In vivo self-assembled siRNAs within small extracellular vesicles attenuate LRRK2-induced neurodegeneration in Parkinson's disease models

• DOI: 10.1016/j.jconrel.2024.12.045
• Publication Date: 2025-01-10T00:21:15Z
• Authors: Li Zhang; Penglu Chen; Tiantian Chen; Lishan Lin; Xiaoyi Ji; Jin Liu; Heng Huang; Tanvikhaa Saravanan; Hannah Fuehrer; Christopher A. Ross; Wanli W. Smith; Zhong Pei; Xi Chen
• Keywords: LRRK2

Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene play an important role Parkinson's disease (PD) pathogenesis, and downregulation of LRRK2 has become a promising therapy for PD. Here, we developed synthetic biology strategy self-assembly delivery small interfering RNAs (siRNAs) into substantia nigra via extracellular vesicles (sEVs) using genetic circuit (in form naked DNA plasmid) to attenuate PD-like phenotypes mouse model.