Peanut allergies may be treatable with mRNA-based medicine

“As far as we can find, mRNA has never been used for an allergic disease. We’ve shown that our platform can work to calm peanut allergies, and we believe it may be able to do the same for other allergens, in food and drugs, as well as autoimmune conditions,” said Dr. André Nel, the paper’s co-corresponding author, in a statement. 

For this treatment, they delivered the mRNA inside a nanoparticle to the liver, where it targeted specific cells to tolerate peanut proteins. 

The nanoparticles were tested on mice, which demonstrated that the medicine not only reversed peanut allergies but also prevented the development of severe conditions.

Several trials on mice revealed that the nanoparticle treatment was able to improve the animal’s peanut tolerance. 

According to the authors, with a few more lab studies, the nanoparticle treatment could be ready for clinical trials within three years. Furthermore, the team intends to investigate whether these nanoparticles could be used to treat type 1 diabetes. There is currently only one approved treatment; if this new treatment becomes a reality, it could be a significant advancement in the treatment of peanut allergies in the near future.

The findings were reported in the journal ACS Nano.

Study 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.