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).
bijection · 18h 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.”
_Microft · 18h 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 · 18h ago
Trojan Horse
ampdepolymerase · 17h 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.
sirspacey · 18h ago
thank you for this, very interesting
blindriver · 13h 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 · 13h 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.
rzz3 · 7h ago
Watch Excision Biotheraputics. I almost guarantee it’ll get bought and killed.
bawolff · 18h ago
Interesting. I wonder if this would be applicable to other viruses that hide dormant like shingles or herpes.
hwillis · 17h 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.
> 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”.
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).
What does that mean? (mRNA encapsulated in a lipid nanoparticle entering cells is exactly how the COVID vaccines of BioNTech and Moderna work)
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.
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.
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.