Nanoparticle with mRNA appears to prevent, treat peanut allergies in mice

Good news! mRNA keeps on giving!

"Key takeaways

• Peanuts are one of the most common food allergens for children.
• ... scientists have developed a nanoparticle that delivers mRNA to liver cells in order to teach the immune system to tolerate peanut protein and alleviate allergies.
• In mice, the nanoparticle successfully dampened symptoms of serious allergy.
  

... Taking inspiration from COVID-19 vaccines as well as their own research on the disease, they created a first-of-its-kind nanoparticle ... that delivers mRNA to specific cells in the liver. Those cells, in turn, teach the body’s natural defenses to tolerate peanut proteins.

In testing in mice, the nanoparticle not only reversed peanut allergies, but also prevented them from developing. ..."

From the abstract:

"While oral desensitization is capable of alleviating peanut allergen anaphylaxis, long-term immune tolerance is the sought-after goal. We developed a liver-targeting lipid nanoparticle (LNP) platform to deliver mRNA-encoded peanut allergen epitopes to liver sinusoidal endothelial cells (LSECs), which function as robust tolerogenic antigen-presenting cells that induce FoxP3+ regulatory T-cells (Tregs). The mRNA strand was constructed by including nucleotide sequences encoding for nonallergenic MHC-II binding T-cell epitopes, identified in the dominant peanut allergen, Ara h2. These epitopes were inserted in the mRNA strand downstream of an MHC-II targeting sequence, further endowed in vitro with 5′ and 3′ capping sequences, a PolyA tail, and uridine substitution. Codon-optimized mRNA was used for microfluidics synthesis of LNPs with an ionizable cationic lipid, also decorated with a lipid-anchored mannose ligand for LSEC targeting. Biodistribution to the liver was confirmed by in vivo imaging, while ELISpot assays demonstrated an increase in IL-10-producing Tregs in the spleen. Prophylactic administration of tandem-repeat or a combination of encapsulated Ara h2 epitopes induced robust tolerogenic effects in C3H/HeJ mice, sensitized to and subsequently challenged with crude peanut allergen extract. In addition to alleviating physical manifestations of anaphylaxis, there was suppression of Th2-mediated cytokine production, IgE synthesis, and mast cell release, accompanied by increased IL-10 and TGF-β production in the peritoneum. Similar efficacy was demonstrated during LNP administration postsensitization. While nondecorated particles had lesser but significant effects, PolyA/LNP-Man lacked protective effects. These results demonstrate an exciting application of mRNA/LNP for treatment of food allergen anaphylaxis, with the promise to be widely applicable to the allergy field."

Nanoparticle with mRNA appears to prevent, treat peanut allergies in mice | UCLA ... technology could provide platform to fight other allergies, autoimmune disorders

Use of a Liver-Targeting Immune-Tolerogenic mRNA Lipid Nanoparticle Platform to Treat Peanut-Induced Anaphylaxis by Single- and Multiple-Epitope Nucleotide Sequence Delivery (no public access)