Hacker News Reader

Comment by w10-1 | Hacker News Reader

Here's the paper: 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).

View on HN

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.”

If you can activate the latent cells all at once, in theory your immune system can do the rest.

"If" is the hard part of many things.

> 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)

Trojan Horse

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.

thank you for this, very interesting

Reply on news.ycombinator.com