However, regarding the treatment of adenoviral infections in immunocompromised patients, CDV is neither capable of fully preventing fatal outcomes in all instances (Lenaerts et al., 2008, Lindemans et al., 2010, Ljungman et al., 2003, Symeonidis et al., 2007 and Yusuf et al., FK228 cost 2006), nor thought to be able to completely clear infections without the concomitant re-establishment of the immune system (Chakrabarti et al., 2002, Heemskerk et al., 2005 and Lindemans et al., 2010). Moreover, it displays significant nephrotoxicity

and limited bioavailability. Derivatives of CDV have been developed, but are still under investigation (Hartline et al., 2005 and Paolino et al., 2011). Thus, there is a need for the development of alternative drugs or even alternative treatment strategies. RNA interference (RNAi) is a post-transcriptional cellular process that results PF-02341066 in vivo in gene silencing (Carthew and Sontheimer, 2009, Ghildiyal and Zamore, 2009, Huntzinger and Izaurralde, 2011, Hutvagner and Simard, 2008 and Kawamata and Tomari, 2010). It is triggered by short (∼21–25 nt) dsRNAs displaying partial or complete complementarity to their target mRNAs (Fire et al., 1998). MicroRNAs (miRNAs) are members of this group of small RNAs. Their precursors, primary miRNAs (pri-miRNAs), are processed by Drosha/DGCR8 into 60–70 nt

precursor miRNAs (pre-miRNAs) (Cullen, 2004), that are subsequently exported from the nucleus by Exportin-5 (Yi et al., 2003), and eventually processed into mature miRNAs by the ribonuclease-III enzyme Dicer (Cullen, 2004). The so-called guide strand is loaded into the RNA-induced silencing complex (RISC) (Sontheimer, 2005),

where it mediates the cleavage or deadenylation of its target mRNA, or leads to translational repression (Huntzinger and Izaurralde, 2011). RNAi has quickly been adopted as a tool to knock down the expression of disease-associated genes or to inhibit check details viral gene expression (Davidson and McCray, 2011). This is either mediated by synthetic short interfering RNAs (siRNAs) that are directly incorporated into RISC (Elbashir et al., 2001), short hairpin shRNAs that resemble pre-miRNAs (Burnett and Rossi, 2012), or artificial miRNAs (amiRNAs) that are analogs of pri-miRNAs (Zeng et al., 2002). RNAi-mediated inhibition of viral replication has been demonstrated for a wide range of viruses, both in vitro and in vivo ( Arbuthnot, 2010, Haasnoot et al., 2007 and Zhou and Rossi, 2011). We and others have recently demonstrated the successful in vitro inhibition of the replication of wild-type (wt) adenovirus (Ad) serotypes 1, 2, 5, and 6 (all belonging to species C and representing a main cause of severe adenovirus-related disease) ( Kneidinger et al., 2012) and a mutated version of Ad5 lacking the E1B and E3 genes ( Eckstein et al., 2010). The inhibition of an Ad 11 strain (2K2/507/KNIH; species B; isolated in Korea) has also been described ( Chung et al., 2007).