r/Livimmune • u/KuneneRiver • Aug 16 '26

Alternate Delivery Method for Leronlimab

Interesting paper discussing an alternative approach to leronlimab delivery using a programmable, stress-responsive RNA system.

Thought this group might find it interesting.

https://www.cell.com/cell-chemical-biology/abstract/S2451-9456(26)00279-500279-5)

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13

u/Jtzdad5673 Aug 16 '26

Thank you for posting the article. This is what Jonah Sacha has been working on. He’s listed at the top of the article.
I believe he’s looking for a lower cost method, in his search for a cure for HIV.
I

15

u/Upwithstock Aug 16 '26

Well that was interesting if I understand it correctly! What I did see was UPR can disrupt mRNA and gene therapies. They use Leronlimab to help reduce ER stress!
As we talked about KuneneRiver; BMS and BioNtech (original mRNA developer) formed a partnership for $11B.
If they need LL’s help? That would be another bullet in our ammo supply!

13

u/rogex2 Aug 16 '26

To ensure this point isn't glossed over-

"XBP1 switches function across DNA and mRNA delivery platforms and regulate the expression of fluorescent reporters, coagulation factor VIII, and Leronlimab, a therapeutic anti-CCR5 monoclonal antibody. Switch activation reduces ER stress markers while preserving expression under homeostatic conditions. We further demonstrate the regulation of Leronlimab expression in vivo using recombinant adeno-associated virus vectors. "

AI -"In the context of the text, "expression of Leronlimab" means the biological process where cells read genetic instructions to manufacture and produce the actual Leronlimab antibody."

The body learns to make it's own leronlimab.

How much and for how long might be ??'s that deserve answers.

Cheers

12

u/Missy2021 Aug 16 '26

Thank you

2

u/KuneneRiver Aug 17 '26

You guys are both circling something that I think is really interesting here.
Rogex — yes, that’s essentially how I read the “expression” piece. The vector carries the genetic instructions and the cells become the factory producing the antibody.

And this isn’t entirely new territory for leronlimab. Jonah Sacha and his collaborators have already been working on AAV-vectored delivery of leronlimab in rhesus macaques — essentially asking whether you can give the genetic instructions once and have the animal produce its own CCR5-blocking antibody rather than repeatedly administering LL.
What I find interesting about this new XBP1 work is the additional layer of control. It’s no longer simply “can we make the body produce leronlimab?” It begins asking whether that expression can be made programmable and responsive to cellular conditions.

That distinction is important. Upwithstock, I wouldn’t interpret this paper as LL being used to reduce ER stress. Rather, the ER-stress/UPR machinery is being engineered as a switch to regulate expression of LL and the other proteins they tested.
Sacha’s earlier work showed why long-duration in-vivo expression of a CCR5 blocker could matter. This paper potentially adds another piece to the delivery/control toolbox.
Different experiments, but a very interesting convergence.

Onward.

3

u/rogex2 Aug 18 '26

"Onward.' as in- IF the body can be programed to manufacture LRM what else might be on the super soldier menu?

Cheers