Intracerebral delivery of small interfering RNAs (siRNAs) using adenoviral vector protects mice against lethal peripheral rabies challenge

► We investigated RNA interference (RNAi) as antiviral agent against rabies using two small interfering RNAs (siRNAs) targeting rabies virus (RV) nucleoprotein (N) and polymerase (L) genes. ► The antiviral potential of siRNAs delivered using adenoviruses in BHK-21 cells showed marked inhibition in RV multiplication, RV titer knockdown of RV gene transcripts. ► Mice treated with adenoviruses expressing siRNAs showed 66.6% and 33.3% protection with adenoviruses expressing siRNAs against RV-N and RV-L genes, respectively against lethal rabies virus challenge.