Target specific siRNA-conjugate therapy for experimental autoimmune myasthenia gravis

Abstract

Abstract Myasthenia gravis (MG) is an autoimmune disease of muscle weakness caused by Acetylcholine receptor- autoantibody and complement mediated damage of neuro-muscular junction (NMJ). We have recently shown a greater advantage of using siRNA over other conventional therapeutic tools in an experimental mouse model of MG (EAMG). However, the major drawbacks of siRNA therapy is reduced efficacy due to the lack of target restricted delivery, where it is necessary to suppress pathogenic response arising predominantly from a particular cell/tissue type. In this study, we used a novel strategy of cell specific new formulation of siRNA or siRNA conjugate delivery to pathogenic cells in EAMG. Our preliminary work shows successful preparation of siRNA conjugate and its functional efficacy over siRNA only treatment in an in vitro rodent cell line. Successful completion of the study may provide a solution for the siRNA or monoclonal antibody therapy hurdle and a new direction to ultimately explore a highly effective and safe therapy for patients with MG.