Lipoplexes targeting mutated PTPN22 gene variant
Autoimmune diseases affect various organs or systems and their incidence is increasing worldwide.
PTPN22 gene encode for the Lyp protein that is involved in the immune system modulation. The PTPN22 C1858T variant is associated to an abnormal Lyp expression and altered immune activity.
In human, the variant has been linked to an increased risk of autoimmune diseases and the people carrying it are 2-4 folds more predisposed to T1D.
Therefore, Lyp modulation represent a valid target to restore the normal immune function.
The invention concerns the creation of lipoplexes that interfere with the C1858T variant in order to bring Lyp expression to normal levels.
The generated lipoplexes are lipid carriers of short RNA molecules (siRNA). The siRNAs, once delivered to the targeted cells, interfere with the C1858T variant reestablishing Lyp levels and thus the normal immune activation.
We proved the lipoplexes efficacy in vitro in down-modulating Lyp expression in peripheral blood cells of T1D patients and monitored in vivo their biodistribution in mice.
Autoimmune diseases associated to C1858T variant:
- TD1, thyroiditis, myasthenia gravis, multiple sclerosis, SLE, Wegener’s granulomatosis, rheumatoid arthritis, juvenile idiopathic arthritis, celiac disease, vitiligo, Sjӧgren syndrome, Addison disease, alopecia, giant cell arteritis, polymyositis.
- The use of our lipoplexes in subjects carrying the variant C1858T can be extended to the prevention/ halt of pathogenesis and ultimately the treatment of autoimmune diseases;
- As regard T1D, in addition to the substitutive insulin administration, the treatment would preserve the residual beta cells and improve the stability of the metabolic course of disease.