As opposed to the RNAi pathway (involving RISC) AUMsilence single-stranded antisense oligonucleotides use RNase H-mediated cleavage (Fig.1). This mode of mRNA knockdown is simpler than siRNA mediated knockdown and eliminates RISC-associated offtarget effects often observed with siRNA. Unlike siRNAs that are processed in the cytoplasm, AUMsilence oligos can go into the nucleus and can be used to target RNA present within the nucleus. Most importantly AUMsilence oligos can be self delivered and do not need transfection reagents or delivery agents.