Rnai agents for inhibiting expression of synuclein alpha (SNCA), compositions thereof, and methods of use

Abstract

Described are RNAi agents, compositions that include RNAi agents, and methods for inhibition of a synuclein alpha (SNCA) gene. The SNCA RNAi agents and RNAi agent conjugates disclosed herein inhibit the expression of an SNCA gene. The SNCA RNAi agents are conjugated to an antigen binding protein that may enable subcutaneous delivery of the RNAi agents by facilitating crossing of the blood brain barrier (BBB). Pharmaceutical compositions that include one or more SNCA RNAi agents, optionally with one or more additional therapeutics, are also described. Delivery of the described SNCA RNAi agents to central nervous system (CNS) tissue, in vivo, provides for inhibition of SNCA gene expression and a reduction in SNCA activity, which can provide a therapeutic benefit to subjects, including human subjects, for the treatment of various diseases including Parkinson's Disease.