Antigen‐specific mRNA lipid nanoparticle platforms for the prevention and treatment of allergy and autoimmune diseases

While most nanomedicines primarily aim to stimulate the immune system against infections or tumors, there is a growing demand for inducing immune tolerance under certain conditions, such as allergic and autoimmune diseases. Researchers have explored nanotechnology‐based strategies to induce immune tolerance in a targeted and specific manner. One approach involves the use of nanoparticles (NPs) to encapsulate immunosuppressive drugs and/or antigens to educate naïve T cells and promote the generation of antigen‐specific regulatory T cells that inhibit immune responses. However, this approach has certain limitations. The hydrophobicity of proteins or peptides restricts the degree to which they can be encapsulated in NPs, which in turn, affects their loading efficiency and treatment efficacy. With the emergence of mRNA lipid nanoparticle (LNP) platforms, there is the possibility of overcoming the limitations of protein and peptide encapsulation. To date, mRNA LNP systems have been shown to provide organ, cellular, and subcellular targeting for the induction of immune tolerance. This method of drug delivery is flexible and scalable that can be customized for a specific patient, resulting in an effective means of administering relevant proteins or epitopes to induce antigen‐specific immune tolerance. With continued research and development, this technology could offer a safer and more effective alternative to current therapies, ultimately improving the quality of life of patients worldwide. Lipid nanoparticles (LNPs) are formulated by ionizable cationic lipids (e.g., MC3), helper lipids (e.g., DSPC and cholesterol) and polyethylene glycol (PEG)‐lipids enveloping mRNA molecules and creating inverted micellar structures that protect mRNA from degradation and deliver mRNA to the cytosols for translation. After mRNA LNPs are taken up by antigen‐presenting cells (APCs), the mRNA is released through endosomal escape and translated by ribosomes, synthesizing proteins as antigens. These antigens are presented to the cell surface after post‐translational processing in the endoplasmic reticulum to generate epitopes that are loaded onto MHC‐II molecules and presented on the APC surface. Naïve T cells recognize the epitopes binding to the MHC‐II molecule and differentiate into regulatory T cells that express Foxp3, checkpoint proteins (PD‐1, CTLA‐4, LAG‐3, OX40, etc.), and secrete immunosuppressive cytokines such as TGF‐β, IL‐35, and IL‐10, etc. These regulatory T cells can induce immune tolerance and have the potential to treat allergies and autoimmune diseases such as systemic lupus erythematosus, type I diabetes, and rheumatoid arthritis, etc.