In order to explore the role of TNF-a in Niemann-Pick type C (NPC) disease,lentivi-ral-delivered RNA interference (RNAi) was used to silence the expression of murine TNF-a gene in vitro and in npc mice.Interference efficiency of the lentivirus expressing TNF-a-siRNA,previously constructed with the concentration of 2×108ifu/mL,was determined by RT-PCR and ELISA in BV-2 tricularly infused into 4-week old npc mice for a 4-week period,and the mice were divided into 3 (n=4).By using immunohistochemistry and real-time PCR,the down-regulation of the target genes ciently in vitro and the interference efficiency was 66.7%.Lentivirus could be expressed stably for long-term in the npc mice brain.Immunohistochemistry and real-time PCR revealed that,as com-pard with non-intervention gronp and Lenti-control group,Lenti-TNF-a-siRNA efficiently down-regulated the expression of murine TNF-a gene with the interference efficiency being 66.9%.TNF-a-siRNA downregulated the expression of TNF-a gene in vitro and in vivo,which provided a potential tool for studying and treation neurodegenerative diseases and TNF-a-related diseases.