ben_w 1y ago
    "If" is the hard part of many things.
bawolff 1y ago
Interesting. I wonder if this would be applicable to other viruses that hide dormant like shingles or herpes.
- hwillis 1y ago
  Unfortunately no, which is a real shame because herpesviruses like EBV are harmful and practically unavoidable. This research is specific to delivering mRNA to white blood cells. Herpesvirus latency is really complicated, more so than HIV. It hides in more tissues and particularly in nerves, which have some degree (debated) of immune privilege. Every type has different latency. Most types have multiple, very different methods of staying latent and stay more latent than HIV. We understand some of those methods, partially understand many of them, and still don't know a lot about others. A latent infection will probably still remain if too few of these pathways are activated at once.
- vikramkr 1y ago
  Always hard to tell what and where specifically the impacts of any research will be. Looking at how they discuss the creating of this lnp formulation in the paper: > We therefore modified the lipid composition of the LNP to enhance potency. First, the ionisable lipid DLin-MC3-DMA (MC3) was replaced with SM-102, an ionisable lipid previously shown to lead to greater cytosolic mRNA delivery through enhanced endosomal escape [30]. Second, the SM-102-LNPs were further modified using ß-sitosterol, a naturally-occurring cholesterol analogue associated with enhanced mRNA delivery [31], to create a formulation referred to as LNP X (Fig. 1b). [30]: https://pubmed.ncbi.nlm.nih.gov/29653760/ https://pubmed.ncbi.nlm.nih.gov/29653760/ [31]: https://pubmed.ncbi.nlm.nih.gov/32080183/ https://pubmed.ncbi.nlm.nih.gov/32080183/ Neither of those papers they cited were focused on HIV/T cells specifically. Maybe this will have no applications, or applications in HIV only, or be generally useful for hard to transfect cells, or be bad for HIV for some unforseen reason but useful elsewhere, or be a dead end, you never know. But yeah maybe if folks run into similar challenges for approaches to dealing with those viruses, maybe there's something from this work that could help them, who knows?
SoftTalker 1y ago
[flagged]
- brokensegue 1y ago
  I don't understand this cynicism. The people who could hypothetically push this forward don't have to be the same people selling prep or other anti-virals
  - SoftTalker 1y ago
    At some point, Eli Lilly or Pfizer or Astra-Zenica or a company like them will have to mass produce and market the drug. They aren't going to kill their golden geese.
    - ebiester 1y ago
      It's game theory in our favor. The team that gets this right suddenly gets 100% of the pie and deals a blow to their competitors, at least until their competitors can find their own path. A five year monopoly on this kind of treatment would be worth more than all the PREP and HIV meds for any one company.
      - altruios 1y ago
        Game theory is not in the peoples' favor. Consider then every other company's game theory: 'go out of business unless... (we stop this research before it is too late and a cure is developed)' which can lead to some dark places. Also: companies do not think like a person thinks. Insolation from consequences, diffuse responsibility, and other mechanisms come into play here.
    - _ihaque 1y ago
      If this (or, more accurately, a drug developed downstream of this technology) worked, they absolutely would. A great example of this in relatively recent history is the treatment of hepatitis C. The treatments pre-circa-2011 were pretty crappy: interferon/ribavirin had poor cure rates and bad side effects. But it was still better than hepatitis destroying your liver, so people dealt with it. Then, in 2011, as the culmination of years of trials, telaprevir (from Vertex/J&J) [1] and boceprevir (Schering-Plough/Merck) [2] were approved and were DRAMATICALLY BETTER than interferon/ribavirin. ...and then just two years later both of these drugs got nuked by the approval of sofosbuvir (aka Sovaldi, from Pharmasset/Gilead) [3], which has _cure_ rates in excess of 90%. Telaprevir and boceprevir were pulled from the market because there was simply no more market for them once sofosbuvir hit. Scientific competition at its finest. There is absolutely a dark side to pharmaceutical pricing and licensing, but please don't let the existence of that dark side cloud your vision of the transformative impact that those of us in biotech R&D want to have (and in many cases, have had). I was at Vertex when the early trial data on telaprevir started coming out and it became clear that we might be able to offer patients real hope who did not have it before. [1] https://en.wikipedia.org/wiki/Telaprevir https://en.wikipedia.org/wiki/Telaprevir [2] https://en.wikipedia.org/wiki/Boceprevir https://en.wikipedia.org/wiki/Boceprevir [3] https://en.wikipedia.org/wiki/Sofosbuvir https://en.wikipedia.org/wiki/Sofosbuvir
istjohn 1y ago
> Prof Tomáš Hanke of the Jenner Institute, University of Oxford, disputed the idea that getting RNA into white blood cells had been a significant challenge. He said the hope that all cells in the body where HIV was hiding could be reached in this way was “merely a dream”.
breppp 1y ago
https://archive.md/Atn11 https://archive.md/Atn11
user____name 1y ago
Another breakthrough earlier last month: https://www.nature.com/articles/s41467-025-59398-7 https://www.nature.com/articles/s41467-025-59398-7
blindriver 1y ago
Pharma companies aren’t incentivized to cure HIV. Gilead found a cure for Hepatitis C but instead of being praised for it, it was derided by Wall Street because the limited financial value. I certainly hope a more honorable company will find a cure instead of a monthly treatment like Ozempic, which is a Wall Street darling because it’s expensive and monthly.
- t-writescode 1y ago
  Human Beings are incentivized to cure HIV. Real people are experiencing real pain and problem to the tune of millions of persons a year. It is among the most stigmatized long-term illnesses on the planet. Maybe BigCo Evil Pharma isn't "incentivized" to cure HIV; but hundreds of universities including those outside the United States, are. The US does not hold a monopoly on medical advancement. HIV is *hard* to cure. That's why it's not been cured yet.
  - pomtato 1y ago
    > Human Beings are incentivized to cure i'm not so sure, insulin for diabetes is a solved problem yet it's costs hundreds of $ all because scumy of pharma corps(looking at you Eli Lily) keep renewing the patent using legal loopholes.
    - kgwxd 1y ago
      ...in the US.
- rzz3 1y ago
  Watch Excision Biotheraputics. I almost guarantee it’ll get bought and killed.
- adrr 1y ago
  Gilead charges $85k for Harvoni. There's also alternative drugs from different manufacturers because there still lots of money to made. Treatments you're constrained by the duration of the patent thats need to be filed before trials. You're looking at a max of 14 years. Ozempic runs out 2032 but there are already alternative drugs.
hackernoops 1y ago
Positive development.
kylehotchkiss 1y ago
Macrophage targeted mRNA. Wonderful. Now do TB & leprosy.
- meindnoch 1y ago
  Leprosy is non-existent in the developed world, and can be cured with antibiotics.
  - jitl 1y ago
    True that it’s preventable if caught early enough in infection. However the nerve damage caused by the leprosy bacteria is much harder to treat and continues the harm even after antibiotic treatment.
  - kylehotchkiss 1y ago
    The developed world is not the only place medicine matters, and the treatment course is months of antibiotics, which not adhering to can lead to antibiotic resistance. So treatment paths that can more deeply/directly eliminate the bacteria without that duration is a worthwhile research target.

216 points by colinprince 1y ago

Here's the paper: https://www.nature.com/articles/s41467-025-60001-2 https://www.nature.com/articles/s41467-025-60001-2 To be clear: they deliver the HIV TAT protein which activates latent cells to transcribe HIV (ultimately possibly producing viable HIV virions). Activating-to-kill has been pursued with other agents, but none have proven effective at depleting the reservoir. (The latent reservoir requires HIV anti-retroviral therapy to be lifelong, making one of the top three most expensive diseases in the US). This may be more of a proof for the method, of encapsulating a fragile mRNA in a protective lipid layer, but one which will be incorporated into cells. I'd expect it to be used outside attempts to cure HIV (having consumed some HIV funding).

sirspacey 1y ago
thank you for this, very interesting
_Microft 1y ago
> This may be more of a proof for the method, of encapsulating a fragile mRNA in a protective lipid layer, but one which will be incorporated into cells. I'd expect it to be used outside attempts to cure HIV (having consumed some HIV funding). What does that mean? (mRNA encapsulated in a lipid nanoparticle entering cells is exactly how the COVID vaccines of BioNTech and Moderna work)
- rusk 1y ago
  Trojan Horse
- ampdepolymerase 1y ago
  The phospholipid micelles are non-trivial (trade secret) to make and it's the major reason why African nations and other countries have not been able to successfully create mRNA vaccines at scale. A cell is a bundle of proteins wrapped in a membrane that's sort of an oil drop (or as another comment said, a fat bubble). In biology it's called a phospholipid bilayer. Fun fact you can actually "merge" cells together with the help of certain viruses. Drug delivery usually involves moving molecules though this phospholipid bilayer which involves all sorts of tricks. There are pores and receptors on the membrane that can selectively bind to different biochemical molecules and proteins. A good chunk of research in bioinformatics, chemoinformatics, quantum computing is focusing on simulating protein binding dynamics and protein-protein interactions on various levels so we can design drugs that can bind to the receptors we want. (Alphafold made this a lot easier to figure out how to go from a sequence of genetic material to a specific protein shape) A RNA vaccine is kinda like a virus in that it has to be taken into a so the cellular machinery (ribosomes) can build the protein that it codes for. So having a micelle (or nanoparticle, whatever you want to call it) that can get absorbed and merged into the cell that you are targeting specifically is a Big Deal.
bijection 1y ago
The linked article covers this - the main innovation is neither the HIV activation treatment nor the general mRNA-wrapped-in-lipids (LNP) delivery mechanism. Instead, it's a new form of LNP which works on specific white blood cells that were hard to target before. It was “previously thought impossible” to deliver mRNA to the type of white blood cell that is home to HIV, said Dr Paula Cevaal, research fellow at the Doherty Institute and co-first author of the study, because those cells did not take up the fat bubbles, or lipid nanoparticles (LNPs), used to carry it. The team have developed a new type of LNP that those cells will accept, known as LNP X. She said: “Our hope is that this new nanoparticle design could be a new pathway to an HIV cure.”
dyauspitr 1y ago
If you can activate the latent cells all at once, in theory your immune system can do the rest.
- ben_w 1y ago
  "If" is the hard part of many things.

bawolff 1y ago

Interesting. I wonder if this would be applicable to other viruses that hide dormant like shingles or herpes.

hwillis 1y ago
Unfortunately no, which is a real shame because herpesviruses like EBV are harmful and practically unavoidable. This research is specific to delivering mRNA to white blood cells. Herpesvirus latency is really complicated, more so than HIV. It hides in more tissues and particularly in nerves, which have some degree (debated) of immune privilege. Every type has different latency. Most types have multiple, very different methods of staying latent and stay more latent than HIV. We understand some of those methods, partially understand many of them, and still don't know a lot about others. A latent infection will probably still remain if too few of these pathways are activated at once.
vikramkr 1y ago
Always hard to tell what and where specifically the impacts of any research will be. Looking at how they discuss the creating of this lnp formulation in the paper: > We therefore modified the lipid composition of the LNP to enhance potency. First, the ionisable lipid DLin-MC3-DMA (MC3) was replaced with SM-102, an ionisable lipid previously shown to lead to greater cytosolic mRNA delivery through enhanced endosomal escape [30]. Second, the SM-102-LNPs were further modified using ß-sitosterol, a naturally-occurring cholesterol analogue associated with enhanced mRNA delivery [31], to create a formulation referred to as LNP X (Fig. 1b). [30]: https://pubmed.ncbi.nlm.nih.gov/29653760/ https://pubmed.ncbi.nlm.nih.gov/29653760/ [31]: https://pubmed.ncbi.nlm.nih.gov/32080183/ https://pubmed.ncbi.nlm.nih.gov/32080183/ Neither of those papers they cited were focused on HIV/T cells specifically. Maybe this will have no applications, or applications in HIV only, or be generally useful for hard to transfect cells, or be bad for HIV for some unforseen reason but useful elsewhere, or be a dead end, you never know. But yeah maybe if folks run into similar challenges for approaches to dealing with those viruses, maybe there's something from this work that could help them, who knows?

SoftTalker 1y ago

[flagged]

brokensegue 1y ago
I don't understand this cynicism. The people who could hypothetically push this forward don't have to be the same people selling prep or other anti-virals
- SoftTalker 1y ago
  At some point, Eli Lilly or Pfizer or Astra-Zenica or a company like them will have to mass produce and market the drug. They aren't going to kill their golden geese.
  - ebiester 1y ago
    It's game theory in our favor. The team that gets this right suddenly gets 100% of the pie and deals a blow to their competitors, at least until their competitors can find their own path. A five year monopoly on this kind of treatment would be worth more than all the PREP and HIV meds for any one company.
    - altruios 1y ago
      Game theory is not in the peoples' favor. Consider then every other company's game theory: 'go out of business unless... (we stop this research before it is too late and a cure is developed)' which can lead to some dark places. Also: companies do not think like a person thinks. Insolation from consequences, diffuse responsibility, and other mechanisms come into play here.
  - _ihaque 1y ago
    If this (or, more accurately, a drug developed downstream of this technology) worked, they absolutely would. A great example of this in relatively recent history is the treatment of hepatitis C. The treatments pre-circa-2011 were pretty crappy: interferon/ribavirin had poor cure rates and bad side effects. But it was still better than hepatitis destroying your liver, so people dealt with it. Then, in 2011, as the culmination of years of trials, telaprevir (from Vertex/J&J) [1] and boceprevir (Schering-Plough/Merck) [2] were approved and were DRAMATICALLY BETTER than interferon/ribavirin. ...and then just two years later both of these drugs got nuked by the approval of sofosbuvir (aka Sovaldi, from Pharmasset/Gilead) [3], which has _cure_ rates in excess of 90%. Telaprevir and boceprevir were pulled from the market because there was simply no more market for them once sofosbuvir hit. Scientific competition at its finest. There is absolutely a dark side to pharmaceutical pricing and licensing, but please don't let the existence of that dark side cloud your vision of the transformative impact that those of us in biotech R&D want to have (and in many cases, have had). I was at Vertex when the early trial data on telaprevir started coming out and it became clear that we might be able to offer patients real hope who did not have it before. [1] https://en.wikipedia.org/wiki/Telaprevir https://en.wikipedia.org/wiki/Telaprevir [2] https://en.wikipedia.org/wiki/Boceprevir https://en.wikipedia.org/wiki/Boceprevir [3] https://en.wikipedia.org/wiki/Sofosbuvir https://en.wikipedia.org/wiki/Sofosbuvir

istjohn 1y ago

> Prof Tomáš Hanke of the Jenner Institute, University of Oxford, disputed the idea that getting RNA into white blood cells had been a significant challenge. He said the hope that all cells in the body where HIV was hiding could be reached in this way was “merely a dream”.

breppp 1y ago

https://archive.md/Atn11 https://archive.md/Atn11

user____name 1y ago

Another breakthrough earlier last month: https://www.nature.com/articles/s41467-025-59398-7 https://www.nature.com/articles/s41467-025-59398-7

blindriver 1y ago

Pharma companies aren’t incentivized to cure HIV. Gilead found a cure for Hepatitis C but instead of being praised for it, it was derided by Wall Street because the limited financial value. I certainly hope a more honorable company will find a cure instead of a monthly treatment like Ozempic, which is a Wall Street darling because it’s expensive and monthly.

t-writescode 1y ago
Human Beings are incentivized to cure HIV. Real people are experiencing real pain and problem to the tune of millions of persons a year. It is among the most stigmatized long-term illnesses on the planet. Maybe BigCo Evil Pharma isn't "incentivized" to cure HIV; but hundreds of universities including those outside the United States, are. The US does not hold a monopoly on medical advancement. HIV is *hard* to cure. That's why it's not been cured yet.
- pomtato 1y ago
  > Human Beings are incentivized to cure i'm not so sure, insulin for diabetes is a solved problem yet it's costs hundreds of $ all because scumy of pharma corps(looking at you Eli Lily) keep renewing the patent using legal loopholes.
  - kgwxd 1y ago
    ...in the US.
rzz3 1y ago
Watch Excision Biotheraputics. I almost guarantee it’ll get bought and killed.
adrr 1y ago
Gilead charges $85k for Harvoni. There's also alternative drugs from different manufacturers because there still lots of money to made. Treatments you're constrained by the duration of the patent thats need to be filed before trials. You're looking at a max of 14 years. Ozempic runs out 2032 but there are already alternative drugs.

hackernoops 1y ago

Positive development.

kylehotchkiss 1y ago

Macrophage targeted mRNA. Wonderful. Now do TB & leprosy.

meindnoch 1y ago
Leprosy is non-existent in the developed world, and can be cured with antibiotics.
- jitl 1y ago
  True that it’s preventable if caught early enough in infection. However the nerve damage caused by the leprosy bacteria is much harder to treat and continues the harm even after antibiotic treatment.
- kylehotchkiss 1y ago
  The developed world is not the only place medicine matters, and the treatment course is months of antibiotics, which not adhering to can lead to antibiotic resistance. So treatment paths that can more deeply/directly eliminate the bacteria without that duration is a worthwhile research target.