IL-2Rβ-tethered IL-2 mRNA-LNP

Interleukin 2 (IL-2) is an interleukin, a cytokine signaling molecule in the immune system, encoded by the IL-2 gene. It is a secreted cytokine that belongs to the IL-2 cytokine subfamily that includes IL-4, IL-7, IL-9, IL-15, IL-21, erythropoietin, and thrombopoietin. IL-2 is a glycoprotein produced by activated CD4+ and CD8+ T lymphocytes and plays an important role in the proliferation of T lymphocytes and B lymphocytes through interactions with a multisubunit receptor complex comprising IL2Rα, IL2Rβ, and IL2Rγ. IL-2 has been implicated in autoimmune diseases, leading to the development of many therapeutic drugs for different autoimmune diseases. Systemic IL-2 supplementation enhances immunity against cancer and viral infections. However, clinical trials have shown that high-dose IL-2 infusion can lead to severe side effects like sepsis, while low-dose IL-2 has a short half-life of efficacy. Based on the fact that adult natural killer (NK) cells only express IL2Rβ and IL2Rγ subunits and are therefore relatively insensitive to IL-2, the fusion protein of IL-2 with its receptor IL-2Rβ, expressed by transfection of NK92 cells, can highly activate the transfected cells without additional exogenous IL-2. Tethering IL-2 to its receptor IL-2Rβ opens up new ways to use IL-2 for immunotherapy. This product is designed as a tool for the delivery and expression of IL-2Rβ-tethered IL-2 mRNA for research. The product leverages the lipid nanoparticle (LNP) technology platform for simple and efficient delivery of IL-2Rβ-tethered IL-2 mRNA to a variety of mammalian cells in vitro and in vivo. The LNPs used are formulated with SM-102, DSPC, cholesterol and DMG-PEG2000 at an optimal molar concentration for a high rate of encapsulation and efficient mRNA delivery. The IL-2-2Rβ fusion protein is approximately 77 kD, consisting of human IL-2 (153 amino acids) and human IL-2Rβ (mature peptide: 525 amino acids) with a GS peptide linker (GGGGSGGGGSGGGGS) in between. The GenPept accession numbers for human IL-2 and IL-2Rβ are NP_000577 and NP_000869 respectively.