In this study we found that siM2 not only decreased the level of M2 mRNA but also the level of NP mRNA, suggesting that siM2 has a broad inhibition manner in the process of influenza virus replication. Ge et al have reported a similar broad inhibition of siRNAs [25] . In their study, NP-1496 and PA-2087 provided a broad inhibition to H1N1 influenza virus, which not only abolished the accumulations of specific NP or PA mRNAs but also inhibited the accumulations of mRNAs for M, NS1, PB1, PB2 and PA or NP genes. A possible explanation is that some double stranded siRNAs may result in IFN responses or activate a RNA degradation pathway, e.g. Phosphorylated protein Kinase R (PKR) [9, 31, 32] . However, the mechanisms of this broad inhibition of some siRNAs are still not very clear yet. From the standpoint of viral target choice in RNAi based antiviral therapy, NP protein is required for elongation and antitermination of nascent cRNA and vRNA transcripts [33, 34] . Without newly synthesized NP, further viral transcription and replication are blocked. While, M2 plays a critical role in the assembly of infectious virus particles. Thus, the potent antiviral effect of siM2 may be attributed to its broad inhibitory effect.